Restricted accessResearch articleFirst published online 2025
Telomere Length and Cognitive Function Among Middle-Aged and Older Participants From Communities Underrepresented in Aging Research: A Preliminary Study
Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.
Methods
This study included data on telomere length and neuropsychological test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.
Results
Nested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.
Discussion
Small sample size limited estimate precision; however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.
Adkins-JacksonP. B.GeorgeK. M.BesserL. M.HyunJ.LamarM.Hill-JarrettT. G.BubuO. M.FlattJ. D.HeynP. C.CiceroE. C.Zarina KraalA.Pushpalata ZanwarP.PetersonR.KimB.TurnerR. W.ViswanathanJ.KulickE. R.ZuelsdorffM.StitesS. D.…ManlyJ. J. (2023). The structural and social determinants of Alzheimer’s disease related dementias. Alzheimer's and Dementia: The Journal of the Alzheimer’s Association, 19(7), 3171–3185. https://doi.org/10.1002/alz.13027
2.
AlibertiM. J. R.CenzerI. S.SmithA. K.LeeS. J.YaffeK.CovinskyK. E. (2019). Assessing risk for adverse outcomes in older adults: The need to include both physical frailty and cognition. Journal of the American Geriatrics Society, 67(3), 477–483. https://doi.org/10.1111/jgs.15683
3.
AllisonS. L.JonaitisE. M.KoscikR. L.HermannB. P.MuellerK. D.CaryR. P.MaY.RowleyH. A.CarlssonC. M.AsthanaS.ZetterbergH.BlennowK.BendlinB. B.JohnsonS. C. (2021). Neurodegeneration, Alzheimer’s disease biomarkers, and longitudinal verbal learning and memory performance in late middle age. Neurobiology of Aging, 102, 151–160. https://doi.org/10.1016/j.neurobiolaging.2021.01.030
4.
Alzheimer’s Association. (2024). Alzheimer’s association 2024 Alzheimer’s disease facts and figures. Alzheimers Dement, 20(5), 3708–3821. https://doi.org/10.1002/alz.13809
5.
Avila-RiegerJ.TurneyI. C.VonkJ. M. J.EsieP.SeblovaD.WeirV. R.BelskyD. W.ManlyJ. J. (2022). Socioeconomic status, biological aging, and memory in a diverse national sample of older US men and women. Neurology, 99(19), e2114–e2124. https://doi.org/10.1212/WNL.0000000000201032
6.
BrownL.NeedhamB.AilshireJ. (2017). Telomere length among older U.S. Adults: Differences by race/ethnicity, gender, and age. Journal of Aging and Health, 29(8), 1350–1366. https://doi.org/10.1177/0898264316661390
ButtetM.BagheriR.UgbolueU. C.LaporteC.TrousselardM.BensonA.Bouillon-MinoisJ.-B.DutheilF. (2022). Effect of a lifestyle intervention on telomere length: A systematic review and meta-analysis. Mechanism of Ageing and Development, 206, Article 111694. https://doi.org/10.1016/j.mad.2022.111694
9.
ByunM. S.YiD.LeeJ. H.LeeJ.LeeH.KimY. K.LeeY.LeeD. Y. (2020). Telomere length, brain tau deposition and cognitive decline: Two-year follow-up study: Biomarkers (non-neuroimaging) / Novel biomarkers. Alzheimer's and Dementia, 16(S4), 045919. https://doi.org/10.1002/alz.045919
CaoZ.HouY.XuC. (2023). Leucocyte telomere length, brain volume and risk of dementia: A prospective cohort study. General Psychiatry, 36(4), Article e101120. https://doi.org/10.1136/gpsych-2023-101120
12.
CawthonR. M. (2009). Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Research, 37(3), e21. https://doi.org/10.1093/nar/gkn1027
13.
ChenC.YangK.NanH.UnverzagtF.McClureL. A.IrvinM. R.JuddS.CushmanM.Kamin MukazD.KlaunigJ. E.D’AltonM. E.KaheK. (2023). Associations of telomere length and change with cognitive decline were modified by sex and race: The REGARDS study. American Journal of Alzheimer's Disease and Other Dementias, 38, Article 15333175231175797. https://doi.org/10.1177/15333175231175797
14.
ClarkL. R.BermanS. E.NortonD.KoscikR. L.JonaitisE.BlennowK.BendlinB. B.AsthanaS.JohnsonS. C.ZetterbergH.CarlssonC. M. (2018). Age-accelerated cognitive decline in asymptomatic adults with CSF β-amyloid. Neurology, 90(15), e1306–e1315. https://doi.org/10.1212/WNL.0000000000005291
15.
CorriganJ. D.HinkeldeyN. S. (1987). Relationships between parts A and B of the Trail making test. Journal of Clinical Psychology, 43(4), 402–409. https://doi.org/10.1002/1097-4679(198707)43
16.
DavisonA.HinkleyD. (1997). Bootstrap methods and their application. Journal of the American Statistical Association, 94(445), 1271471. https://doi.org/10.2307/1271471
17.
De LoozeC.McCroryC.O’HalloranA.PolidoroS.Anne KennyR.FeeneyJ. (2024). Mind versus body: Perceived stress and biological stress are independently related to cognitive decline. Brain, Behavior, and Immunity, 115, 696–704. https://doi.org/10.1016/j.bbi.2023.10.017
18.
DruryS. S.MabileE.BrettZ. H.EstevesK.JonesE.ShirtcliffE. A.TheallK. P. (2014). The association of telomere length with family violence and disruption. Pediatrics, 134(1), e128–e137. https://doi.org/10.1542/peds.2013-3415
19.
EisenbergD.NettleD.VerhulstS. (2020). How to calculate the repeatability (ICC) of telomere length measures.
20.
ElamK. K.JohnsonS. L.RuofA.EisenbergD. T. A.RejP. H.SandlerI.WolchikS. (2022). Examining the influence of adversity, family contexts, and a family-based intervention on parent and child telomere length. European Journal of Psychotraumatology, 13(1), Article 2088935. https://doi.org/10.1080/20008198.2022.2088935
21.
ElliottM. L.CaspiA.HoutsR. M.AmblerA.BroadbentJ. M.HancoxR. J.HarringtonH.HoganS.KeenanR.KnodtA.LeungJ. H.MelzerT. R.PurdyS. C.RamrakhaS.Richmond-RakerdL. S.RighartsA.SugdenK.ThomsonW. M.ThorneP. R.…PoultonR. (2021). Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nature Aging, 1(3), 295–308. https://doi.org/10.1038/s43587-021-00044-4
22.
ForeroD. A.González-GiraldoY.López-QuinteroC.Castro-VegaL. J.BarretoG. E.PerryG. (2016). Meta-analysis of telomere length in Alzheimer’s disease. The journals of gerontology. Series A, Biological sciences and medical sciences, 71(8), 1069–1073. https://doi.org/10.1093/gerona/glw053
23.
GampawarP.SchmidtR.SchmidtH. (2020). Leukocyte telomere length is related to brain parenchymal fraction and attention/speed in the elderly: Results of the Austrian stroke prevention study. Frontiers in Psychiatry, 11(100), 100. https://doi.org/10.3389/fpsyt.2020.00100
24.
GeronimusA. T. (1992). The weathering hypothesis and the health of African-American women and infants: Evidence and speculations. Ethnicity & Disease, 2(3), 207–221.
25.
Gilmore-BykovskyiA. L.CroffR.GloverC. M.JacksonJ. D.ResendezJ.PerezA.ZuelsdorffM.Green-HarrisG.ManlyJ. J. (2022). Traversing the aging research and health equity divide: Toward intersectional frameworks of research justice and participation. The Gerontologist, 62(5), 711–720. https://doi.org/10.1093/geront/gnab107
26.
Gilmore-BykovskyiA. L.JinY.GleasonC.Flowers-BentonS.BlockL. M.Dilworth-AndersonP.BarnesL. L.ShahM. N.ZuelsdorffM. (2019). Recruitment and retention of underrepresented populations in Alzheimer’s disease research: A systematic review. Alzheimer’s and Dementia, 5, 751–770. https://doi.org/10.1016/j.trci.2019.09.018
27.
GleasonC. E.MartinW.StrongL.SummersM.LambrouN. H.ZuelsdorffM.ChinN. A.KrainerJ.LassilaP.MillerD. A.JacklinK.HendersonJ. N.WarryW.BlindM. J.SalazarH.SkenandoreD. W.EdwardsD. F.CarlssonC.AsthanaS. (2019). F4-06-02: Improving dementia outcomes in INDIAN country: The oneida nation ALZHEIMER’S disease project. Alzheimer's and Dementia, 15(7S_Part_23), P1227. https://doi.org/10.1016/j.jalz.2019.06.4734
28.
GlymourM. M.ManlyJ. J. (2008). Lifecourse social conditions and racial and ethnic patterns of cognitive aging. Neuropsychology Review, 18(3), 223–254. https://doi.org/10.1007/s11065-008-9064-z
29.
Green-HarrisG.ColeyS. L.KoscikR. L.NorrisN. C.HoustonS. L.SagerM. A.JohnsonS. C.EdwardsD. F. (2019). Addressing disparities in Alzheimer’s disease and african-American participation in research: An asset-based community development approach. Frontiers in Aging Neuroscience, 11(125), 125. https://doi.org/10.3389/fnagi.2019.00125
30.
GrodsteinF.OijenM. V.IrizarryM. C.RosasH. D.HymanB. T.GrowdonJ. H.VivoI. D. (2008). Shorter telomeres may mark early risk of dementia: Preliminary analysis of 62 participants from the nurses’ health study. PLoS One, 3(2), Article e1590. https://doi.org/10.1371/journal.pone.0001590
31.
HäggS.ZhanY.KarlssonR.GerritsenL.PlonerA.van der LeeS. J.BroerL.DeelenJ.MarioniR. E.WongA.LundquistA.ZhuG.HansellN. K.SillanpääE.FedkoI. O.AminN. A.BeekmanM.de CraenA. J. M.DegermanS.PedersenN. L.Martin-RuizC. M.MontgomeryG. W.AdolfssonA. N.ReynoldsC. A.SamaniN. J.SuchimanH. E. D.ViljanenA.von ZglinickiT.WrightM. J.HottengaJ. J.BoomsmaD. I.RantanenT.KaprioJ. A.NyholtD. R.MartinN. G.NybergL.AdolfssonR.KuhD.StarrJ. M.DearyI. J.SlagboomP. E.van DuijnC. M.CoddV.…NeuroCHARGE Cognitive Working Group (2017). Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. Translational Psychiatry, 7(4), e1100. https://doi.org/10.1038/tp.2017.73
32.
HansenM. E. B.HuntS. C.StoneR. C.HorvathK.HerbigU.RanciaroA.HirboJ.BeggsW.ReinerA. P.WilsonJ. G.KimuraM.De VivoI.ChenM. M.KarkJ. D.LevyD.NyamboT.TishkoffS. A.AvivA. (2016). Shorter telomere length in Europeans than in Africans due to polygenetic adaptation. Human Molecular Genetics, 25(11), 2324–2330. https://doi.org/10.1093/hmg/ddw070
33.
HochstrasserT.MarksteinerJ.HumpelC. (2012). Telomere length is age-dependent and reduced in monocytes of Alzheimer patients. Experimental Gerontology, 47(2), 160–163. https://doi.org/10.1016/j.exger.2011.11.012
34.
InselK. C.MerkleC. J.HsiaoC.-P.VidrineA. N.MontgomeryD. W. (2012). Biomarkers for cognitive aging Part I: Telomere length, blood pressure and cognition among individuals with hypertension. Biological Research For Nursing, 14(2), 124–132. https://doi.org/10.1177/1099800411406433
35.
JohnsonS. C.KoscikR. L.JonaitisE. M.ClarkL. R.MuellerK. D.BermanS. E.BendlinB. B.EngelmanC. D.OkonkwoO. C.HoganK. J.AsthanaS.CarlssonC. M.HermannB. P.SagerM. A. (2018). The Wisconsin Registry for Alzheimer’s prevention: A review of findings and current directions. Alzheimer’s and Dementia, 10, 130–142. https://doi.org/10.1016/j.dadm.2017.11.007
36.
JonaitisE. M.KoscikR. L.ClarkL. R.MaY.BetthauserT. J.BermanS. E.AllisonS. L.MuellerK. D.HermannB. P.Van HulleC. A.ChristianB. T.BendlinB. B.BlennowK.ZetterbergH.CarlssonC. M.AsthanaS.JohnsonS. C. (2019). Measuring longitudinal cognition: Individual tests versus composites. Alzheimer's and Dementia, 11(1), 74–84. https://doi.org/10.1016/j.dadm.2018.11.006
KimM.-J.KwonJ. S.ShinM.-S. (2013). Mediating effect of executive function on memory in normal aging adults. Psychiatry investigation, 108(2), 108–114. https://doi.org/10.4306/pi.2013.10.2.108
39.
KumeK.KikukawaM.HanyuH.TakataY.UmaharaT.SakuraiH.KanetakaH.OhyashikiK.OhyashikiJ. H.IwamotoT. (2012). Telomere length shortening in patients with dementia with Lewy bodies: Telomere shortening in DLB. European Journal of Neurology, 19(6), 905–910. https://doi.org/10.1111/j.1468-1331.2011.03655.x
40.
LeeM.WhitselE.AveryC.HughesT. M.GriswoldM. E.SedaghatS.GottesmanR. F.MosleyT. H.HeissG.LutseyP. L. (2022). Variation in population attributable fraction of dementia associated with potentially modifiable risk factors by race and ethnicity in the US. JAMA Network Open, 5(7), Article e2219672. https://doi.org/10.1001/jamanetworkopen.2022.19672
41.
LeibelD. K.ShakedD.MoodyB. D. L.LiuH. B.WengN.EvansM. K.ZondermanA. B.WaldsteinS. R. (2020). Telomere length and cognitive function: Differential patterns across sociodemographic groups. Neuropsychology, 34(2), 186–198. https://doi.org/10.1037/neu0000601
42.
LezakM. D. (2004). Neuropsychological assessment. Oxford University Press.
43.
LiuM.HuoY. R.WangJ.WangC.LiuS.LiuS.WangJ.JiY. (2016). Telomere shortening in Alzheimer’s disease patients. Annals of clinical and laboratory science, 46(3), 260–265.
44.
LivingstonG.HuntleyJ.LiuK. Y.CostafredaS. G.SelbækG.AlladiS.AmesD.BanerjeeS.BurnsA.BrayneC.FoxN. C.FerriC. P.GitlinL. N.HowardR.KalesH. C.KivimäkiM.LarsonE. B.NakasujjaN.RockwoodK.…SommerladA. (2024). Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet, 404(10452), 572–628. https://doi.org/10.1016/S0140-6736(24)01296-0
45.
LukensJ. N.Van DeerlinV.ClarkC. M.XieS. X.JohnsonF. B. (2009). Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimer’s disease. Alzheimer's and Dementia: The Journal of the Alzheimer's Association, 5(6), 463–469. https://doi.org/10.1016/j.jalz.2009.05.666
46.
MahoneyE. R.DumitrescuL.SetoM.NudelmanK. N. H.BuckleyR. F.GiffordK. A.SaykinA. J.JeffersonA. J.HohmanT. J. (2019). Telomere length associations with cognition depend on Alzheimer’s disease biomarkers. Alzheimer’s and Dementia, 5, 883–890. https://doi.org/10.1016/j.trci.2019.11.003
47.
MayedaE. R.GlymourM. M.QuesenberryC. P.WhitmerR. A. (2016). Inequalities in dementia incidence between six racial and ethnic groups over 14 years. Alzheimer's and Dementia: The Journal of the Alzheimer’s Association, 12(3), 216–224. https://doi.org/10.1016/j.jalz.2015.12.007
48.
Movérare-SkrticS.JohanssonP.MattssonN.HanssonO.WallinA.JohanssonJ.-O.ZetterbergH.BlennowK.SvenssonJ. (2012). Leukocyte telomere length (ltl) is reduced in stable mild cognitive impairment but low ltl is not associated with conversion to Alzheimer’s disease: A pilot study. Experimental Gerontology, 47(2), 179–182. https://doi.org/10.1016/j.exger.2011.12.005
49.
OlsonN. L.AlbensiB. C. (2020). Race- and sex-based disparities in Alzheimer’s disease clinical trial enrollment in the United States and Canada: An indigenous perspective. Journal of Alzheimer’s Disease Reports, 4(1), 325–344. https://doi.org/10.3233/ADR-200214
50.
PlassmanB. L.LangaK. M.McCammonR. J.FisherG. G.PotterG. G.BurkeJ. R.SteffensD. C.FosterN. L.GiordaniB.UnverzagtF. W.Welsh-BohmerK. A.HeeringaS. G.WeirD. R.WallaceR. B. (2011). Incidence of dementia and cognitive impairment, not dementia in the United States. Annals of Neurology, 70(3), 418–426. https://doi.org/10.1002/ana.22362
51.
PudasS.JosefssonM.Nordin AdolfssonA.LandforsM.KauppiK.Veng-TaastiL. M.HultdinM.AdolfssonR.DegermanS. (2021). Short leukocyte telomeres, but not telomere attrition rates, predict memory decline in the 20-year longitudinal betula study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 76(6), 955–963. https://doi.org/10.1093/gerona/glaa322
52.
Rodríguez-FernándezB.Sánchez BenavidesG.GeniusP.MinguillónC.FauriaK.De VivoI.Navarro CuartiellasA.MolinuevoJ. L.Gispert LópezJ. D.Sala VilaA.Vilor TejedorN.Crous-BouM.StudyA. (2024). Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer’s disease. Neurobiol Aging, 141, 140–150. https://doi.org/10.1016/j.neurobiolaging.2024.05.015
53.
R: The R Project for Statistical Computing. (nd). Retrieved September 12, 2024, from: https://www.r-project.org/
54.
ScarabinoD.BroggioE.GambinaG.CorboR. M. (2017). Leukocyte telomere length in mild cognitive impairment and Alzheimer’s disease patients. Experimental Gerontology, 98, 143–147. https://doi.org/10.1016/j.exger.2017.08.025
55.
ScarabinoD.PeconiM.BroggioE.GambinaG.MaggiE.ArmeliF.MantuanoE.MorelloM.CorboR. M.BusinaroR. (2020). Relationship between proinflammatory cytokines (Il-1beta, Il-18) and leukocyte telomere length in mild cognitive impairment and Alzheimer’s disease. Experimental Gerontology, 136, Article 110945. https://doi.org/10.1016/j.exger.2020.110945
StraussE.ShermanE. M. S.SpreenO. (2006). A compendium of neuropsychological tests: Administration, norms, and commentary. Oxford University Press.
58.
Suchy-DiceyA. M.MullerC. J.MadhyasthaT. M.ShibataD.ColeS. A.ZhaoJ.LongstrethW. T.BuchwaldD. (2018). Telomere length and magnetic resonance imaging findings of vascular brain injury and central brain atrophy: The strong Heart study. American Journal of Epidemiology, 187(6), 1231–1239. https://doi.org/10.1093/aje/kwx368
59.
ThomasP.CallaghanO. N. J.FenechM. (2008). Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer’s disease. Mechanism of Ageing and Development, 129(4), 183–190. https://doi.org/10.1016/j.mad.2007.12.004
VaisermanA.KrasnienkovD. (2020). Telomere length as a marker of biological age: State-of-the-Art, open issues, and future perspectives. Frontiers in Genetics, 11, Article 630186. https://doi.org/10.3389/fgene.2020.630186
62.
WeuveJ.BarnesL. L.Mendes De LeonC. F.RajanK. B.BeckT.AggarwalN. T.HebertL. E.BennettD. A.WilsonR. S.EvansD. A. (2018). Cognitive aging in Black and white Americans: Cognition, cognitive decline, and incidence of alzheimer disease dementia. Epidemiology, 29(1), 151–159. https://doi.org/10.1097/EDE.0000000000000747
63.
WuJ. W.YaqubA.MaY.KoudstaalW.HofmanA.IkramM. A.GhanbariM.GoudsmitJ. (2021). Biological age in healthy elderly predicts aging-related diseases including dementia. Scientific Reports, 11(1), Article 15929. https://doi.org/10.1038/s41598-021-95425-5
64.
ZhanY.ClementsM. S.RobertsR. O.VassilakiM.DrulinerB. R.BoardmanL. A.PetersenR. C.ReynoldsC. A.PedersenN. L.HäggS. (2018). Association of telomere length with general cognitive trajectories: A meta-analysis of four prospective cohort studies. Neurobiology of Aging, 69, 111–116. https://doi.org/10.1016/j.neurobiolaging.2018.05.004
65.
ZhuY.VorugantiV. S.LinJ.MatsuguchiT.BlackburnE.BestL. G.LeeE. T.MacCluerJ. W.ColeS. A.ZhaoJ. (2013). QTL mapping of leukocyte telomere length in American Indians: The Strong Heart Family Study. Aging, 5(9), 704–716. https://doi.org/10.18632/aging.100600
66.
ZuelsdorffM.OkonkwoO. C.NortonD.BarnesL. L.GrahamK. L.ClarkL. R.WymanM. F.BentonS. F.GeeA.LambrouN.JohnsonS. C.GleasonC. E. (2020). Stressful life events and racial disparities in cognition among middle-aged and older adults. Journal of Alzheimer's Disease: JAD, 73(2), 671–682. https://doi.org/10.3233/jad-190439
