Restricted accessResearch articleFirst published online 2025-12
Sociodemographic correlates of cognition and Alzheimer's disease and vascular biomarkers among middle to older age participants in the Healthy Brain Initiative
Key sociodemographics (e.g., nativity) plausibly related to Alzheimer's disease and related dementia (ADRD) risk have been investigated less frequently in relation to cognitive function, brain imaging, and blood-based biomarkers.
Objective
To examine associations between multiple sociodemographics and ADRD/vascular outcomes among middle- to older-age adults.
Methods
We used cross-sectional data on 341 Healthy Brain Initiative participants. Outcomes included cognitive domain scores (e.g., episodic memory, language), magnetic resonance imaging (MRI) (e.g., hippocampal and white matter hyperintensity volume), and blood-based biomarkers (e.g., Aβ42/40, pTau-217, NfL, GFAP). Sociodemographics included age, sex, racial group, Hispanic ethnicity, primary language, nativity, socioeconomic position, area deprivation, and living alone. Multivariable linear regression examined associations between sociodemographics and brain health outcomes.
Results
Mean age was 69 ± 9 and 71% were women. Older individuals, women, Black and Hispanic individuals, those of lower socioeconomic position, and those born outside the US performed worse across various cognitive domains, while those who primarily spoke Spanish (versus English) scored better on episodic memory. Older individuals, women, and Hispanic individuals had worse brain health, and those identifying as other racial group and born outside of the US had better brain health measured via MRI. Older and Hispanic individuals had worse brain health and Black individuals and women had better brain health as measured via blood-based biomarkers.
Conclusions
This study contributes to the growing number of studies identifying differences in ADRD/vascular biomarkers by sociodemographics. Additional studies are needed to assess whether social and economic determinants of health are associated with longitudinal change in ADRD/vascular biomarkers.
MontineTJPhelpsCHBeachTG, et al.National institute on aging-Alzheimer's association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol2012; 123: 1–11.
3.
SperlingRAAisenPSBeckettLA, et al.Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011; 7: 280–292.
4.
FrigerioRFujishiroHAhnTB, et al.Incidental Lewy body disease: do some cases represent a preclinical stage of dementia with Lewy bodies?Neurobiol Aging2011; 32: 857–863.
5.
BenussiAAlbericiASamraK, et al.Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia. Alzheimers Dement2022; 18: 1408–1423.
6.
GorelickPBScuteriABlackSE, et al.Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American stroke association. Stroke2011; 42: 2672–2713.
7.
McKhannGMKnopmanDSChertkowH, et al.The diagnosis of dementia due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011; 7: 263–269.
8.
AfrinMRUpadhyayaPGHashimA, et al.Advanced biomarkers: beyond amyloid and tau: emerging non-traditional biomarkers for Alzheimer;s diagnosis and progression. Ageing Res Rev2025; 108: 102736.
9.
WeintraubSBesserLDodgeHH, et al.Version 3 of the Alzheimer disease Centers’ neuropsychological test battery in the uniform data set (UDS). Alzheimer Dis Assoc Disord2018; 32: 10–17.
10.
OnyikeCUDiehl-SchmidJ. The epidemiology of frontotemporal dementia. Int Rev Psychiatry2013; 25: 130–137.
11.
McKeithIGDicksonDWLoweJ, et al.Diagnosis and management of dementia with Lewy bodies: third report of the DLB consortium. Neurology2005; 65: 1863–1872.
12.
GibbonsCHLevineTAdlerC, et al.Skin biopsy detection of phosphorylated alpha-synuclein in patients with synucleinopathies. JAMA2024; 331: 1298–1306.
13.
O'SheaDMArkhipenkoAGalaskoD, et al.Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions. Front Neurol2024; 15: 1395413.
14.
FosterNLHeidebrinkJLClarkCM, et al.FDG-PET improves accuracy in distinguishing frontotemporal dementia and Alzheimer's disease. Brain2007; 130: 2616–2635.
15.
FitzpatrickALRappSRLuchsingerJ, et al.Sociodemographic correlates of cognition in the multi-ethnic study of atherosclerosis (MESA). Am J Geriatr Psychiatry2015; 23: 684–697.
16.
KovalevaMJonesAMaxwellCA. Immigrants and dementia: literature update. Geriatr Nurs2021; 42: 1218–1221.
17.
Adkins-JacksonPBGeorgeKMBesserLM, et al.The structural and social determinants of Alzheimer's disease related dementias. Alzheimers Dement2023; 19: 3171–3185.
18.
MorrisJCSchindlerSEMcCueLM, et al.Assessment of racial disparities in biomarkers for Alzheimer disease. JAMA Neurol2019; 76: 264–273.
19.
MorrisonCDadarMManeraAL, et al.Racial differences in white matter hyperintensity burden in older adults. Neurobiol Aging2023; 122: 112–119.
20.
KjaergaardDSimonsenAHWaldemarG, et al.Ethnic and racial influences on blood biomarkers for Alzheimer's disease: a systematic review. J Alzheimers Dis2025; 103: 81–91.
21.
BrickmanAMSchupfNManlyJJ, et al.Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan. Arch Neurol2008; 65: 1053–1061.
22.
BesserLMFuentesAJZhangJN, et al.Intersectionality of gender with social determinants of health and asymptomatic Alzheimer's disease neuropathology. J Alzheimers Dis2024; 102: 110–118.
23.
BesserLMChrisphonteSKleimanMJ, et al.The healthy brain initiative (HBI): a prospective cohort study protocol. PLoS One2023; 18: e0293634.
24.
HollingsheadAB. Two factor index of social position. New Haven, CT: B. Hollingshead, 1957.
HuntJFVBuckinghamWKimAJ, et al.Association of neighborhood-level disadvantage with cerebral and hippocampal volume. JAMA Neurol2020; 77: 451–460.
27.
HuntJFVVogtNMJonaitisEM, et al.Association of neighborhood context, cognitive decline, and cortical change in an unimpaired cohort. Neurology2021; 96: e2500–e2512.
28.
GogniatMAKhanOARatangeeB, et al.Cross-sectional and longitudinal associations of neighborhood disadvantage with fluid biomarkers of neuroinflammation and neurodegeneration. Neurology2025; 105: e213770.
29.
BesserLKukullWKnopmanDS, et al.Version 3 of the national Alzheimer's coordinating center's uniform data set. Alzheimer Dis Assoc Disord2018; 32: 351–358.
30.
CraftSNewcomerJKanneS, et al.Memory improvement following induced hyperinsulinemia in Alzheimer's disease. Neurobiol Aging1996; 17: 123–130.
31.
ShapiroAMBenedictRHSchretlenD, et al.Construct and concurrent validity of the Hopkins verbal learning test-revised. Clin Neuropsychol1999; 13: 348–358.
32.
GalvinJEToleaMIMooreC, et al.The number symbol coding task: a brief measure of executive function to detect dementia and cognitive impairment. PLoS One2020; 15: e0242233.
33.
TombaughTN. Trail making test A and B: normative data stratified by age and education. Arch Clin Neuropsychol2004; 19: 203–214.
34.
GriffinPTHeffernanA. Digit span, forward and backward - separate and unequal components of the wais digit span. Percept Mot Skills1983; 56: 335–338.
35.
JiskootLCRussellLLPeakmanG, et al.The Benson Complex figure test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: a GENFI study. J Neurol Sci2023; 446: 120590.
36.
KoikkalainenJRRhodius-MeesterHFMFrederiksenKS, et al.Automatically computed rating scales from MRI for patients with cognitive disorders. Eur Radiol2019; 29: 4937–4947.
WardlawJMValdes HernandezMCMunoz-ManiegaS. What are white matter hyperintensities made of? Relevance to vascular cognitive impairment. J Am Heart Assoc2015; 4: 001140.
KandelBMAvantsBBGeeJC, et al.White matter hyperintensities are more highly associated with preclinical Alzheimer's disease than imaging and cognitive markers of neurodegeneration. Alzheimers Dement (Amst)2016; 4: 18–27.
41.
DebetteSHSM. The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis. Br Med J2010; 341: c3666.
42.
ApostolovaLGGreenAEBabakchanianS, et al.Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and Alzheimer disease. Alzheimer Dis Assoc Disord2012; 26: 17–27.
43.
KaipainenALPitkanenJHaapalinnaF, et al.A novel CT-based automated analysis method provides comparable results with MRI in measuring brain atrophy and white matter lesions. Neuroradiology2021; 63: 2035–2046.
44.
GrandeGVallettaMRizzutoD, et al.Blood-based biomarkers of Alzheimer's disease and incident dementia in the community. Nat Med2025; 31: 2027–2035.
45.
MeyerMRKirmessKMEastwoodS, et al.Clinical validation of the PrecivityAD2 blood test: a mass spectrometry-based test with algorithm combining %p-tau217 and Abeta42/40 ratio to identify presence of brain amyloid. Alzheimers Dement2024; 20: 3179–3192.
46.
RissinDMKanCWCampbellTG, et al.Single-molecule enzyme-linked immunosorbent assay detects serum proteins at subfemtomolar concentrations. Nat Biotechnol2010; 28: 595–599.
CharlsonMEPompeiPAlesKL, et al.A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis1987; 40: 373–383.
50.
GrollDLToTBombardierC, et al.The development of a comorbidity index with physical function as the outcome. J Clin Epidemiol2005; 58: 595–602.
51.
MorrisJC. The clinical dementia rating (CDR): current version and scoring rules. Neurology1993; 43: 2412–2414.
52.
Jack JrCRWisteHJAlgeciras-SchimnichA, et al.Comparison of plasma biomarkers and amyloid PET for predicting memory decline in cognitively unimpaired individuals. Alzheimers Dement2024; 20: 2143–2154.
53.
BenjaminiYHochbergY. Controlling the false discovery rate - a practical and powerful approach to multiple testing. J R Stat Soc B1995; 57: 289–300.
54.
StreinerDL. Best (but oft-forgotten) practices: the multiple problems of multiplicity-whether and how to correct for many statistical tests. Am J Clin Nutr2015; 102: 721–728.
55.
RothmanKJ. No adjustments are needed for multiple comparisons. Epidemiology1990; 1: 43–46.
56.
RicardJAParkerTCDhamalaE, et al. Confronting racially exclusionary practices in the acquisition and analyses of neuroimaging data. Nat Neurosci2023; 26: 4–11.
57.
BesserLMMitsovaDWilliamsCL, et al. Redlining and neighborhood walking in older adults: The 2017 National Household Travel Survey. Am J Prev Med2022; 63: 926–934.
58.
WilliamsDRCollinsC. Racial residential segregation: a fundamental cause of racial disparities in health. Public Health Rep2001; 116: 404–416.
59.
HajjarIYangZOkaforM, et al.Association of plasma and cerebrospinal fluid Alzheimer disease biomarkers with race and the role of genetic ancestry, vascular comorbidities, and neighborhood factors. JAMA Netw Open2022; 5: e2235068.
60.
WangWEAskenBMDeSimoneJC, et al.Neuroimaging and biofluid biomarkers across race and ethnicity in older adults across the spectrum of cognition. Ageing Res Rev2024; 101: 102507.
61.
FarkhondehVDeCarliC. White matter hyperintensities in diverse populations: a systematic review of literature in the United States. Cereb Circ Cogn Behav2024; 6: 100204.
62.
HillTDAngelJLBalistreriKS, et al.Immigrant status and cognitive functioning in late-life: an examination of gender variations in the healthy immigrant effect. Soc Sci Med2012; 75: 2076–2084.
63.
MarkidesKSRoteS. The healthy immigrant effect and aging in the United States and other western countries. Gerontologist2019; 59: 205–214.
64.
VenugopalAPaplikarAVargheseFA, et al.Protective effect of bilingualism on aging, MCI, and dementia: a community-based study. Alzheimers Dement2024; 20: 2620–2631.
65.
EstangaAEcay-TorresMIbanezA, et al.Beneficial effect of bilingualism on Alzheimer's disease CSF biomarkers and cognition. Neurobiol Aging2017; 50: 144–151.
66.
BesserLMEdwardsKLobbanNS, et al.Social determinants of health, risk and resilience against Alzheimer's disease and related dementias: the healthy brain initiative. J Alzheimers Dis Rep2024; 8: 637–646.
67.
SolKMorrisEPLeeJH, et al.Histories of neighborhood socioeconomic status contribute to race differences in later-life cognition. Alzheimers Dement2024; 20: 3342–3351.
68.
LivingstonGHuntleyJLiuKY, et al.Dementia prevention, intervention, and care: 2024 report of the lancet standing commission. Lancet2024; 404: 572–628.
69.
Office of the Surgeon General (OSG). Our Epidemic of Loneliness and Isolation: The U.S. Surgeon General’s Advisory on the Healing Effects of Social Connection and Community. Washington, DC: US Department of Health and Human Services, 2023.
70.
TerraccianoAWalkerKAAnY, et al.Loneliness and biomarkers of Alzheimer's disease, axonal damage, and astrogliosis: a coordinated analysis of two longitudinal cohorts. J Gerontol B Psychol Sci Soc Sci2025; 80: gbaf006.
71.
GuarneraJYuenEMacphersonH. The impact of loneliness and social isolation on cognitive aging: a narrative review. J Alzheimers Dis Rep2023; 7: 699–714.
WhiteIRCarlinJB. Bias and efficiency of multiple imputation compared with complete-case analysis for missing covariate values. Stat Med2010; 29: 2920–2931.
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