Ethnic minorities seem to be at an increased risk of Alzheimer’s disease (AD). However, little is known about ethnic differences and the risks of early onset AD (EOAD).
Objective:
Cognitive function changes over time and odds of EOAD by ethnicity were analyzed by the mixed model and the logistic regression.
Methods:
Information on demographics, self-reported co-morbidities, cognitive functions (MMSE and ADAS-COG), and ApoE genotypes were collected for 6,500 subjects with AD obtained from the placebo arm of clinical trials; this data was examined by ethnicities: Caucasian, Asian, African American, Hispanic, and other minorities— including Native Alaskans, Americans, and Hawaiians.
Results:
Of the total subjects, Caucasians accounted for 89.0% , followed by 4.7% Asians, 2.7% African Americans, 2.4% Hispanics, and 1.2% Native Americans, Alaskans, and Hawaiians. Age, gender, EOAD status, co-morbidities, family history of AD, and ApoE genotypes were significantly different by ethnicity. ApoE ɛ2 allele is possibly overrepresented in the Native Americans, Africans, Hawaiians, and African Americans. A significant interaction with time, ethnicity, and cognitive performance was found, indicating more cognitive deterioration in other minorities than Caucasians for mini-mental state (p < 0.01). After adjusting for co-morbidities and gender, the odds of EOAD among African Americans (OR: 1.6, 95% CI: 1.1–2.4) and Native Alaskans, Americans, and Hispanics (OR: 2.1, 95% CI: 1.2–3.5) were significantly higher, compared with Caucasians.
Conclusions:
Ethnicity may impact AD through age of onset, co-morbidities, family history, ApoE gene status, and cognitive change over time. The greater odds of EOAD among African Americans, Alaskans, and Hawaiians suggest that some ethnicities may be at risk of AD at a younger age.
Alzheimer’s Association (2012) Alzheimer’s disease facts and figures. Alzheimers Dement8, 131–168.
2.
Alzheimer’s Association (2014) Alzheimer’s disease facts and figures. Alzheimers Dement10, e47–e92.
3.
HendrieHC (1998) Epidemiology of dementia and Alzheimer’s disease. Am J Geriatr Psychiatry6, S3–S18.
4.
FarrerLA, CupplesLA, HainesJL, HymanB, KukullWA, MayeuxR, MyersRH, Pericak-VanceMA, RischN, van DuijnCM (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. JAMA278, 1349–1356.
5.
JarmolowiczAI, ChenHY, PanegyresPK (2015) The patterns of inheritance in early-onset dementia: Alzheimer’s disease and frontotemporal dementia. Am J Alzheimers Dis Other Demen30, 299–306.
6.
FlemingerS, OliverDL, LovestoneS, Rabe-HeskethS, GioraA (2003) Head injury as a risk factor for Alzheimer’s disease: The evidence 10 years on; a partial replication. J Neurol Neurosurg Psychiatry74, 857–862.
7.
GreenRC, CupplesLA, KurzA, AuerbachS, GoR, SadovnickD, DuaraR, KukullWA, ChuiH, EdekiT, GriffithPA, FriedlandRP, BachmanD, FarrerL (2003) Depression as a risk factor for Alzheimer disease: The MIRAGE Study. Arch Neurol60, 753–759.
8.
ChangMH, MoonesingheR, AtharHM, TrumanBI (2016) Trends in disparity by sex and race/ethnicity for the leading causes of death in the United States: 1999-2010. J Public Health Manag Pract22 (Suppl 1), S13–S24.
9.
Chin AL, NegashS, HamiltonR (2011) Diversity and disparity in dementia: The impact of ethnoracial differences in Alzheimer’s disease. Alzheimer Dis Assoc Disord25, 187–195
10.
ManlyJJ, MayeuxR (2004) Ethnic differences in dementia and Alzheimer’s disease. Critical Perspectives on Racial and Ethnic Differentials in Health in Late Life, AndersonNE, BulataoRA, CohenB, eds. National Academies Press, Washington, DC.
11.
TangMX, SternY, MarderK, BellK, GurlandB, LantiguaR, AndrewsH, FengL, TyckoB, MayeuxR (1998) The ApoE (4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA279, 751–755.
12.
de Toledo Ferraz AlvesTC, FerreiraLK, WajangartenM, BusattoGF (2010) Cardiac disorders as risk factors for Alzheimer’s disease. J Alzheimers Dis20, 749–763.
13.
MortimerJA, GravesAB, AmyB (2000) Education and other socioeconomic determinants of dementia and Alzheimer’s disease. Neurology43, S39–S40.
14.
PanegyresPK, DavisS, ConnorC (2000) Early onset dementia. MJA173, 279–280.
15.
PanegyresPK, FrenchamK (2007) The course and causes of suspected dementia in young adults: A longitudinal study. Am J Alzheimers Dis Other Demen22, 48–56.
16.
MercyL, HodgesJR, DawsonK, BarkerRA, BrayneC (2008) Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology71, 1496–1499.
17.
Garre-OlmoJ, Genís BatlleD, del Mar FernándezM, Marquez DanielF, de Eugenio HuélamoR, CasadevallT, Turbau RecioJ, Turon EstradaA, López-PousaS, Registry of Dementia of Girona Study Group (ReDeGi Study Group) (2010) Incidence and subtypes of early-onset dementia in a geographically defined general population. Neurology75, 1249–1255.
18.
LambertMA1, BickelH, PrinceM, FratiglioniL, Von StraussE, FrydeckaD, KiejnaA, GeorgesJ, ReynishEL (2014) Estimating the burden of early onset dementia; systematic review of disease prevalence. Eur J Neurol21, 563–569.
19.
PanegyresPK, FrenchamK, DavisS (2003) The aetiology and natural history of cognitive decline in young adults: A five year cohort study of 201 patients. Aust J Psychology55S, 157.
AtkinsER, BulsaraMK, PanegyresPK (2012) The natural history of early-onset dementia: The Artemis Project. BMJ Open2(5), e001764.
22.
PanegyresPK, ChenH-Y (2013) Differences between early and late onset Alzheimer’s disease. Am J Neurodegener Dis2, 300–306.
23.
FairjonesSE, VuletichEJ, PestellC, PanegyresPK (2011) Exploring the role of cognitive reserve in early-onset dementia. Am J Alzheimers Dis Other Demen26, 39–44.
24.
FrisoniGB1, PievaniM, TestaC, SabattoliF, BrescianiL, BonettiM, BeltramelloA, HayashiKM, TogaAW, ThompsonPM (2007) The topography of grey matter involvement in early and late onset Alzheimer’s disease. Brain130, 720–730.
25.
SáF, PintoP, CunhaC, LemosR, LetraL, SimõesM, SantanaI (2012) Differences between early and late-onset Alzheimer’s disease in neuropsychological tests. Front Neurol3, 81.
26.
SmitsLL, PijnenburgYA, KoedamEL (2012) Early onset Alzheimer’s disease is associated with a distinct neuropsychological profile. J Alzheimers Dis30, 101–108.
27.
McKhannGM, DrachmanD, FolsteinM (1984) Clinical Diagnosis of Alzheimer’s Disease: Report of the NINCDS-ADRA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology34, 939–944.
28.
ShadlenM-F, McCormickWC, LarsonEB (2012) Research agenda for understanding Alzheimer disease in diverse populations: Work group on cultural diversity, Alzheimer’s association. Alzheimer Dis Assoc Disord16, S96–S100.
29.
Critical Path Institute. Critical Path Online Data Repository (CODR): Coalition Against Major Disease (CAMD) Alzheimer’s Disease, http://c-path.org/programs/camd/camd-codr/, Accessed 22 February 2015.
30.
DutheyB (2013) Update on 2004 Background Paper 6.11: Alzheimer disease and other dementias. In Priority Medicines for Europe and the World, KaplanW, WirtzVJ, Mantel TeeuwisseA, StolkP, DutheyB, LaingR, (eds). World Health Organisaiton, Switzerland, pp
1–74.
31.
SternY, FolsteinM, AlbertM, RichardsM, MillerL, BylsmaF, LaflecheG, MarderK, BellK, SanoM (1993) Multicenter study of predictors of disease course in Alzheimer disease (the “Predictors Study”). I. Study design, cohort description, and intersite comparisons. Alzheimer Dis Assoc Disord7, 3–21.
32.
LuchsingerJ, TangM-X, SternY, SheaS, MayeuxR (2001) Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol154, 635–641.
33.
LuchsingerJ, ReitzC, HonigLS, TangMX, SheaS, MayeuxR (2005) Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology65, 545–551.
34.
GorelickPB, FreelsS, HarrisY, DollearT, BillingsleyM, BrownN (1994) Epidemiology of vascular and Alzheimer’s dementia among African Americans in Chicago, IL: Baseline frequency and comparison of risk factors. Neurology44, 1391.
35.
ShadlenMF, LarsonEB, YukawaM (2000) The epidemiology of Alzheimer’s disease and vascular dementia in Japanese and African-American populations: The search for etiological clues. Neurobiol Aging21, 171–181.
36.
RomanoJG, ArauzA, KochS, DongC, MarquezJM, ArtigasC, MerlosM, HernandezB, RoaLF, RundekT, SaccoRL (2013) Disparities in stroke type and vascular risk factors between 2 Hispanic populations in Miami and Mexico city. J Stroke Cerebrovasc Dis22, 828–833.
37.
van DuijnCM, de KnijffP, WehnertA, De VoechtJ, BronzovaJB, HavekesLM, HofmanA, Van BroeckhovenC (1995) The apolipoprotein E epsilon 2 allele is associated with an increased risk of early-onset Alzheimer’s disease and a reduced survival. Ann Neurol37, 605–610.
38.
CorderEH, SaundersAM, RischNJ, StrittmatterWJ, SchmechelDE, GaskellPCJr, RimmlerJB, LockePA, ConneallyPM, SchmaderKE (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet7, 180–184.
39.
PanzaF, SolfrizziV, TorresF, MastroianniF, ColaciccoAM, BasileAM, CapursoC, D’IntronoA, Del ParigiA, CapursoA (2000) Apolipoprotein E in Southern Italy: Protective effect of epsilon 2 allele in early- and late-onset sporadic Alzheimer’s disease. Neurosci Lett292, 79–82.
40.
ScarmeasN, AlbertS, ManlyJJ, SteryY (2006) Education and rates of cognitive decline in incident Alzheimer’s disease. J Neurol Neurosurg Psychiatry77, 308–316.
41.
WilsonRS, LiY, AggarwalNT, BarnesLL, McCannJJ, GilleyDW, EvansDA (2004) Education and the course of cognitive decline in Alzheimer disease. Neurology63, 1198–1202.
42.
WitteMM, TrzepaczP, CaseM, YuP, HochstetlerH, QuinlivanM, SundellK, HenleyD (2014) Association between clinical measures and Florbetapir F18 PET neuroimaging in mild or moderate Alzheimer’s disease dementia. J Neuropsychol Clin Neurosci26, 214–220.
43.
MonsellSE, KukullWA, RoherAE, MaaroufCL, SerranoG, BeachTG, CaselliRJ, MontineTJ, ReimanEM (2015) Characterizing apolipoprotein E e4 carriers and noncarriers with the clinical diagnosis of mild to moderate Alzheimer dementia and minimal (-amyloid peptide plaques. JAMA Neurol72, 1124–1131.
44.
KarpA, KåreholtI, QuiC, BellanderT, WinbladB, FratiglioniL (2004) Relation of education and occupation-based socioeconomic status to incident Alzheimer’s disease. Am J Epidemiol159, 175–183.
45.
EscobarJI, BurnamA, KarnoM, ForsytheA, LandsverkJ, GoldingJM (1986) Use of the Mini-Mental State Examination (MMSE) in a community population of mixed ethnicity: Cultural and linguistic artifacts. J Nerv Ment Dis174, 607–614.
