View source for Aging brain

{{short description|Degradation of functioning of the brain}}
[[Aging]] of the [[Human brain|brain]] is a process of transformation of the brain in [[old age|older age]], including changes all individuals experience and those of illness (including unrecognised illness). Usually this refers to humans.

Since [[life extension]] is only pertinent if accompanied by health span extension, and, more importantly, by preserving brain health and cognition, finding rejuvenating approaches that act simultaneously in peripheral tissues and in brain function is a key strategy for development of [[Rejuvenation|rejuvenating]] technology.<ref name="AiB_2023">{{cite journal|last1=Gaspar-Silva|first1=Filipa|last2=Trigo|first2=Diogo|last3=Magalhaes|first3=Joana|title=Ageing in the brain: mechanisms and rejuvenating strategies|date=24 June 2023|journal=[[Cellular and Molecular Life Sciences]]|volume=80|issue=7|page=190|doi=10.1007/s00018-023-04832-6|pmc=10290611|pmid=37354261}}</ref>

Aging is a major risk factor for most common [[neurodegenerative disease]]s, including [[mild cognitive impairment]], [[dementia]]s including [[Alzheimer's disease]], [[cerebrovascular disease]], [[Parkinson's disease]], and [[ALS|Amyotrophic Lateral Sclerosis]].<ref>{{Cite journal |last=Cummings |first=Jeffrey L. |date=2002-05-08 |title=Alzheimer Disease |url=http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.287.18.2335 |journal=JAMA |language=en |volume=287 |issue=18 |pages=2335–2338 |doi=10.1001/jama.287.18.2335 |pmid=11988038 |issn=0098-7484|url-access=subscription }}</ref><ref>{{Cite journal |last1=Winder |first1=Nick R. |last2=Reeve |first2=Emily H. |last3=Walker |first3=Ashley E. |date=2021-01-01 |title=Large artery stiffness and brain health: insights from animal models |journal=American Journal of Physiology. Heart and Circulatory Physiology |language=en |volume=320 |issue=1 |pages=H424–H431 |doi=10.1152/ajpheart.00696.2020 |issn=0363-6135 |pmc=7847068 |pmid=33164578}}</ref> While much research has focused on [[Aging-associated diseases|diseases of aging]], there are few informative studies on the molecular biology of the '''aging brain''' (usually spelled '''ageing brain''' in [[British English]]) in the absence of neurodegenerative disease or the [[Neuropsychology|neuropsychological]] profile of healthy older adults. However, research suggests that the aging process is associated with several structural, chemical, and functional changes in the brain as well as a host of [[Neurocognition|neurocognitive]] changes. Recent reports in [[model organism]]s suggest that as organisms age, there are distinct changes in the [[Gene expression|expression of genes]] at the single [[neuron]] level.<ref>{{cite journal|last1=Kadakkuzha|first1=Beena M|last2=Akhmedov|first2=Komolitdin|title=Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia|journal=BMC Genomics|date=2013-12-14|volume=14|issue=1|page=880|pmid=24330282|doi=10.1186/1471-2164-14-880|pmc=3909179 |doi-access=free }}</ref> This page is an overview of the changes associated with [[human brain]] aging, including [[Senescence#Healthspans and aging in society|aging without concomitant diseases]].

==Structural changes==
[[File:Gehirn, medial - Lobi en.svg|thumb|Human brain in the [[sagittal plane]]]]
[[File:Blausen 0896 Ventricles Brain.png|thumb|[[Ventricular system|Ventricles of the brain]]]]

Aging entails many physical, biological, chemical, and psychological changes and the brain is no exception to this phenomenon. These various changes have attempted to be mapped by [[conceptual model]]s like the Scaffolding Theory of Aging and Cognition (STAC) in 2009. The STAC model looks at factors like neural changes to the [[white matter]], [[dopamine]] depletion, shrinkage, and [[Cerebral cortex|cortical]] thinning.<ref>{{Cite journal |last1=Reuter-Lorenz |first1=Patricia A. |last2=Park |first2=Denise C. |date=2014-09-01 |title=How Does it STAC Up? Revisiting the Scaffolding Theory of Aging and Cognition |journal=Neuropsychology Review |language=en |volume=24 |issue=3 |pages=355–370 |doi=10.1007/s11065-014-9270-9 |issn=1573-6660 |pmc=4150993 |pmid=25143069}}</ref> [[CT scan]]s have found that the [[Ventricular system|cerebral ventricles]] expand as a function of age. More recent [[MRI]] studies have reported age-related regional decreases in cerebral volume.<ref name="Craic">{{cite book |last1=Craik |first1=F. |last2=Salthouse |first2=T. |year=2000 |title=The Handbook of Aging and Cognition |edition=2nd |location=Mahwah, NJ |publisher=Lawrence Erlbaum |isbn=0-8058-2966-0 |oclc=44957002}}</ref><ref name="Raz 2005">{{cite journal |last=Raz |first=Naftali |year=2005 |title=Regional Brain Changes in Aging Healthy Adults: General Trends, Individual Differences and Modifiers |journal=Cerebral Cortex |volume=15 |issue=11 |pages=1676–1689 |pmid=15703252 |doi=10.1093/cercor/bhi044 |display-authors=etal|doi-access=free|hdl=11858/00-001M-0000-0025-8479-B |hdl-access=free }}</ref> Regional volume reduction is not uniform; some brain regions shrink at a rate of up to 1% per year, whereas others remain relatively stable until the end of the life-span.<ref name="Raz 2006">{{cite journal |last1=Raz |first1=Naftali |last2=Rodrigue |first2=Karen M. |year=2006 |title=Differential aging of the brain: Patterns, cognitive correlates and modifiers |journal=Neuroscience & Biobehavioral Reviews |volume=30 |issue=6 |pages=730–748 |pmid=16919333 |pmc=6601348 |doi=10.1016/j.neubiorev.2006.07.001 |url=http://www.rcgd.isr.umich.edu/life/Readings2007/Raz%20reading.pdf |archive-url=https://web.archive.org/web/20110723194504/http://www.rcgd.isr.umich.edu/life/Readings2007/Raz%20reading.pdf |archive-date=July 23, 2011 |access-date=January 28, 2010 }}</ref> The brain is very complex, and is composed of many different areas and types of tissue, or matter. The different functions of different tissues in the brain may be more or less susceptible to age-induced changes.<ref name="Craic"/>  The brain matter can be broadly classified as either grey matter, or white matter. [[Grey matter]] consists of [[cell body|cell bodies]] in the [[Cerebral cortex|cortex]] and [[Basal ganglia|subcortical nuclei]]. [[White matter]] consists of tightly packed [[myelin]]ated [[axon]]s connecting the neurons to each other and with the periphery.<ref name="Craic"/>

===Loss of neural circuits and brain plasticity===
[[Neuroplasticity|Brain plasticity]] refers to the brain's ability to change structure and function.<ref name="Kolb Whishaw 1998">{{cite journal|last1=Kolb|first1=Bryan|title=Brain Plasticity and Behavior|last2=Whishaw|first2=Ian Q.|journal=Annual Review of Psychology|volume=49| issue=1| year=1998| pages=43–64 | doi=10.1146/annurev.psych.49.1.43 |pmid=9496621 |hdl=2027.42/74427|url=https://deepblue.lib.umich.edu/bitstream/2027.42/74427/1/1467-8721.01210.pdf|hdl-access=free}}</ref><ref name="Kolb Gibb 2003">{{cite journal|last1=Kolb| first1=Bryan|last2=Gibb| first2=Robbin|last3=Robinson| first3=Terry E.|title=Brain plasticity and behavior|journal=Current Directions in Psychological Science|volume=12|issue=1|year=2003|pages=1–5|issn=0963-7214|doi=10.1111/1467-8721.01210| hdl=2027.42/74427| s2cid=204347081|url=https://deepblue.lib.umich.edu/bitstream/2027.42/74427/1/1467-8721.01210.pdf|hdl-access=free}}</ref> This ties into the common phrase, "if you don't use it, you lose it," which is another way of saying, if you do not use it, your brain will devote less [[Somatotopic arrangement|somatotopic space]] for it. One proposed mechanism for the observed age-related plasticity deficits in animals is the result of age-induced alterations in [[Calcium metabolism|calcium regulation]].<ref name="Barnes">{{cite journal |last1=Barnes |first1=C. |last2=Burke |first2=S. |year=2006 |title=Neural plasticity in the ageing brain |journal=Nature Reviews Neuroscience |volume=7 |issue=1 |pages=30–40 |doi=10.1038/nrn1809 |pmid=16371948|s2cid=1784238}}</ref>  The changes in the organism's abilities to handle calcium will ultimately influence neuronal firing and the ability to propagate [[action potential]]s, which in turn would affect the ability of the brain to alter its structure or function (i.e. its plastic nature). Due to the complexity of the brain, with all of its structures and functions, it is logical to assume that some areas would be more vulnerable to aging than others. Two circuits worth mentioning here are the [[Hippocampus|hippocampal]] and [[Neocortex|neocortical]] circuits.<ref name="Hof 2004">{{cite journal |vauthors=Hof PR, Morrison JH |title=The aging brain: morphomolecular senescence of cortical circuits |journal=Trends in Neurosciences |volume=27 |issue=10 |pages=607–13 |date=October 2004 |pmid=15374672 |doi=10.1016/j.tins.2004.07.013 |s2cid=31680049}}</ref>  It has been suggested that age-related cognitive decline is due in part not to neuronal death but to [[Synaptic plasticity|synaptic]] alterations. Evidence in support of this idea from animal work has also suggested that this cognitive deficit is due to functional and [[Biochemistry|biochemical]] factors such as changes in [[Enzyme|enzymatic]] activity, chemical messengers, or [[gene expression]] in cortical circuits.<ref name ="Hof 2004"/>

===Thinning of the cortex===
{{Cerebrum labelled map|caption=}}
Advances in MRI technology have provided the ability to see the brain structure in great detail in an easy, non-invasive manner ''[[in vivo]]''. Bartzokis ''et al.'', has noted that there is a decrease in grey matter volume between [[adult]]hood and [[old age]], whereas white matter volume was found to increase from age 19–40, and decline after this age.<ref name="Sowell 2003">{{cite journal |vauthors=Sowell ER, Peterson BS, Thompson PM, Welcome SE, Henkenius AL, Toga AW |title=Mapping cortical change across the human life span |journal=Nature Neuroscience |volume=6 |issue=3 |pages=309–15 |date=March 2003 |pmid=12548289 |doi=10.1038/nn1008 |s2cid=23799692}}</ref> Studies using [[Voxel-based morphometry]] have identified areas such as the [[Insular cortex|insula]] and superior [[Parietal lobe|parietal]] gyri as being especially vulnerable to age-related losses in grey matter of older adults.<ref name="Sowell 2003"/> Sowell ''et al.'', reported that the first 6 decades of an individual's life were correlated with the most rapid decreases in grey matter density, and this occurred over [[Dorsal lobe|dorsal]], [[Frontal lobe|frontal]], and [[Parietal lobe|parietal]] lobes on both [[interhemispheric fissure|interhemispheric]] and lateral brain surfaces. It is also worth noting that areas such as the [[cingulate gyrus]], and [[occipital cortex]] surrounding the [[calcarine sulcus]] appear exempt from this decrease in grey matter density over time.<ref name="Sowell 2003"/>  Age effects on grey matter density in the posterior [[Temporal lobe|temporal cortex]] appear more predominantly in the left versus right hemisphere, and were confined to posterior language cortices. Certain language functions such as word retrieval and production were found to be located to more anterior language cortices, and deteriorate as a function of age. Sowell et al., also reported that these anterior language cortices were found to mature and decline earlier than the more posterior language cortices.<ref name="Sowell 2003"/> It has also been found that the width of [[Sulcus (neuroanatomy)|sulcus]] not only increases with age,<ref>{{cite journal |author1=Tao Liu |author2=Wei Wen |author3=Wanlin Zhu |author4=Julian Trollor |author5=Simone Reppermund |author6=John Crawford |author7=Jesse S Jin |author8=Suhuai Luo |author9=Henry Brodaty |author10=Perminder Sachdev |year=2010 |title=The effects of age and sex on cortical sulci in the elderly |journal=[[NeuroImage]] |volume=51 |issue=1 |pmid=20156569 |doi=10.1016/j.neuroimage.2010.02.016 |pages=19–27|s2cid=8158316}}</ref> but also with cognitive decline in the elderly.<ref>{{cite journal |author1=Tao Liu |author2=Wei Wen |author3=Wanlin Zhu |author4=Nicole A Kochan |author5=Julian N Trollor |author6=Simone Reppermund |author7=Jesse S Jin |author8=Suhuai Luo |author9=Henry Brodaty |author10=Perminder S Sachdev |year=2011 |title=The relationship between cortical sulcal variability and cognitive performance in the elderly |journal=NeuroImage |volume=56 |issue=3 |pages=865–873 |pmid=21397704 |doi=10.1016/j.neuroimage.2011.03.015|s2cid=7489380}}</ref>

===Morphology and microstructure===
{{Expand section|date=March 2023}}

Age-related decrease in gray matter volume was the largest contribution to changes in [[brain volume]]. Moreover, neuronal density appears to decrease, white matter microstructure gets altered and energy metabolism in the [[cerebellum]] gets altered.<ref>{{cite journal |last1=Ding |first1=Xiao-Qi |last2=Maudsley |first2=Andrew A. |last3=Sabati |first3=Mohammad |last4=Sheriff |first4=Sulaiman |last5=Schmitz |first5=Birte |last6=Schütze |first6=Martin |last7=Bronzlik |first7=Paul |last8=Kahl |first8=Kai G. |last9=Lanfermann |first9=Heinrich |title=Physiological neuronal decline in healthy aging human brain — An in vivo study with MRI and short echo-time whole-brain 1H MR spectroscopic imaging |journal=NeuroImage |date=15 August 2016 |volume=137 |pages=45–51 |doi=10.1016/j.neuroimage.2016.05.014 |pmid=27164326 |pmc=4914466 |language=en |issn=1053-8119}}</ref> General cortical atrophy occurs in aging and e.g. the [[caudate nucleus]] volume appears to decrease.<ref>{{cite journal |last1=Pini |first1=Lorenzo |last2=Pievani |first2=Michela |last3=Bocchetta |first3=Martina |last4=Altomare |first4=Daniele |last5=Bosco |first5=Paolo |last6=Cavedo |first6=Enrica |last7=Galluzzi |first7=Samantha |last8=Marizzoni |first8=Moira |last9=Frisoni |first9=Giovanni B. |title=Brain atrophy in Alzheimer's Disease and aging |journal=Ageing Research Reviews |date=1 September 2016 |volume=30 |pages=25–48 |doi=10.1016/j.arr.2016.01.002 |pmid=26827786 |s2cid=42793845 |language=en |issn=1568-1637}}</ref>{{explain|date=March 2023}}

===Age-related neuronal morphology===
There is converging evidence from [[Cognitive neuroscience|cognitive neuroscientists]] around the world that age-induced cognitive deficits may not be due to neuronal loss or cell death, but rather may be the result of small region-specific changes to the [[Morphology (biology)|morphology]] of neurons.<ref name="Barnes"/> Studies by Duan et al., have shown that [[dendritic arbor]]s and [[dendritic spine]]s of [[Cerebral cortex|cortical]] [[pyramidal neuron]]s decrease in size and/or number in specific regions and layers of human and [[non-human primate]] cortex as a result of age (Duan ''et al.'', 2003; morph). A 46% decrease in spine number and spine density has been reported in humans older than 50 compared with younger individuals.<ref name="Hof 2004"/> An [[electron microscopy]] study in [[monkey]]s reported a 50% loss in spines on the [[Apical dendrite|apical dendritic]] tufts of [[pyramidal cell]]s in [[prefrontal cortex]] of old animals (27–32 years old) compared with young ones (6–9 years old).<ref name="Hof 2004"/>

====Neurofibrillary tangles====
[[File:TANGLES HIGH.jpg|thumb|[[Tau protein]] disorders cause [[microtubule]] destruction and formation of [[neurofibrillary tangle]]s.]]

Age-related neuropathologies such as [[Alzheimer's disease]], [[Parkinson's disease]], [[diabetes]], [[hypertension]] and [[arteriosclerosis]] make it difficult to distinguish the normal patterns of aging.<ref name="pmid27045845">{{cite journal |vauthors=Habes M, Janowitz D, Erus G, Toledo JB, Resnick SM, Doshi J, Van der Auwera S, Wittfeld K, Hegenscheid K, Hosten N, Biffar R, Homuth G, Völzke H, Grabe HJ, Hoffmann W, Davatzikos C | title=Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns | journal=[[Translational Psychiatry]] | volume=6 | issue=4 | year=2016 | pages=e775 |  doi=10.1038/tp.2016.39 | pmid=27045845 | pmc=4872397}}</ref><ref name="Gabrieli">{{cite journal |last1=Gabrieli |first1=J. |last2=Hedden |first2=T. |year=2004 |title=Insights into the ageing mind: a view from cognitive neuroscience |journal=Nature Reviews Neuroscience |volume=5 |issue=2 |pages=87–96 |doi=10.1038/nrn1323 |pmid=14735112|s2cid=9398942}}</ref> One of the important differences between normal aging and pathological aging is the location of neurofibrillary tangles.  Neurofibrillary tangles are composed of paired helical filaments (PHF).<ref name="Anderton 2002">{{cite journal |author=Anderton BH |title=Ageing of the brain |journal=Mechanisms of Ageing and Development |volume=123 |issue=7 |pages=811–7 |date=April 2002 |pmid=11869738 |doi=10.1016/S0047-6374(01)00426-2 |s2cid=43097130}}</ref> In normal, non-demented aging, the number of tangles in each affected cell body is relatively low<ref name="Anderton 2002"/> and restricted to the [[Anterior olfactory nucleus|olfactory nucleus]], [[parahippocampal gyrus]], [[amygdala]] and [[entorhinal cortex]].<ref name="Davis 1991">{{cite journal |last1=Davis |first1=P. |last2=Morris |first2=J. |year=1991 |title=The distribution of tangles, plaques, and related immunohistochemical markers in healthy aging and Alzheimer's disease |journal=Neurobiology of Aging |volume=12 |issue=4 |pages=295–312 |pmid=1961359|doi=10.1016/0197-4580(91)90006-6 |s2cid=4060446 |display-authors=etal}}</ref>  As the non-demented individual ages, there is a general increase in the density of tangles, but no significant difference in where tangles are found.<ref name="Davis 1991"/>

The other main neurodegenerative contributor commonly found in the brain of patients with [[Alzheimer's disease|AD]] is [[amyloid plaques]].  However, unlike tangles, plaques have not been found to be a consistent feature of normal aging.<ref name="Davis 1991"/>

===Role of oxidative stress===
{{Main|Oxidative stress}}
[[Cognitive impairment]] has been attributed to oxidative stress, [[Inflammation|inflammatory]] reactions and changes in the cerebral microvasculature.<ref name="Whalley 2004">{{cite journal |vauthors=Whalley LJ, Deary IJ, Appleton CL, Starr JM |title=Cognitive reserve and the neurobiology of cognitive aging |journal=Ageing Research Reviews |volume=3 |issue=4 |pages=369–82 |date=November 2004 |pmid=15541707 |doi=10.1016/j.arr.2004.05.001 |s2cid=6629858}}</ref>  The exact impact of each of these mechanisms in affecting cognitive aging is unknown.  Oxidative stress is the most controllable risk factor and is the best understood.  The online Merriam-Webster Medical Dictionary defines oxidative stress as, "physiological stress on the body that is caused by the cumulative damage done by free radicals inadequately neutralized by [[antioxidant]]s and that is held to be associated with aging."<ref>{{cite web|url=http://www.merriam-webster.com/medical/oxidative_stress |title=Oxidative stress |website=Merriam-Webster Medical dictionary |access-date=24 June 2023}}</ref>  Hence oxidative stress is the damage done to the cells by free radicals that have been released from the oxidation process.{{citation needed|date=November 2024}}

Compared to other tissues in the body, the brain is deemed unusually sensitive to oxidative damage.<ref name="Keller 2005">{{cite journal |vauthors=Keller JN, Schmitt FA, Scheff SW |title=Evidence of increased oxidative damage in subjects with mild cognitive impairment |journal=Neurology |volume=64 |issue=7 |pages=1152–6 |date=April 2005 |pmid=15824339 |doi=10.1212/01.WNL.0000156156.13641.BA |s2cid=398262 |url=http://www.chem.uky.edu/research/butterfield/dab_pdfs/Keller%20et%20al%202005%20Neurology%2064%201152-1156.pdf |display-authors=etal }}</ref> Increased oxidative damage has been associated with neurodegenerative diseases, mild [[cognitive impairment]] and individual differences in cognition in healthy elderly people.  In 'normal aging', the brain is undergoing oxidative stress in a multitude of ways.  The main contributors include protein oxidation, [[lipid peroxidation]] and oxidative modifications in [[Nuclear DNA|nuclear]] and [[Mitochondrial DNA|mitochondrial]] DNA.<ref name="Keller 2005"/>  Oxidative stress can damage [[DNA replication]] and inhibit [[DNA repair|repair]] through many complex processes, including [[telomere#Shortening|telomere shortening]] in DNA components.<ref name="Harris 2006">{{cite journal |vauthors=Harris SE, Deary IJ, MacIntyre A |title=The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people |journal=Neuroscience Letters |volume=406 |issue=3 |pages=260–4 |date=October 2006 |pmid=16919874 |doi=10.1016/j.neulet.2006.07.055|s2cid=24592571 |display-authors=etal}}</ref>  Each time a [[somatic cell]] replicates, the telomeric DNA component shortens.  As telomere length is partly inheritable,<ref name="Harris 2006"/> there are individual differences in the age of onset of cognitive decline.

===DNA damage===
At least 25 studies have demonstrated that [[DNA repair#DNA damage|DNA damage]] accumulates with age in the mammalian brain.  This DNA damage includes the oxidized nucleoside 8-hydroxydeoxyguanosine (8-OHdG), single- and double-strand breaks, DNA-protein [[cross-link]]s and [[malondialdehyde]] [[adduct]]s (reviewed in Bernstein et al.<ref>Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K. (2008) Cancer and aging as consequences of un-repaired DNA damage. In: ''New Research on DNA Damage'' (Editors: Honoka Kimura And Aoi Suzuki) [[Nova Science Publishers, Inc.]], New York, Chapter 1, pp. 1-47. see pg. 18. {{ISBN|978-1-60456-581-2}}</ref>).  Increasing DNA damage with age has been reported in the brains of the mouse, rat, gerbil, rabbit, dog, and human.  Young 4-day-old rats have about 3,000 single-strand breaks and 156 double-strand breaks per neuron, whereas in rats older than 2 years the level of damage increases to about 7,400 single-strand breaks and 600 double-strand breaks per neuron.<ref>{{cite journal |vauthors=Mandavilli BS, Rao KS | year = 1996 | title = Accumulation of DNA damage in aging neurons occurs through a mechanism other than apoptosis | journal = J Neurochem | volume = 67 | issue = 4| pages = 1559–65 | pmid = 8858940 | doi = 10.1046/j.1471-4159.1996.67041559.x | s2cid = 42442582}}</ref>

Lu et al.<ref name="Lu 2004">{{cite journal |vauthors=Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA | year = 2004 | title = Gene regulation and DNA damage in the ageing human brain | journal = Nature | volume = 429 | issue = 6994| pages = 883–891 | doi = 10.1038/nature02661 | pmid = 15190254 | bibcode = 2004Natur.429..883L | s2cid = 1867993}}</ref> studied the [[Transcription (biology)|transcriptional]] profiles of the human [[frontal cortex]] of individuals ranging from 26 to 106 years of age. This led to the identification of a set of genes whose [[Gene expression|expression]] was altered after age 40.  They further found that the [[Promoter (genetics)|promoter]] sequences of these particular genes accumulated oxidative DNA damage, including 8-OHdG, with age (see [[DNA damage theory of aging]]).  They concluded that DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a pattern of brain aging that starts early in life.{{citation needed|date=November 2024}}

== Immune system and fluids ==
{{Expand section|date=March 2023}}
{{See also|#Inflammation|Inflammaging}}
[[Blood–brain barrier]] permeability, [[neuroinflammation]] and [[Neurodegenerative disease|neurodegeneration]], and [[gut microbiota]]-induced [[Systemic inflammation|systemic chronic inflammation]] appear to be linked and interact with aging, e.g. as gut microbiota [[homeostasis]] could be disturbed by increasing age.<ref>{{cite journal |last1=Mou |first1=Yi |last2=Du |first2=Yu |last3=Zhou |first3=Lixing |last4=Yue |first4=Jirong |last5=Hu |first5=Xianliang |last6=Liu |first6=Yixin |last7=Chen |first7=Sao |last8=Lin |first8=Xiufang |last9=Zhang |first9=Gongchang |last10=Xiao |first10=Hengyi |last11=Dong |first11=Birong |title=Gut Microbiota Interact With the Brain Through Systemic Chronic Inflammation: Implications on Neuroinflammation, Neurodegeneration, and Aging |journal=Frontiers in Immunology |date=2022 |volume=13 |article-number=796288 |doi=10.3389/fimmu.2022.796288 |pmid=35464431 |pmc=9021448 |issn=1664-3224|doi-access=free}}</ref> According to a review, neuroinflammatory changes, "including [[microglia]]l activation and production of [[inflammatory cytokine]]s", occur with normal aging.<ref>{{cite journal |last1=Yin |first1=Fei |last2=Sancheti |first2=Harsh |last3=Patil |first3=Ishan |last4=Cadenas |first4=Enrique |title=Energy metabolism and inflammation in brain aging and Alzheimer's disease |journal=Free Radical Biology and Medicine |date=1 November 2016 |volume=100 |pages=108–122 |doi=10.1016/j.freeradbiomed.2016.04.200 |pmid=27154981 |pmc=5094909 |language=en |issn=0891-5849}}</ref>{{explain|date=March 2023}}

===Fluids===
{{See also|#Cerebrospinal fluid}}
[[Cerebral blood flow]] was shown to decrease 0.3-0.5% per year in healthy ageing.<ref>{{cite journal |last1=Graff |first1=Barnaby J. |last2=Harrison |first2=Stephanie L. |last3=Payne |first3=Stephen J. |last4=El-Bouri |first4=Wahbi K. |title=Regional Cerebral Blood Flow Changes in Healthy Ageing and Alzheimer's Disease: A Narrative Review |journal=Cerebrovascular Diseases |date=2023 |volume=52 |issue=1 |pages=11–20 |doi=10.1159/000524797 |pmid=35640565 |s2cid=249236311 |language=english |issn=1015-9770|doi-access=free }}</ref> An efficiently functioning [[glymphatic system]], involved in waste clearance, may be important for maintaining brain health and its transport efficiency appears to be declining with aging.<ref>{{cite journal |last1=Benveniste |first1=Helene |last2=Liu |first2=Xiaodan |last3=Koundal |first3=Sunil |last4=Sanggaard |first4=Simon |last5=Lee |first5=Hedok |last6=Wardlaw |first6=Joanna |title=The Glymphatic System and Waste Clearance with Brain Aging: A Review |journal=Gerontology |date=2019 |volume=65 |issue=2 |pages=106–119 |doi=10.1159/000490349 |pmid=29996134 |pmc=6329683 |language=english |issn=0304-324X}}</ref> Factors in the circulation have been shown to modulate ageing and to rejuvenate the brain.<ref>{{cite journal |last1=Wyss-Coray |first1=Tony |title=Ageing, neurodegeneration and brain rejuvenation |journal=Nature |date=November 2016 |volume=539 |issue=7628 |pages=180–186 |doi=10.1038/nature20411 |pmid=27830812 |pmc=5172605 |bibcode=2016Natur.539..180W |language=en |issn=1476-4687}}</ref>{{explain|date=March 2023}}

== Chemical changes ==
[[File:Dopamine pathways.svg|thumb|230px|Major dopamine pathways.<br />As part of the [[Mesolimbic pathway|reward pathway]], dopamine is manufactured in nerve cell bodies located within [[Ventral tegmental area|VTA]] and is released in the [[nucleus accumbens]] and the [[prefrontal cortex]]. The motor functions of dopamine are linked to a separate pathway, with cell bodies in the [[substantia nigra]] that manufacture and release dopamine into the [[striatum]].|alt=A labelled line drawing of dopamine pathways superimposed on a drawing of the human brain.]]
[[File:Dopamine and serotonin pathways.png|thumb|230px|Dopamine and serotonin functions and pathways]]

In addition to the structural changes that the brain incurs with age, the aging process also entails a broad range of biochemical changes. More specifically, neurons communicate with each other via specialized chemical messengers called [[neurotransmitter]]s. Several studies have identified a number of these neurotransmitters, as well as their [[Receptor (biochemistry)|receptors]], that exhibit a marked alteration in different regions of the brain as part of the normal aging process.{{citation needed|date=November 2024}}

=== Dopamine ===
An overwhelming number of studies have reported age-related changes in [[dopamine]] synthesis, [[binding site]]s, and number of [[Receptor (biochemistry)|receptors]].  Studies using [[positron emission tomography]] (PET) in living human subjects have shown a significant age-related decline in dopamine synthesis,<ref name="Hof 2009">{{cite book |author1=Mobbs, Charles V. |author2=Hof, Patrick R. |title=Handbook of the neuroscience of aging |publisher=Elsevier/Academic Press |location=Amsterdam |year=2009 |isbn=978-0-12-374898-0 |oclc=299710911}}</ref> notably in the [[striatum]] and [[extrastriate cortex|extrastriatal]] regions (excluding the [[midbrain]]).<ref>{{cite journal |last1=Ota |first1=M. |last2=Yasuno |first2=F. |last3=Ito |first3=H. |last4=Seki |first4=C. |last5=Kozaki |first5=S. |last6=Asada |first6=T. |last7=Suhara |first7=T. |year=2006 |title=Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[β-<sup>11</sup>C]DOPA |journal=Life Sciences |volume=79 |issue=8 |pages=730–736 |doi=10.1016/j.lfs.2006.02.017 |pmid=16580023}}</ref>  Significant age-related decreases in dopamine receptors [[Dopamine receptor D1|D<sub>1</sub>]], [[Dopamine receptor D2|D<sub>2</sub>]], and [[Dopamine receptor D3|D<sub>3</sub>]] have also been highly reported.<ref name="Kaasinen 2000">{{cite journal |last1=Kaasinen |first1=V. |last2=Vilkman |first2=H. |last3=Hietala |first3=J. |last4=Någren |first4=K. |last5=Helenius |first5=H. |last6=Olsson |first6=H. |last7=Farde |first7=L. |last8=Rinne |first8=J. O. |year=2000 |title=Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain |journal=Neurobiology of Aging |volume=21 |issue=5 |pages=683–688 |pmid=11016537 |doi=10.1016/S0197-4580(00)00149-4 |s2cid=40871554}}</ref><ref name="Wang 1998">{{cite journal |vauthors=Wang Y, Chan GL, Holden JE |title=Age-dependent decline of dopamine D1 receptors in human brain: a PET study |journal=Synapse |volume=30 |issue=1 |pages=56–61 |date=September 1998 |pmid=9704881 |doi=10.1002/(SICI)1098-2396(199809)30:1<56::AID-SYN7>3.0.CO;2-J |s2cid=31445572 |display-authors=etal}}</ref><ref name="Iyo 1993">{{cite journal |last1=Iyo |first1=M. |last2=Yamasaki |first2=T. |year=1993 |title=The detection of age-related decrease of dopamine, D1, D2 and serotonin 5-HT2 receptors in living human brain |journal=Progress in Neuro-Psychopharmacology and Biological Psychiatry |volume=17 |issue= 3|pages=415–421 |doi=10.1016/0278-5846(93)90075-4 |pmid=8475323 |s2cid=20933930}}</ref><ref name="Rinne 1989">{{cite journal |first1=Juha O. |last1=Rinne |first2=Pirkko |last2=Lonnberg |first3=Paivi |last3=Marjamaiki |year=1989 |title=Age-dependent decline in human brain dopamine D1 and D2 receptors |journal=Brain Research |volume=508 |issue= 2|pages=349–352 |doi= 10.1016/0006-8993(90)90423-9|pmid=2407314 |s2cid=39023717}}</ref><ref name="Wong 1984">{{cite journal |last=Wong |first=D. F. |year=1984 |title=Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain |journal=[[Science (journal)|Science]] |volume=226 |issue=4681 |pages=1393–1396 |doi=10.1126/science.6334363 |pmid=6334363|display-authors=etal|bibcode=1984Sci...226.1393W |s2cid=24278577}}</ref>  A general decrease in D<sub>1</sub> and D<sub>2</sub> receptors has been shown,<ref name="Iyo 1993"/> and more specifically a decrease of D<sub>1</sub> and D<sub>2</sub> receptor binding in the [[caudate nucleus]] and [[putamen]].<ref name="Wang 1998"/><ref name="Wong 1984"/>  A general decrease in D<sub>1</sub> receptor density has also been shown to occur with age.  Significant age-related declines in dopamine receptors, D<sub>2</sub> and D<sub>3</sub> were detected in the [[anterior cingulate cortex]], [[frontal cortex]], lateral [[temporal cortex]], [[hippocampus]], medial temporal cortex, [[amygdala]], medial [[thalamus]], and lateral thalamus.<ref name="Kaasinen 2000"/> One study also indicated a significant inverse correlation between dopamine binding in the [[occipital cortex]] and age.<ref name="Wang 1998"/>  [[Postmortem studies]] also show that the number of D<sub>1</sub> and D<sub>2</sub> receptors decline with age in both the [[caudate nucleus]] and the [[putamen]], although the ratio of these receptors did not show age-related changes.<ref name="Rinne 1989"/> The loss of dopamine with age is thought to be responsible for many neurological symptoms that increase in frequency with age, such as decreased arm swing and increased [[Rigidity (psychology)|rigidity]].<ref name="Wang Snyder 1998">{{cite book |last1=Wang |first1=E. |last2=Snyder |first2=S. D. |year=1998 |title=Handbook of the aging brain |location=San Diego, California |publisher=Academic Press |isbn=0-12-734610-4 |oclc=636693117}}</ref> Changes in dopamine levels may also cause age-related changes in [[cognitive flexibility]].<ref name="Wang Snyder 1998"/>

===Serotonin===
{{See also|Serotonin}}
Decreasing levels of different [[serotonin receptor]]s and the [[serotonin transporter]] (5-HTT), have also been shown to occur with age. Studies conducted using [[positron emission tomography|PET]] methods on humans, in vivo, show that levels of the [[5-HT2 receptor|5-HT<sub>2</sub> receptor]] in the [[caudate nucleus]], [[putamen]], and frontal cerebral cortex, decline with age.<ref name="Wong 1984"/>  A decreased binding capacity of the 5-HT<sub>2</sub> receptor in the frontal cortex was also found,<ref name="Iyo 1993"/> as well as a decreased binding capacity of the serotonin transporter (5-HHT) in the [[thalamus]] and the [[midbrain]].<ref>{{cite journal |last1=Yamamoto |first1=M. |last2=Suhara |first2=T. |last3=Okubo |first3=Y. |last4=Ichimiya |first4=T. |last5=Sudo |first5=Y. |last6=Inoue |first6=Y. |last7=Takano |first7=A. |last8=Yasuno |first8=F. |last9=Yoshikawa |first9=K. |last10=Tanada |first10=S. |year=2001 |title=Age-related decline of serotonin transporters in living human brain of healthy males |journal=Life Sciences |volume=71 |issue= 7|pages=751–757 |doi= 10.1016/S0024-3205(02)01745-9|pmid=12074934}}</ref>  Postmortem studies on humans have indicated decreased binding capacities of serotonin and a decrease in the number of S<sub>1</sub> receptors in the frontal cortex and [[hippocampus]] as well as a decrease in [[Binding affinity|affinity]] in the [[putamen]].<ref>{{cite journal |last1=Marcusson |first1=J. |last2=Oreland |first2=L. |last3=Winblad |first3=B. |year=1984 |title=Effect of age on human brain serotonin (S-1) binding sites |journal=[[Journal of Neurochemistry]] |volume=43 |issue=6 |pages=1699–1705 |pmid=6491674 |doi=10.1111/j.1471-4159.1984.tb06098.x |s2cid=36750403}}</ref>

===Glutamate===
[[File:Glutamate reuptake via EAAT2 (GLT1).jpg|thumb|230px|Expression of [[glutamate transporter 1]] in [[glial cell]] facilitates reuptake of glutamate and decreases extracellular glutamate concentration]]

[[Glutamate]] is another [[neurotransmitter]] that tends to decrease with age.<ref name="Chang 2009">{{cite journal |vauthors=Chang L, Jiang CS, Ernst T |title=Effects of age and sex on brain glutamate and other metabolites |journal=Magnetic Resonance Imaging |volume=27 |issue=1 |pages=142–5 |date=January 2009 |pmid=18687554 |pmc=3164853 |doi=10.1016/j.mri.2008.06.002}}</ref><ref name="Sailasuta 2008">{{cite journal |vauthors=Sailasuta N, Ernst T, Chang L |title=Regional variations and the effects of age and gender on glutamate concentrations in the human brain |journal=Magnetic Resonance Imaging |volume=26 |issue=5 |pages=667–75 |date=June 2008 |pmid=17692491 |pmc=2712610 |doi=10.1016/j.mri.2007.06.007}}</ref><ref name="Kaiser 2005">{{cite journal |vauthors=Kaiser LG, Schuff N, Cashdollar N, Weiner MW |title=Age-related glutamate and glutamine concentration changes in normal human brain: 1H MR spectroscopy study at 4 T |journal=Neurobiology of Aging |volume=26 |issue=5 |pages=665–72 |date=May 2005 |pmid=15708441 |pmc=2443746 |doi=10.1016/j.neurobiolaging.2004.07.001}}</ref>  Studies have shown older subjects to have lower glutamate concentration in the [[motor cortex]] compared to younger subjects.<ref name="Kaiser 2005"/> A significant age-related decline especially in the [[Parietal lobe|parietal]] gray matter, [[basal ganglia]], and to a lesser degree, the [[Frontal lobe|frontal]] white matter, has also been noted.<ref name="Chang 2009"/><ref name="Sailasuta 2008"/> Although these levels were studied in the normal human brain, the parietal and basal ganglia regions are often affected in degenerative brain diseases associated with aging and it has therefore been suggested that brain glutamate may be useful as a [[Biomarker|marker]] of brain diseases that are affected by aging.<ref name="Chang 2009"/>

==Neuropsychological changes==
===Changes in orientation===
[[Orientation (mental)|Orientation]] is defined as the awareness of self in relation to one's surroundings.<ref name="Lezak">{{cite book |last1=Lezak |first1=M.D |last2=Howieson |first2=D.B. |last3=Loring |first3=D.W. |year=2004 |title=Neuropsychological Assessment |edition=4th |location=Oxford |publisher=Oxford University Press |isbn=978-0-19-511121-7}}</ref> Often orientation is examined by distinguishing whether a person has a sense of time, place, and person. Deficits in orientation are one of the most common symptoms of brain disease, hence tests of orientation are included in almost all medical and [[Neuropsychology|neuropsychological]] evaluations.<ref name="Alverzo 2006">{{cite journal |author =Alverzo JP |title=A review of the literature on orientation as an indicator of level of consciousness |journal=Journal of Nursing Scholarship |volume=38 |issue=2 |pages=159–164 |year=2006 |pmid=16773920 |doi=10.1111/j.1547-5069.2006.00094.x}}</ref> While research has primarily focused on levels of orientation among clinical populations, a small number of studies have examined whether there is a normal decline in orientation among healthy aging adults.  Results have been somewhat inconclusive. Some studies suggest that orientation does not decline over the lifespan.<ref name="Brotchie">{{cite journal |last1=Brotchie |first1=J. |last2=Brennan |first2=J.|last3=Wyke |first3=M.|year=1985 |title=Temporal orientation in the presenium and old age. |journal=British Journal of Psychiatry |volume=147 |issue=6 |pages=692–695 |doi=10.1192/bjp.147.6.692|pmid=3830331 |s2cid=28550165}}</ref><ref name="Hopp">{{cite journal |last1=Hopp |first1=G.A. |last2=Dixon |first2=R.A. |last3=Grut |first3=M. |last4=Bacekman |first4=L. |year=1997 |title=Longitudinal and psychometric profiles of two cognitive status tests in very old adults. |journal=Journal of Clinical Psychology |volume=53 |issue=7 |pages=673–686 |doi=10.1002/(sici)1097-4679(199711)53:7<673::aid-jclp5>3.0.co;2-j|pmid=9356897}}</ref> For example, in one study 92% of normal elderly adults (65–84 years) presented with perfect or near perfect orientation.<ref name="Benton">{{cite journal |last1=Benton |first1=A.L. |last2=Eslinger |first2=P. |last3=Damasio |first3=A. |year=1981 |title=Normative observations on neuropsychological test performances in old age. |journal=Journal of Clinical Neuropsychology |volume=3 |issue=1 |pages=33–42 |doi=10.1080/01688638108403111|pmid=7276195}}</ref> However some data suggest that mild changes in orientation may be a normal part of aging.<ref name="Ishizaki">{{cite journal |last1=Ishizaki |first1=J. |last2=Meguro |first2=K. |last3=Ambo |first3=H. |last4=Shimada |first4=M. |last5=Yamaguchi |first5=S. |last6=Harasaka |first6=C. |year=1998 |title=A normative community based study of mini-mental state in elderly adults: The effect of age and educational level. |journal=The Journals of Gerontology: Series B |volume=53 |issue=6 |pages=359–363 |doi=10.1093/geronb/53b.6.p359 |pmid=9826967 |display-authors=etal|doi-access=free}}</ref><ref name="Sweet">{{cite journal |last1=Sweet |first1=J.J. |last2=Such |first2=Y. |last3=Leahy |first3=B. |last4=Abramowitz |first4 = C. |last5=Nowinski |first5=C.J. |year=1999 |title=Normative clinical relationships between orientation and memory: Age as an important moderator variable. |journal=The Clinical Neuropsychologist |volume=13 |issue=4 |pages=495–508 |doi=10.1076/1385-4046(199911)13:04;1-y;ft495|pmid=10806463}}</ref> For example, Sweet and colleagues concluded that "older persons with normal, healthy memory may have mild orientation difficulties. In contrast, younger people with normal memory have virtually no orientation problems"<ref name="Sweet"/> (p.&nbsp;505). So although current research suggests that normal aging is not usually associated with significant declines in orientation, mild difficulties may be a part of normal aging and not necessarily a sign of a particular pathology.{{citation needed|date=November 2024}}

===Changes in attention===
Many older adults notice a decline in their attentional abilities.<ref name="Kensinger">{{cite book |last=Kensinger |first=E.A |year=2009 |title=Cognition in aging and age related disease. In P. R. Hof & C. V. Mobbs (Eds.), Handbook of the neuroscience of aging (249-256). |location=London |publisher=Elsevier Press}}</ref> [[Attention]] is a broad construct that refers to "the cognitive ability that allows us to deal with the inherent processing limitations of the human brain by selecting information for further processing".<ref name="Banich">{{cite book |last1=Banich |first1=M. T. |last2=Compton |first2=R. J. |year=2011 |title=Cognitive neuroscience |location=Belmont, CA |publisher=Wadsworth |page=334}}</ref> Since the human brain has limited resources, people use their attention to zone in on specific stimuli and block out others.{{citation needed|date=November 2024}}

If older adults have fewer attentional resources than younger adults, we would expect that when two tasks must be carried out at the same time, older adults' performance will decline more than that of younger adults. However, a large review of studies on cognition and aging suggest that this hypothesis has not been wholly supported.<ref name="Light">{{cite journal |last=Light |first=L.L. |year=1991 |title=Memory and aging: Four hypotheses in search of data |journal=Annual Review of Psychology |volume=42 |pages=333–376 |doi=10.1146/annurev.ps.42.020191.002001 |pmid=2018397}}</ref> While some studies have found that older adults have a more difficult time encoding and retrieving information when their attention is divided, other studies have not found meaningful differences from younger adults. Similarly, one might expect older adults to do poorly on tasks of sustained attention, which measure the ability to attend to and respond to stimuli for an extended period of time. However, studies suggest that sustained attention shows no decline with age. Results suggest that sustained attention increases in early adulthood and then remains relatively stable, at least to the middle of the eighth decade of life.<ref name="Carriere">{{cite journal |last1=Carrier |first1=J. S. A. |last2=Cheyne |first2=A. |last3=Solman |first3=G. J. F. |last4=Smilek |first4=D. |year=2010 |title=Age trends for failures of sustained attention |journal=Psychology and Aging |volume=25 |issue=3 |pages=569–574| doi=10.1037/a0019363 | pmid=20677878}}</ref> More research is needed on how normal aging impacts attention after age eighty.{{citation needed|date=November 2024}}

It is worth noting that there are factors other than true attentional abilities that might relate to difficulty paying attention. For example, it is possible that [[Sensory neuron|sensory]] deficits impact older adults' attentional abilities. In other words, impaired hearing or vision may make it more difficult for older adults to do well on tasks of visual and verbal attention.<ref name="Kensinger"/>

=== Changes in memory ===
{{Main|Memory and aging}}
Many different types of memory have been identified in humans, such as [[declarative memory]] (including [[episodic memory]] and [[semantic memory]]), [[working memory]], [[spatial memory]], and [[procedural memory]].<ref name="Craic"/> Studies done, have found that memory functions, more specifically those associated with the [[medial temporal lobe]] are especially vulnerable to age-related decline.<ref name="Hof 2004"/> A number of studies utilizing a variety of methods such as [[Histology|histological]], structural imaging, [[functional imaging]], and [[receptor binding]] have supplied converging evidence that the [[frontal lobe]]s and frontal-striatal [[dopaminergic pathways]] are especially affected by age-related processes resulting in memory changes.<ref name="Craic"/>

=== Changes in language ===
Changes in performance on verbal tasks, as well as the location, extent, and signal intensity of [[Blood-oxygen-level-dependent imaging|BOLD]] signal changes measured with [[functional MRI]], vary in predictable patterns with age.  For example, behavioral changes associated with age include compromised performance on tasks related to word retrieval, comprehension of sentences with high syntactic and/or [[working memory]] demands, and production of such sentences.<ref>Crosson, B., Garcia, A., Mcgregor, K., & Wierenga, C. E. (2013). The Impact of Aging on Neural Systems for Language. In M. F. G. Sandra Koffler, Joel Morgan, Ida Sue Baron (Ed.), Neuropsychology, Volume 1 (pp. 149–187). Oxford University Press. {{ISBN|9780199794317}}</ref>

=== Brain activation patterns ===
The left [[inferior frontal junction]] and left anterior [[cuneus]]/[[precuneus]] were the only regions in a larger set of regions associated with [[executive functions]], that consistently showed age differences in brain activity.<ref>{{cite journal |last1=Heckner |first1=Marisa K. |last2=Cieslik |first2=Edna C. |last3=Eickhoff |first3=Simon B. |last4=Camilleri |first4=Julia A. |last5=Hoffstaedter |first5=Felix |last6=Langner |first6=Robert |title=The Aging Brain and Executive Functions Revisited: Implications from Meta-analytic and Functional-Connectivity Evidence |journal=Journal of Cognitive Neuroscience |date=1 August 2021 |volume=33 |issue=9 |pages=1716–1752 |doi=10.1162/jocn_a_01616|pmid=32762523 |pmc=8630425 |biorxiv=10.1101/2020.07.15.204941}}</ref>

=== Changes in learning and behavioral flexibility ===
{{See also|#Loss of neural circuits and brain plasticity|Learning#Adult learning vs children's learning}}
Learning is often [[Development of the nervous system in humans|more efficient in children]] and takes longer or is more difficult with age. A study using [[neuroimaging]] identified rapid [[neurotransmitter]] [[Γ-Aminobutyric acid|GABA]] boosting as a major potential explanation-component for why that is.<ref>{{cite news |title=Brain scans shed light on how kids learn faster than adults |url=https://www.upi.com/Science_News/2022/11/17/brain-scans-children-learn/9721668697147/ |access-date=17 December 2022 |work=UPI |language=en}}</ref><ref>{{cite journal |last1=Frank |first1=Sebastian M. |last2=Becker |first2=Markus |last3=Qi |first3=Andrea |last4=Geiger |first4=Patricia |last5=Frank |first5=Ulrike I. |last6=Rosedahl |first6=Luke A. |last7=Malloni |first7=Wilhelm M. |last8=Sasaki |first8=Yuka |last9=Greenlee |first9=Mark W. |last10=Watanabe |first10=Takeo |title=Efficient learning in children with rapid GABA boosting during and after training |journal=Current Biology |date=5 December 2022 |volume=32 |issue=23 |pages=5022–5030.e7 |doi=10.1016/j.cub.2022.10.021 |pmid=36384138 |language=English |issn=0960-9822|biorxiv=10.1101/2022.01.02.474022|s2cid=253571891|doi-access=free |bibcode=2022CBio...32E5022F }}</ref>

Behavioral flexibility can refer to efficiently and appropriately adapting to different situations and changing environmental demands, including the speed of adaptation, and to the capacity to develop solutions to novel problems or novel solutions to old problems.<ref name="10.1038/s41583-021-00428-w">{{cite journal |last1=Uddin |first1=Lucina Q. |title=Cognitive and behavioural flexibility: neural mechanisms and clinical considerations |journal=Nature Reviews Neuroscience |date=March 2021 |volume=22 |issue=3 |pages=167–179 |doi=10.1038/s41583-021-00428-w |pmid=33536614 |pmc=7856857 |language=en |issn=1471-0048}}</ref><ref>{{cite journal |last1=Audet |first1=Jean-Nicolas |last2=Lefebvre |first2=Louis |title=What's flexible in behavioral flexibility? |journal=Behavioral Ecology |date=1 August 2017 |volume=28 |issue=4 |pages=943–947 |doi=10.1093/beheco/arx007|doi-access=free }}</ref> Studies indicate late-stage aging, and/or late-life dementias,<ref name="10.1038/s41583-021-00428-w"/> decreases behavioral flexibility and impair deliberation about courses of action.<ref>{{cite journal |last1=Breton |first1=Yannick-André |last2=Seeland |first2=Kelsey D. |last3=Redish |first3=A. David |title=Aging impairs deliberation and behavioral flexibility in inter-temporal choice |journal=Frontiers in Aging Neuroscience |date=2015 |volume=7 |page=41 |doi=10.3389/fnagi.2015.00041 |pmid=25870560 |pmc=4375985 |issn=1663-4365|doi-access=free}}</ref><ref>{{cite journal |last1=Yang |first1=Wenzhong |last2=Zhou |first2=Xueyan |last3=Ma |first3=Tao |title=Memory Decline and Behavioral Inflexibility in Aged Mice Are Correlated With Dysregulation of Protein Synthesis Capacity |journal=Frontiers in Aging Neuroscience |date=2019 |volume=11 |article-number=246 |doi=10.3389/fnagi.2019.00246 |pmid=31551760 |pmc=6737270 |issn=1663-4365|doi-access=free}}</ref>

== Genetic changes ==
{{Further|Genetics of aging}}
Variation in the effects of aging among individuals can be attributed to both genetic, health, and [[environmental factor]]s. As in so many other science disciplines, the [[nature versus nurture]] debate is an ongoing conflict in the field of [[cognitive neuroscience]].<ref name="Gabrieli"/><ref name="Anderton 2002"/> The search for genetic factors has always been an important aspect in trying to understand [[Neuropathology|neuropathological]] processes. Research focused on discovering the genetic component in developing Autosomal Dominant (AD) has also contributed greatly to the understanding the genetics behind normal or "non-pathological" aging.<ref name="Anderton 2002"/>

: Autosomal Dominant (AD) - Autosomal dominant is a pattern of inheritance characteristic of some genetic disorders. "[[Autosome|Autosomal]]" means that the gene in question is located on one of the numbered, or non-sex, chromosomes. "[[Dominance (genetics)|Dominant]]" means that a single copy of the mutated gene (from one parent) is enough to cause the disorder.

The human brain shows a decline in function and a change in [[gene expression]]. This modulation in gene expression may be due to [[oxidative]] [[DNA damage]] at [[Promoter (genetics)|promoter]] regions in the genome.<ref name="Lu 2004"/>  Genes that are down-regulated over the age of 40 include:{{citation needed|date=November 2024}}

* GluR1 [[AMPA receptor]] [[Protein subunit|subunit]]
* [[NMDA R2A receptor subunit]] (involved in [[memory|learning]])
* Subunits of the [[GABA A receptor|GABA-A receptor]]
* Genes involved in [[long-term potentiation]] e.g. [[calmodulin]] 1 and [[CaM Kinase II]] alpha
* [[Calcium signaling]] genes
* [[Synaptic plasticity]] genes
* [[Synaptic vesicle]] release and recycling genes

Genes that are upregulated include:{{citation needed|date=November 2024}}

* Genes associated with [[stress response]] and [[DNA repair]]
* [[Antioxidant]] defence

== Measurement ==
===Epigenetic age analysis of brain regions===
The [[cerebellum]] is the youngest brain region (and probably body part) in centenarians according to an epigenetic [[biomarker]] of tissue age known as [[epigenetic clock]]: it is about 15 years younger than expected in a centenarian.<ref name="Horvath2015cerebellum">{{Cite journal| title = The cerebellum ages slowly according to the epigenetic clock. | journal = Aging| volume = 7 | year = 2015| url = https://www.aging-us.com/article/100742/text | pmid = 26000617  |pmc= 4468311|vauthors=Horvath S, Mah V, Lu AT, Woo JS, Choi OW, Jasinska AJ, Riancho JA, Tung S, Coles NS, Braun J, Vinters HV, Coles LS | issue = 5 | doi=10.18632/aging.100742 | pages=294–306}}</ref> By contrast, all brain regions and brain cells appear to have roughly the same epigenetic age in subjects who are younger than 80.<ref name="Horvath2015cerebellum"/><ref name="Horvath2013">{{cite journal | author=Horvath S | title=DNA methylation age of human tissues and cell types | journal=[[Genome Biology]]  | volume=14 | issue=10 | year=2013 | pages=R115  | article-number=3156 | pmc = 4015143 |pmid=24138928 | doi=10.1186/gb-2013-14-10-r115 | doi-access=free }}{{Erratum|doi=10.1186/s13059-015-0649-6|pmid=25968125|http://retractionwatch.com/2015/06/15/high-profile-aging-paper-posts-old-erratum-requested-by-author-more-than-one-year-prior/ ''Retraction Watch''|doi-access=free}}</ref> These findings suggest that the cerebellum is better protected from aging effects, which in turn could explain why the cerebellum exhibits fewer neuropathological hallmarks of age related dementias compared to other brain regions.{{citation needed|date=November 2024}}

===Other===
There is research and development of [[biomarkers of aging]], detection systems and software systems to measure biological age of the brain. For example, a [[deep learning]] software using anatomic [[Magnetic resonance imaging|magnetic resonance images]] estimated brain age with relatively high accuracy, including detecting early signs of [[Alzheimer's disease]] and varying [[Neuroanatomy|neuroanatomical]] patterns of [[Neurological disorder|neurological]] aging.<ref>{{cite journal |last1=Yin |first1=Chenzhong |last2=Imms |first2=Phoebe |last3=Cheng |first3=Mingxi |display-authors=et al. |title=Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment |journal=Proceedings of the National Academy of Sciences |date=10 January 2023 |volume=120 |issue=2 |article-number=e2214634120 |doi=10.1073/pnas.2214634120 |doi-access=free |pmid=36595679 |pmc=9926270 |bibcode=2023PNAS..12014634Y |language=en |issn=0027-8424 }}
* University press release: {{cite news |title=How old is your brain, really? AI-powered analysis accurately reflects risk of cognitive decline and Alzheimer's disease |url=https://medicalxpress.com/news/2023-01-brain-ai-powered-analysis-accurately-cognitive.html |access-date=17 February 2023 |work=University of Southern California via medicalxpress.com |language=en |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232042/https://medicalxpress.com/news/2023-01-brain-ai-powered-analysis-accurately-cognitive.html |url-status=live}}
* News article about the study: {{cite news |title=KI kann wahres Alter des Hirns bestimmen |url=https://www.deutschlandfunknova.de/nachrichten/alterungsprozess-ki-kann-wahres-alter-des-hirns-bestimmen |access-date=17 February 2023 |work=[[Deutschlandfunk Nova]] |language=de |archive-date=17 February 2023 |archive-url=https://web.archive.org/web/20230217232037/https://www.deutschlandfunknova.de/nachrichten/alterungsprozess-ki-kann-wahres-alter-des-hirns-bestimmen |url-status=live}}</ref>

==Delaying the effects of aging==
{{Further|Neuroenhancement|Life extension#Strategies}}
{{See also|Development of the nervous system in humans#Adult neural development}}
The current state of [[biomedical technology]] does not allow to stop and reverse aging. However, one may potentially delay the effects and severity of its symptoms.
While there is no [[Scientific consensus|consensus]] of efficacy, the following are reported as delaying cognitive decline:
* High level of education<ref name="Anderton 2002"/><ref name="Scarmeas 2003">{{cite journal |last1=Scarmeas |first1=N. |last2=Stern |first2=Y. |year=2003 |title=Cognitive reserve and lifestyle |journal=Journal of Clinical and Experimental Neuropsychology |volume=25 |issue=5 |pages=625–633 |doi=10.1076/jcen.25.5.625.14576 |pmid=12815500 |pmc=3024591}}</ref>
* [[Neurobiological effects of physical exercise|Physical exercise]]<ref name="Baker">{{cite journal |last1=Baker |first1=L.D. |last2= Frank |first2=L.L. |last3=Foster-Schubert |first3=K. |last4=Green |first4=P.S. |last5=Wilinson |first5=C.W. |last6=McTiernan |first6=A. |year=2010 |title= Effects of aerobic exercise on mile cognitive impairment: A controlled trial |journal= Archives of Neurology |volume= 67 |pages= 71–79 |issue=1|doi=10.1001/archneurol.2009.307|display-authors=etal|pmc=3056436 |pmid=20065132}}</ref><ref name="10.3233/JAD-201462"/><ref name="10.1016/j.cmet.2018.05.011"/>
* Staying intellectually engaged, i.e. reading and mental activities (such as crossword puzzles)<ref name="Hall">{{cite journal |last1=Hall |first1=C.B. |last2= Lipton |first2= R. B. |last3=Sliwinski |first3= M. |last4=Katz |first4=M. J. |last5= Derby |first5=C. A. |last6= Verghese |first6=J. |year=2009 |title= Cognitive activities delay onset of memory decline in persons who develop dementia |journal= Neurology |volume=73 |issue=5 |pages= 356–361 |doi=10.1212/wnl.0b013e3181b04ae3|pmc=2725932 |pmid=19652139}}</ref><ref name="10.3233/JAD-201462"/>
* Maintaining social and friendship networks<ref name="Barnes2">{{cite journal |last1=Barnes |first1=L. L. |last2=Mendes de Leon |first2=C.F. |last3=Wilson |first3= R. S. |last4= Bienias |first4= J. L. |author4-link = Julia Bienias |last5 = Evans |first5= D. A. |year=2004 |title=Social resources and cognitive decline in a population of older African Americans and whites |journal=Neurology |volume=63 |issue=12 |pages=2322–2326 |doi=10.1212/01.wnl.0000147473.04043.b3|pmid=15623694 |s2cid=30469207}}</ref><ref name="10.3233/JAD-201462">{{cite journal |last1=Krivanek |first1=Taylor J. |last2=Gale |first2=Seth A. |last3=McFeeley |first3=Brittany M. |last4=Nicastri |first4=Casey M. |last5=Daffner |first5=Kirk R. |title=Promoting Successful Cognitive Aging: A Ten-Year Update |journal=Journal of Alzheimer's Disease |date=1 January 2021 |volume=81 |issue=3 |pages=871–920 |doi=10.3233/JAD-201462 |pmid=33935078 |pmc=8293659 |language=en |issn=1387-2877}}</ref>
* Maintaining a [[healthy diet]], including [[omega-3 fatty acid]]s,<ref>{{cite journal |last1=Chappus-McCendie |first1=Hillary |last2=Chevalier |first2=Laurie |last3=Roberge |first3=Claude |last4=Plourde |first4=Mélanie |title=Omega-3 PUFA metabolism and brain modifications during aging |journal=Progress in Neuro-Psychopharmacology and Biological Psychiatry |date=30 August 2019 |volume=94 |article-number=109662 |doi=10.1016/j.pnpbp.2019.109662 |pmid=31152862 |hdl=11143/15833 |s2cid=169031411 |language=en |issn=0278-5846|hdl-access=free }}</ref><ref>{{cite journal |last1=Dyall |first1=Simon C. |title=Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA |journal=Frontiers in Aging Neuroscience |date=2015 |volume=7 |page=52 |doi=10.3389/fnagi.2015.00052 |pmid=25954194 |pmc=4404917 |issn=1663-4365|doi-access=free}}</ref><ref>{{cite journal |last1=Denis |first1=Isabelle |last2=Potier |first2=Brigitte |last3=Heberden |first3=Christine |last4=Vancassel |first4=Sylvie |title=Omega-3 polyunsaturated fatty acids and brain aging |journal=Current Opinion in Clinical Nutrition & Metabolic Care |date=March 2015 |volume=18 |issue=2 |pages=139–146 |doi=10.1097/MCO.0000000000000141 |pmid=25501348 |s2cid=205780791 |issn=1363-1950}}</ref> protective [[antioxidant]]s<ref name="Gabrieli"/> and e.g. [[flavonol]]s-containing foods<ref>{{cite journal |last1=Holland |first1=Thomas Monroe |last2=Agarwal |first2=Puja |last3=Wang |first3=Yamin |last4=Dhana |first4=Klodian |last5=Leurgans |first5=Sue E. |last6=Shea |first6=Kyla |last7=Booth |first7=Sarah L. |last8=Rajan |first8=Kumar |last9=Schneider |first9=Julie A. |last10=Barnes |first10=Lisa L. |title=Association of Dietary Intake of Flavonols With Changes in Global Cognition and Several Cognitive Abilities |journal=Neurology |date=22 November 2022 |volume=100 |issue=7 |article-number=e694–e702 |doi=10.1212/WNL.0000000000201541 |pmid=36414424 |pmc=9969915 |s2cid=253800625 |language=en |issn=0028-3878|url=https://todayspractitioner.com/wp-content/uploads/2022/11/FlavonolsDementia-Study.pdf}}</ref> as well as potentially [[anthocyanin]]s- and [[flavanone]]s-containing ones<ref>{{cite journal |last1=Gardener |first1=Samantha L. |last2=Rainey-Smith |first2=Stephanie R. |last3=Weinborn |first3=Michael |last4=Bondonno |first4=Catherine P. |last5=Martins |first5=Ralph N. |title=Intake of Products Containing Anthocyanins, Flavanols, and Flavanones, and Cognitive Function: A Narrative Review |journal=Frontiers in Aging Neuroscience |date=3 September 2021 |volume=13 |article-number=640381 |doi=10.3389/fnagi.2021.640381|pmid=34539375 |pmc=8446387 |doi-access=free}}</ref><ref>{{cite journal |last1=Kent |first1=K. |last2=Charlton |first2=K. E. |last3=Netzel |first3=M. |last4=Fanning |first4=K. |title=Food-based anthocyanin intake and cognitive outcomes in human intervention trials: a systematic review |journal=Journal of Human Nutrition and Dietetics |date=June 2017 |volume=30 |issue=3 |pages=260–274 |doi=10.1111/jhn.12431|pmid=27730693 |s2cid=4344504}}</ref> as in, more generally, [[Mediterranean diet]] patterns<ref>{{cite journal |last1=Di Giosia |first1=Paolo |last2=Stamerra |first2=Cosimo Andrea |last3=Giorgini |first3=Paolo |last4=Jamialahamdi |first4=Tannaz |last5=Butler |first5=Alexandra E. |last6=Sahebkar |first6=Amirhossein |title=The role of nutrition in inflammaging |journal=Ageing Research Reviews |date=May 2022 |volume=77 |article-number=101596 |doi=10.1016/j.arr.2022.101596|pmid=35219904 |s2cid=247087388}}</ref><ref>{{cite journal |last1=Moore |first1=Katie |last2=Hughes |first2=Catherine F. |last3=Ward |first3=Mary |last4=Hoey |first4=Leane |last5=McNulty |first5=Helene |title=Diet, nutrition and the ageing brain: current evidence and new directions |journal=Proceedings of the Nutrition Society |date=May 2018 |volume=77 |issue=2 |pages=152–163 |doi=10.1017/S0029665117004177|pmid=29316987 |s2cid=46282736|doi-access=free }}</ref>
* Limiting stress, adequate sleep, managing [[sensory impairment]]s, smoking cessation, limiting alcohol use, brain protection, treating [[Cardiovascular disease|cardiovascular]] risk factors<ref name="10.3233/JAD-201462"/>
* Avoiding [[anticholinergic]] medications<ref name="10.3233/JAD-201462"/>
* A number of {{tooltip|pharmacological strategies|dietary supplements and medications as well as their combination, dosages, scheduling, issues, etc}} are under investigation, including [[nicotinamide riboside]]<!--Note: Table 1--><ref name="10.1016/j.cmet.2018.05.011"/><ref>{{cite journal |last1=Braidy |first1=Nady |last2=Liu |first2=Yue |title=Can nicotinamide riboside protect against cognitive impairment? |journal=Current Opinion in Clinical Nutrition & Metabolic Care |date=November 2020 |volume=23 |issue=6 |pages=413–420 |doi=10.1097/MCO.0000000000000691 |pmid=32925178 |s2cid=221724061 |issn=1363-1950}}</ref>
* [[Calorie restriction|Caloric restriction]] and [[intermittent fasting]]<ref name="10.1016/j.cmet.2018.05.011">{{cite journal |last1=Mattson |first1=Mark P. |last2=Arumugam |first2=Thiruma V. |title=Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States |journal=Cell Metabolism |date=5 June 2018 |volume=27 |issue=6 |pages=1176–1199 |doi=10.1016/j.cmet.2018.05.011 |pmid=29874566 |pmc=6039826 |language=English |issn=1550-4131}}</ref>{{additional citation needed|date=March 2023}}
* The [[human microbiome|microbiome]] also plays a role. Scientists have shown that [[Fecal microbiota transplant|transplantation]] of [[Gut microbiota|fecal microbiota]] from young donor mice into aged recipient mice substantially [[rejuvenation|rejuvenates]] brain [[biomarker]]s of the latter,<ref>{{cite journal |last1=Boehme |first1=Marcus |last2=Guzzetta |first2=Katherine E. |last3=Bastiaanssen |first3=Thomaz F. S. |last4=van de Wouw |first4=Marcel |last5=Moloney |first5=Gerard M. |last6=Gual-Grau |first6=Andreu |last7=Spichak |first7=Simon |last8=Olavarría-Ramírez |first8=Loreto |last9=Fitzgerald |first9=Patrick |last10=Morillas |first10=Enrique |last11=Ritz |first11=Nathaniel L. |last12=Jaggar |first12=Minal |last13=Cowan |first13=Caitlin S. M. |last14=Crispie |first14=Fiona |last15=Donoso |first15=Francisco |last16=Halitzki |first16=Evelyn |last17=Neto |first17=Marta C. |last18=Sichetti |first18=Marzia |last19=Golubeva |first19=Anna V. |last20=Fitzgerald |first20=Rachel S. |last21=Claesson |first21=Marcus J. |last22=Cotter |first22=Paul D. |last23=O'Leary |first23=Olivia F. |last24=Dinan |first24=Timothy G. |last25=Cryan |first25=John F. |title=Microbiota from young mice counteracts selective age-associated behavioral deficits |journal=Nature Aging |date=August 2021 |volume=1 |issue=8 |pages=666–676 |doi=10.1038/s43587-021-00093-9 |pmid=37117767 |language=en |issn=2662-8465|doi-access=free}}
* News article about the study: {{cite news |title=Gut bacteria from young mice reverse signs of brain aging in old mice |url=https://newatlas.com/science/microbiome-brain-aging-gut-bacteria-neuroscience/ |access-date=21 September 2021 |work=New Atlas |date=10 August 2021}}</ref> complementing similar results of a 2020 study.<ref>{{cite journal |last1=Lee |first1=Juneyoung |last2=Venna |first2=Venugopal R. |last3=Durgan |first3=David J. |last4=Shi |first4=Huanan |last5=Hudobenko |first5=Jacob |last6=Putluri |first6=Nagireddy |last7=Petrosino |first7=Joseph |last8=McCullough |first8=Louise D. |last9=Bryan |first9=Robert M. |title=Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance |journal=Gut Microbes |date=9 November 2020 |volume=12 |issue=1 |article-number=1814107 |doi=10.1080/19490976.2020.1814107 |pmid=32897773 |issn=1949-0976|pmc=7757789}}</ref> Diet and other factors influence the microbiome. [[Probiotic]]s such as of ''[[Lactiplantibacillus plantarum|L. plantarum]]'' may also have relevant effects.<ref>{{cite journal |last1=Hutchinson |first1=Ashley N. |last2=Tingö |first2=Lina |last3=Brummer |first3=Robert Jan |title=The Potential Effects of Probiotics and ω-3 Fatty Acids on Chronic Low-Grade Inflammation |journal=Nutrients |date=August 2020 |volume=12 |issue=8 |page=2402 |doi=10.3390/nu12082402 |pmid=32796608 |pmc=7468753 |language=en |issn=2072-6643|doi-access=free}}</ref>

=== Cognitive reserve ===
{{Main|Cognitive reserve}}

The ability of an individual to demonstrate attenuated cognitive signs of aging despite an aging brain is called cognitive reserve.<ref name="Whalley 2004"/><ref name="Scarmeas 2003"/> This hypothesis suggests that two patients might have the same brain pathology, with one person experiencing noticeable clinical symptoms, while the other continues to function relatively normally. Studies of cognitive reserve explore the specific biological, genetic and environmental differences which make some people more resistant to cognitive decline than others. {{citation needed|date=November 2024}}

Intellectual quotients derived from psychometric testing have been identified as valuable proxy measures of cognitive reserve, with higher scores relative to the mean being associated with slower rates of cognitive decline.<ref>{{Cite journal |last1=Boyle |first1=R. |last2=Knight |first2=S. P. |last3=De Looze |first3=C. |last4=Carey |first4=D. |last5=Scarlett |first5=S. |last6=Stern |first6=Y. |last7=Robertson |first7=I. H. |last8=Kenny |first8=R. A. |last9=Whelan |first9=R. |date=2021-07-12 |title=Verbal intelligence is a more robust cross-sectional measure of cognitive reserve than level of education in healthy older adults |journal=Alzheimer's Research & Therapy |volume=13 |issue=1 |page=128 |doi=10.1186/s13195-021-00870-z |doi-access=free |issn=1758-9193 |pmc=8276413 |pmid=34253231}}</ref> However, the rate of decline in some cognitive subdomains, such as processing speed, may be less affected by premorbid IQ.<ref>{{Citation |last1=Gazes |first1=Yunglin |title=IQ moderation of cognitive decline supports cognitive reserve and not brain maintenance |date=2021-02-23 |url=https://www.medrxiv.org/content/10.1101/2021.02.19.21251920v1.full |access-date=2024-08-17 |language=en |doi=10.1101/2021.02.19.21251920 |last2=Lee |first2=Seonjoo |last3=Fang |first3=Zhiqian |last4=Mensing |first4=Ashley |last5=Noofoory |first5=Diala |last6=Nazario |first6=Geneva Hidalgo |last7=Babukutty |first7=Reshma |last8=Habeck |first8=Christian |last9=Stern |first9=Yaakov|doi-access=free }}</ref> The degree of association between IQ and cognitive reserve may vary between different types of dementia.<ref>{{Cite journal |last=Russ |first=Tom C. |date=2018-09-07 |title=Intelligence, Cognitive Reserve, and Dementia: Time for Intervention? |url=https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2701730#:~:text=If,%20as%20a%20result,%20cognitive,this%20is%20a%20vital%20question.&text=Corresponding%20Author:%20Tom%20C.,of%20Interest%20Disclosures:%20None%20reported. |journal=JAMA Network Open |volume=1 |issue=5 |article-number=e181724 |doi=10.1001/jamanetworkopen.2018.1724 |pmid=30646136 |issn=2574-3805|hdl=20.500.11820/49e0f5d6-4484-481d-ac8a-7530acf4b453 |hdl-access=free }}</ref>

===Research===
===="Super Agers"====

[[Longitudinal study|Longitudinal research studies]] have recently conducted [[Genetic analysis|genetic analyses]] of [[centenarian]]s and their offspring to identify protective factors against the negative effects of aging. In particular, the [[Cholesteryl ester transfer protein|CETP]] gene is linked to prevention of cognitive decline and Alzheimer's disease.<ref name="Sanders_2011">{{cite journal |last1=Sanders |first1=Amy |last2=Wang |first2=Cuiling |last3=Katz |first3=Mindy |last4=Derby |first4=Carol |last5=Barzilai |first5=Nir |year=2011 |title=Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia |journal=Journal of the American Medical Association |volume=303 |issue=2 |pages=150–158 |doi=10.1001/jama.2009.1988 |pmid=20068209 |pmc=3047443}}</ref> Specifically, [[valine]] CETP [[homozygote]]s but not [[heterozygote]]s experienced a relative 51% less decline in memory compared to a reference group after adjusting for demographic factors and [[Apolipoprotein E|APOE]] status.<ref name="Sanders_2011" />

====Nun Study====
{{Main|Nun Study}}
A study funded by the [[National Institute on Aging]] (NIA) began in 1986 and followed a group of 678 Roman Catholic sisters and recorded the effects of aging. The researchers used autobiographical essays collected as the nuns joined their Sisterhood. Findings suggest that early idea density, defined by number of ideas expressed and use of complex prepositions in these essays, was a significant predictor of lower risk for developing Alzheimer's disease in old age.  Lower idea density was found to be significantly associated with lower brain weight, higher [[cerebral atrophy]], and more [[neurofibrillary tangle]]s.<ref>{{cite journal |vauthors=Riley KP, Snowdon DA, Desrosiers MF, Markesbery WR | year = 2005 | title = Early life linguistic ability, late life cognitive function, and neuropathology: Findings from the Nun Study | journal = Neurobiology of Aging | volume = 26 | issue = 3| pages = 341–7 | doi=10.1016/j.neurobiolaging.2004.06.019| pmid = 15639312 | s2cid = 41770951}}</ref>

In 1994, [[Religious Orders Study]] has begun. Its initial funding was also provided by NIA.{{citation needed|date=November 2024}}

====Inflammation====
A study found that [[myeloid cell]]s are drivers of a [[Maladaptation|maladaptive]] [[Encephalitis|inflammation]] element of brain-[[ageing]] in mice and that this can be [[rejuvenation|reversed]] or prevented via inhibition of their EP2 signalling.<ref>{{cite news |title=Study reveals immune driver of brain aging |url=https://medicalxpress.com/news/2021-01-reveals-immune-driver-brain-aging.html |access-date=13 February 2021 |work=medicalxpress.com |language=en}}</ref><ref>{{cite journal |last1=Minhas |first1=Paras S. |last2=Latif-Hernandez |first2=Amira |last3=McReynolds |first3=Melanie R. |last4=Durairaj |first4=Aarooran S. |last5=Wang |first5=Qian |last6=Rubin |first6=Amanda |last7=Joshi |first7=Amit U. |last8=He |first8=Joy Q. |last9=Gauba |first9=Esha |last10=Liu |first10=Ling |last11=Wang |first11=Congcong |last12=Linde |first12=Miles |last13=Sugiura |first13=Yuki |last14=Moon |first14=Peter K. |last15=Majeti |first15=Ravi |last16=Suematsu |first16=Makoto |last17=Mochly-Rosen |first17=Daria |last18=Weissman |first18=Irving L. |last19=Longo |first19=Frank M. |last20=Rabinowitz |first20=Joshua D. |last21=Andreasson |first21=Katrin I. |title=Restoring metabolism of myeloid cells reverses cognitive decline in ageing |journal=Nature |date=February 2021 |volume=590 |issue=7844 |pages=122–128 |doi=10.1038/s41586-020-03160-0 |pmid=33473210 |language=en |issn=1476-4687|pmc=8274816 |bibcode=2021Natur.590..122M}}</ref>

====Cerebrospinal fluid====
[[File:Nervous system - Cerebrospinal fluid -- Smart-Servier.png|thumb|The cerebrospinal fluid circulates in the [[subarachnoid space]] around the brain and [[spinal cord]], and in the [[ventricular system|ventricles]] of the brain]]

A study showed that infusing the nourishing [[cerebrospinal fluid]] from around brain cells of young mice into aged brains rejuvenates aspects of the brain, proving that it play a role in brain aging and ''inter alia'' identifying a protein [[FGF17]] as a key target for potential therapeutics, including [[Life extension#EndogenousCirculatingBiomolecules|for anti-aging]].<ref>{{cite journal |last1=Iram |first1=Tal |last2=Kern |first2=Fabian |last3=Kaur |first3=Achint |last4=Myneni |first4=Saket |last5=Morningstar |first5=Allison R. |last6=Shin |first6=Heather |last7=Garcia |first7=Miguel A. |last8=Yerra |first8=Lakshmi |last9=Palovics |first9=Robert |last10=Yang |first10=Andrew C. |last11=Hahn |first11=Oliver |last12=Lu |first12=Nannan |last13=Shuken |first13=Steven R. |last14=Haney |first14=Michael S. |last15=Lehallier |first15=Benoit |last16=Iyer |first16=Manasi |last17=Luo |first17=Jian |last18=Zetterberg |first18=Henrik |last19=Keller |first19=Andreas |last20=Zuchero |first20=J. Bradley |last21=Wyss-Coray |first21=Tony |title=Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17 |journal=Nature |date=May 2022 |volume=605 |issue=7910 |pages=509–515 |doi=10.1038/s41586-022-04722-0 |pmid=35545674 |pmc=9377328 |bibcode=2022Natur.605..509I |s2cid=248741220 |language=en |issn=1476-4687}}
* News article about the study: {{cite news |last1=Yirka |first1=Bob |title=Giving an old mouse cerebrospinal fluid from a young mouse improves its memory |url=https://medicalxpress.com/news/2022-05-mouse-cerebrospinal-fluid-young-memory.html |access-date=22 June 2022 |work=medicalxpress.com |language=en}}
* Expert reviews of the study: {{cite web |title=Verjüngung der Gedächtnisleistung von alten Mäusen |url=https://www.sciencemediacenter.de/alle-angebote/research-in-context/details/news/verjuengung-der-gedaechtnisleistung-von-alten-maeusen/ |publisher=[[Science Media Centre#Other SMCs|Science Media Centre Germany]] |access-date=22 June 2022 |language=en}}</ref>

The [[subarachnoidal lymphatic-like membrane]], whose discovery was reported around 2023, likely plays a role in cerebrospinal fluid functions and, as both a protective barrier and a host of immune cells that monitor the brain for infection<!--[[List of infections of the central nervous system]]--> and [[Neuroinflammation|inflammation]], appears to be substantially involved in major brain diseases and brain aging. It is "the host for a large population of [[Myelocyte|myeloid cells]] [{{see above|[[#Inflammation|above]]}}], the number of which increases in response to inflammation and aging".<ref>{{cite journal |title=A mesothelium divides the subarachnoid space into functional compartments |journal=[[Science (journal)|Science]] |year=2023 |volume=379 |doi=10.1126/science.adc8810 |url=https://www.researchgate.net/publication/366903551 |last1=Møllgård |first1=Kjeld |last2=Beinlich |first2=Felix R. M. |last3=Kusk |first3=Peter |last4=Miyakoshi |first4=Leo M. |last5=Delle |first5=Christine |last6=Plá |first6=Virginia |last7=Hauglund |first7=Natalie L. |last8=Esmail |first8=Tina |last9=Rasmussen |first9=Martin K. |last10=Gomolka |first10=Ryszard S. |last11=Mori |first11=Yuki |last12=Nedergaard |first12=Maiken |issue=6627 |pages=84–88 |pmid=36603070 |bibcode=2023Sci...379...84M |s2cid=255440992}}
* University press release: {{cite news |title=Newly discovered anatomy shields and monitors brain |url=https://medicalxpress.com/news/2023-01-newly-anatomy-shields-brain.html |access-date=15 February 2023 |work=University of Rochester Medical Center via medicalxpress.com |language=en |archive-date=7 January 2023 |archive-url=https://web.archive.org/web/20230107034340/https://medicalxpress.com/news/2023-01-newly-anatomy-shields-brain.html |url-status=live}}
* News article about the study: {{cite news |last1=Charuchandra |first1=Sukanya |title=Scientists discover a new protective layer in the brain |url=https://www.advancedsciencenews.com/scientists-discover-a-new-protective-layer-in-the-brain/ |access-date=15 February 2023 |work=Advanced Science News |date=30 January 2023 |archive-date=30 January 2023 |archive-url=https://web.archive.org/web/20230130084439/https://www.advancedsciencenews.com/scientists-discover-a-new-protective-layer-in-the-brain/ |url-status=live}}</ref>

== Aging disparities ==
For certain demographics, the effects of normal cognitive aging are especially pronounced. Differences in cognitive aging might be tied to the lack of or reduced access to medical care and, as a result, suffer disproportionately from negative health outcomes. As the global population grows, diversifies, and grays, there is an increasing need to understand these inequities.{{citation needed|date=July 2022}}

=== Race ===

==== African Americans ====
[[File:Life expectancy in USA by race -only overall.png|thumb|Life expectancy in the US by race<ref name="NCHS_2021">{{cite journal|last1=Arias|first1=Elizabeth|last2=Xu|first2=Jiaquan|last3=Kochanek|first3=Kenneth|title=United States Life Tables, 2021|url=https://www.cdc.gov/nchs/data/nvsr/nvsr72/nvsr72-12.pdf|date=7 November 2023|journal=National Vital Statistics Reports|publisher=[[National Center for Health Statistics]]|volume=72|issue=12|pages=50–52}} — Table 19</ref>]]
[[File:Life expectancy in USA by race -sex gap.png|thumb|Life expectancy in the US by race and sex, with calculated sex gap<ref name="NCHS_2021" />]]
[[File:Percentage Surviving to Certain Ages in the US.png|thumb|Percentage surviving to certain ages in the US in 2019 by race and sex<ref name="NCHS_2019">{{cite journal|last1=Arias|first1=Elizabeth|last2=Xu|first2=Jiaquan|title=United States Life Tables, 2019|url=https://www.cdc.gov/nchs/data/nvsr/nvsr70/nvsr70-19.pdf|date=22 March 2022|journal=National Vital Statistics Reports|publisher=[[National Center for Health Statistics]]|volume=70|issue=19|pages=10–45 |pmid=35319436 }} — Tables 1–18</ref>]]

In the United States, Black and African American demographics disproportionately experience [[metabolic dysfunction]] with age. This has many downstream effects, but the most prominent of these is the toll on [[cardiovascular health]]. [[Metabolite]] profiles of the healthy aging index - a score that assesses neurocognitive function, among other correlates of health through the years - are associated with cardiovascular disease.<ref>{{Cite journal|last1=Yeri|first1=Ashish|last2=Murphy|first2=Rachel A|last3=Marron|first3=Megan M|last4=Clish|first4=Clary|last5=Harris|first5=Tamara B|last6=Lewis|first6=Gregory D|last7=Newman|first7=Anne B|last8=Murthy|first8=Venkatesh L|last9=Shah|first9=Ravi V|date=2017-12-14|title=Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study|journal=The Journals of Gerontology: Series A|volume=74|issue=1|pages=68–72|doi=10.1093/gerona/glx232|pmid=29253112|pmc=6298181|issn=1079-5006|doi-access=free}}</ref> Healthy cardiovascular function is critical for maintaining neurocognitive efficiency into old age. [[Attention]], verbal learning, and cognitive set ability are related to [[diastolic blood pressure]], [[triglyceride]] levels, and [[HDL cholesterol]] levels, respectively.<ref>{{Cite journal|last1=Sims|first1=Regina|last2=Madhere|first2=Serge|last3=Callender|first3=Clive|last4=Campbell|first4=Alfonso|date=2008|title=Patterns of relationships between cardiovascular disease risk factors and neurocognitive function in African Americans|journal=Ethnicity & Disease|volume=18|issue=4|pages=471–476|issn=1049-510X|pmc=3804014|pmid=19157252}}</ref>

==== Latinos ====
In the US, the Latino demographic is most likely to develop [[Epidemiology of metabolic syndrome|metabolic syndrome]] - the combination of [[Hypertension|high blood pressure]], high [[Blood sugar level|blood sugar]], [[Hypertriglyceridemia|elevated triglyceride levels]], and abdominal obesity - which not only increases the risk of [[cardiac event]]s and [[type 2 diabetes]] but also is associated with lower neurocognitive function during midlife.<ref>{{Cite journal|last1=González|first1=Hector M.|last2=Tarraf|first2=Wassim|last3=Vásquez|first3=Priscilla|last4=Sanderlin|first4=Ashley H.|last5=Rosenberg|first5=Natalya I.|last6=Davis|first6=Sonia|last7=Rodríguez|first7=Carlos J.|last8=Gallo|first8=Linda C.|last9=Thyagarajan|first9=Bharat|last10=Daviglus|first10=Martha|last11=Khambaty|first11=Tasneem|date=July 2018|title=Metabolic Syndrome and Neurocognition Among Diverse Middle-Aged and Older Hispanics/Latinos: HCHS/SOL Results|journal=Diabetes Care|volume=41|issue=7|pages=1501–1509|doi=10.2337/dc17-1896|issn=1935-5548|pmc=6014545|pmid=29716895}}</ref> This takes place even though [[life expectancy]] for Latinos in the US is higher than for white and black.<ref>{{cite web|last1=Arias |first1=Elizabeth |last2=Xu |first2=Jiaquan |url=https://www.cdc.gov/nchs/data/nvsr/nvsr71/nvsr71-01.pdf |title=National Vital Statistics Reports: United States Life Tables, 2020 |language=en |work=Centers for Disease Control and Prevention |date=8 August 2022}}</ref><ref>{{cite web|last1=Hill |first1=Latoya |last2=Artiga |first2=Samantha |url=https://www.kff.org/racial-equity-and-health-policy/issue-brief/what-is-driving-widening-racial-disparities-in-life-expectancy/ |title=What is Driving Widening Racial Disparities in Life Expectancy? |language=en |website=kff.org |date=23 May 2023}}</ref>

Among different Latin heritages, frequency of the dementia-predisposing ε4 allele of [[Apolipoprotein E#Alzheimer's disease|apoE4]] gene was highest for [[Antilles|Caribbean]] Latinos ([[Cubans]], [[People of the Dominican Republic|Dominicans]], [[Puerto Ricans]], 12.6–17.5 %) and lowest among mainland Latinos ([[Mexicans]], [[Central America]]ns, and [[South America]]ns, 11.0–11.2 %). At the same time, frequency of the neuroprotective ε2 allele was also highest for Caribbean Latinos (5.2–8.6 %) and lowest for those of mainland heritage (2.9–3.9 %). Among mainland Latinos, the most prevalent is the "median" ε3 allele: 85.2–86.2 % compared to 73.9–81.5% among Caribbean Latinos.<ref name="Gonzalez_2018">{{Cite journal|last1=González|first1=Hector M.|last2=Tarraf|first2=Wassim|last3=Jian|first3=Xueqiu|last4=Vásquez|first4=Priscilla M.|last5=Kaplan|first5=Robert|last6=Thyagarajan|first6=Bharat|last7=Daviglus|first7=Martha|last8=Lamar|first8=Melissa|last9=Gallo|first9=Linda C.|last10=Zeng|first10=Donglin|last11=Fornage|first11=Myriam|date=December 2018|title=Apolipoprotein E genotypes among diverse middle-aged and older Latinos: Study of Latinos-Investigation of Neurocognitive Aging results (HCHS/SOL)|journal=Scientific Reports|volume=8|issue=1|page=17578|doi=10.1038/s41598-018-35573-3|pmid=30546063|pmc=6292877|bibcode=2018NatSR...817578G|issn=2045-2322|doi-access=free}}</ref>

==== Indigenous Peoples ====
Indigenous populations are often understudied in research. Reviews of current literature studying natives in Australia, Brazil, Canada, and the United States from participants aged 45 to 94 years old reveal varied prevalence rates for cognitive impairment not related to dementia, from 4.4% to 17.7%.<ref>{{Cite journal|last1=de Souza-Talarico|first1=Juliana N.|last2=de Carvalho|first2=Anna P.|last3=Brucki|first3=Sonia M.D.|last4=Nitrini|first4=Ricardo|last5=Ferretti-Rebustini|first5=Renata E.de.L.|date=2016|title=Dementia and Cognitive Impairment Prevalence and Associated Factors in Indigenous Populations: A Systematic Review|journal=Alzheimer Disease & Associated Disorders|language=en|volume=30|issue=3|pages=281–287|doi=10.1097/WAD.0000000000000140|pmid=26840546|s2cid=24144093|issn=0893-0341}}</ref> These results can be interpreted in the context of culturally biased neurocognitive tests, preexisting health conditions, poor access to healthcare, lower [[educational attainment]], and/or old age.<ref>{{Cite journal|last1=Radford|first1=Kylie|last2=Lavrencic|first2=Louise M.|last3=Delbaere|first3=Kim|last4=Draper|first4=Brian|last5=Cumming|first5=Robert|last6=Daylight|first6=Gail|last7=Mack|first7=Holly A.|last8=Chalkley|first8=Simon|last9=Bennett|first9=Hayley|last10=Garvey|first10=Gail|last11=Hill|first11=Thi Yen|date=2019-08-13|editor-last=Anstey|editor-first=Kaarin|editor2-last=Peters|editor2-first=Ruth|title=Factors Associated with the High Prevalence of Dementia in Older Aboriginal Australians|journal=Journal of Alzheimer's Disease|volume=70|issue=s1|pages=S75–S85|doi=10.3233/JAD-180573|pmc=6700619|pmid=30507573}}</ref>

=== Sex ===

Compared to their male counterparts, women's scores on the [[mini–mental state examination]] (MMSE) tend to decline at slightly faster rates with age.<ref>{{Cite journal|last1=Lipnicki|first1=Darren M.|last2=Crawford|first2=John D.|last3=Dutta|first3=Rajib|last4=Thalamuthu|first4=Anbupalam|last5=Kochan|first5=Nicole A.|last6=Andrews|first6=Gavin|last7=Lima-Costa|first7=M. Fernanda|last8=Castro-Costa|first8=Erico|last9=Brayne|first9=Carol|last10=Matthews|first10=Fiona E.|last11=Stephan|first11=Blossom C. M.|date=2017-03-21|editor-last=Miller|editor-first=Bruce L.|title=Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study|journal=PLOS Medicine|language=en|volume=14|issue=3|article-number=e1002261|doi=10.1371/journal.pmed.1002261|issn=1549-1676|pmc=5360220|pmid=28323832 |doi-access=free }}</ref> Males with [[mild cognitive impairment]] tend to show more microstructural damage than females with MCI, but seem to have a greater [[cognitive reserve]] due to larger absolute brain size and neuronal density. As a result, women tend to manifest symptoms of cognitive decline at lower thresholds than men do.<ref>{{Cite journal|last1=O'Dwyer|first1=Laurence|last2=Lamberton|first2=Franck|last3=Bokde|first3=Arun L. W.|last4=Ewers|first4=Michael|last5=Faluyi|first5=Yetunde O.|last6=Tanner|first6=Colby|last7=Mazoyer|first7=Bernard|last8=O'Neill|first8=Desmond|last9=Bartley|first9=Máiréad|last10=Collins|first10=Rónán|last11=Coughlan|first11=Tara|date=2012-07-02|title=Sexual Dimorphism in Healthy Aging and Mild Cognitive Impairment: A DTI Study|journal=PLOS ONE|volume=7|issue=7|article-number=e37021|doi=10.1371/journal.pone.0037021|pmid=22768288|pmc=3388101|bibcode=2012PLoSO...737021O|issn=1932-6203|doi-access=free}}</ref> This effect seems to be moderated by [[educational attainment]] - higher education is associated with later diagnosis of mild cognitive impairment as neuropathological load increases.<ref>{{Cite journal|last1=Rapp|first1=Stephen R.|last2=Espeland|first2=Mark A.|last3=Manson|first3=Joann E.|last4=Resnick|first4=Susan M.|last5=Bryan|first5=Nick R.|last6=Smoller|first6=Sylvia|last7=Coker|first7=Laura H.|last8=Phillips|first8=Lawrence S.|last9=Stefanick|first9=Marcia L.|last10=Sarto|first10=Gloria E.|date=August 2013|title=Educational Attainment, MRI Changes, and Cognitive Function in Older Postmenopausal Women from the Women's Health Initiative Memory Study|url= |journal=The International Journal of Psychiatry in Medicine|volume=46|issue=2|pages=121–143|doi=10.2190/pm.46.2.a|pmid=24552037|issn=0091-2174|pmc=4544866}}</ref> Currently there are no known studies to identify a characteristic pattern of cognitive decline with age in [[Transgender|transgender people]].{{citation needed|date=November 2024}}

=== Socioeconomic factors ===
[[Socioeconomic status]] is the interaction between social and economic factors. It has been demonstrated that socio-demographic factors can be used to predict cognitive profiles within older individuals to some extent.<ref>{{Cite journal|last1=Santos|first1=Nadine Correia|last2=Moreira|first2=Pedro Silva|last3=Castanho|first3=Teresa Costa|last4=Sousa|first4=Nuno|last5=Costa|first5=Patrício Soares|date=2016-01-12|title=Discriminant power of socio-demographic characteristics and mood in distinguishing cognitive performance clusters in older individuals: a cross-sectional analysis|journal=Aging & Mental Health|volume=21|issue=5|pages=537–542|doi=10.1080/13607863.2015.1128879|pmid=26756965|issn=1360-7863|hdl=1822/46259|s2cid=25603962|hdl-access=free}}</ref>  This may be because families of higher socioeconomic status (SES) are equipped to provide their children with resources early on to facilitate cognitive development. For children in families of low SES, relatively small changes in parental income were associated with large changes in brain surface area; these losses were seen in areas associated with language, reading, [[executive functions]], and spatial skills. Meanwhile, for children in families of high SES, small changes in parental income were associated with small changes in surface area within these regions.<ref>{{Cite journal|last1=Piccolo|first1=Luciane R.|last2=Merz|first2=Emily C.|last3=He|first3=Xiaofu|last4=Sowell|first4=Elizabeth R.|last5=Noble|first5=Kimberly G.|date=2016-09-19|editor-last=Zuo|editor-first=Xi-Nian|title=Age-Related Differences in Cortical Thickness Vary by Socioeconomic Status|journal=PLOS ONE|language=en|volume=11|issue=9|article-number=e0162511|doi=10.1371/journal.pone.0162511|issn=1932-6203|pmc=5028041|pmid=27644039|bibcode=2016PLoSO..1162511P|doi-access=free}}</ref> With respect to global cortical thickness, low SES children showed a curvilinear decrease in thickness with age while those of high SES demonstrated a steeper linear decline, suggesting that [[synaptic pruning]] is more efficient in the latter group. This trend was especially evident in the left [[Fusiform gyrus|fusiform]] and left [[Superior temporal gyrus|superior temporal gyri]] - critical language and literacy supporting areas.<ref>{{Cite journal|last1=Noble|first1=Kimberly G|last2=Houston|first2=Suzanne M|last3=Brito|first3=Natalie H|last4=Bartsch|first4=Hauke|last5=Kan|first5=Eric|last6=Kuperman|first6=Joshua M|last7=Akshoomoff|first7=Natacha|last8=Amaral|first8=David G|last9=Bloss|first9=Cinnamon S|last10=Libiger|first10=Ondrej|last11=Schork|first11=Nicholas J|date=May 2015|title=Family income, parental education and brain structure in children and adolescents|url= |journal=Nature Neuroscience|language=en|volume=18|issue=5|pages=773–778|doi=10.1038/nn.3983|pmid=25821911|pmc=4414816|issn=1097-6256}}</ref>

A study showed that 50+ aged users of the dietary program [[Supplemental Nutrition Assistance Program|SNAP]] "had about 2 fewer years of cognitive aging over a 10-year period compared with non-users" despite it having nearly no conditions for the [[sustainable food system|sustainability]] and [[healthy diet|healthiness]] of the food products purchased with the [[coupon]]s (or coupon-credits).<ref>{{cite news |title=SNAP Use Linked to Slower Decline in Memory for Older Adults |url=https://www.neurologyadvisor.com/topics/general-neurology/snap-use-linked-to-slower-decline-in-memory-for-older-adults/ |access-date=17 December 2022 |work=Neurology Advisor |date=14 November 2022}}</ref><ref>{{cite journal |last1=Lu |first1=Peiyi |last2=Kezios |first2=Katrina |last3=Lee |first3=Jongseong |last4=Calonico |first4=Sebastian |last5=Wimer |first5=Christopher |last6=Hazzouri |first6=Adina Zeki Al |title=Association Between Supplemental Nutrition Assistance Program Use and Memory Decline: Findings From the Health and Retirement Study |journal=Neurology |date=9 November 2022 |volume=100 |issue=6 |article-number=e595–e602 |doi=10.1212/WNL.0000000000201499 |pmid=36351816 |pmc=9946186 |s2cid=253445156 |language=en |issn=0028-3878}}
* University press release: {{cite news |title=Using SNAP benefits may slow memory decline in older adults |url=https://medicalxpress.com/news/2022-11-snap-benefits-memory-decline-older.html |access-date=17 December 2022 |work=Columbia University's Mailman School of Public Health via medicalxpress.com |language=en}}</ref>

==See also==
{{div col|colwidth=30em}}
* [[Aging movement control]]
* [[Hallmarks of aging]]
* [[Life extension]]
* [[Lifelong learning]]
* [[Timeline of senescence research]]
* [[List of life extension related topics]]
* [[Neuropsychological test]]
* [[Reliability theory of aging and longevity]]
* [[Sensory stimulation therapy]]
* [[Neuroscience of aging]]
{{div col end}}

==References==
{{reflist|30em}}

==External links==
* National Institute on Aging: [https://web.archive.org/web/20130727130227/http://www.nia.nih.gov/research/cognitive-instrument Instruments to Detect Cognitive Impairment in Older Adults].

{{DEFAULTSORT:Aging Brain}}
[[Category:Central nervous system]]
[[Category:Senescence]]
[[Category:Brain]]