The aim of the study is to ascertain the neuropsychiatric symptoms (NPS) subtypes significantly influencing progression to mild cognitive impairment (MCI) by ethnicity. In this retrospective cohort study, we included 386 cognitively normal individuals participating in the longitudinal Texas Alzheimer’s Research and Care Consortium between February 2007 and August 2014. The primary outcome was time to incident MCI. Data driven NPS subtypes at baseline were identified and the effects of these subtypes on the outcome were obtained for Hispanic and non-Hispanic ethnic cohorts and summarized with a hazard ratio (HR). Three NPS subtypes were identified and internally validated: psychomotor apathy factor (including agitation, irritability, apathy), affective mood factor (including depression, anxiety), and physical behavior factor (including nighttime behavior, eating/appetite disturbances). In adjusted analysis, a psychomotor apathy score of NPS was the best predictor for MCI (HR = 2.19, p = 0.037) among non-Hispanics whereas physical behavior score was the most predictive of MCI (HR = 2.55, p = 0.029) among Hispanics. A high score of affective mood factor also tended to increase the risk of MCI (HR = 2.09, p = 0.06) in Hispanics. Progression from normal cognition to MCI was differentially predicted by NPS subtypes in Hispanics and non-Hispanic whites. These data may inform the allocation of efforts for monitoring individuals at-risk of MCI.
AbnerELKryscioRJSchmittFA, et al.Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol. 2017;81(4):549–559.
2.
ModregoPJFerrandezJ. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study. Arch Neurol. 2004;61(8):1290–1293.
3.
RosenbergPBMielkeMMApplebyBSOhESGedaYELyketsosCG. The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. Am J Geriatr Psychiatry. 2013;21(7):685–695.
4.
CerejeiraJLagartoLMukaetova-LadinskaEB. Behavioral and psychological symptoms of dementia. Front Neurol. 2012;3:73.
5.
ForresterSNGalloJJSmithGSLeoutsakosJM. Patterns of neuropsychiatric symptoms in mild cognitive impairment and risk of dementia. Am J Geriatr Psychiatry. 2016;24(2):117–125.
6.
ApostolovaLGCummingsJL. Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature. Dement Geriatr Cogn Disord. 2008;25(2):115–126.
7.
DinizBSButtersMAAlbertSMDewMAReynoldsCF. Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329–335.
8.
HwangTJMastermanDLOrtizFFairbanksLACummingsJL. Mild cognitive impairment is associated with characteristic neuropsychiatric symptoms. Alzheimer Dis Assoc Disord. 2004;18(1):17–21.
9.
IsmailZAguera-OrtizLBrodatyH, et al.The Mild Behavioral Impairment Checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. J Alzheimers Dis. 2017;56(3):929–938.
10.
GedaYERobertsROKnopmanDS, et al.Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Arch Gen Psychiatry. 2008;65(10):1193–1198.
11.
SalazarRDwivediAKRoyallDR. Cross-ethnic differences in the severity of neuropsychiatric symptoms in persons with mild cognitive impairment and Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2017;29(1):13–21.
12.
BanksSJRamanRHeF, et al.The Alzheimer’s disease cooperative study prevention instrument project: longitudinal outcome of behavioral measures as predictors of cognitive decline. Dement Geriatr Cogn Dis Extra. 2014;4(3):509–516.
13.
CummingsJLMegaMGrayKRosenberg-ThompsonSCarusiDAGornbeinJ. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology. 1994;44(12):2308–2314.
14.
CummingsJL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(5 suppl 6): S10–16.
15.
KauferDICummingsJLKetchelP, et al.Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci. 2000;12(2):233–239.
16.
BurhanullahMHTschanzJTPetersME, et al.Neuropsychiatric symptoms as risk factors for cognitive decline in clinically normal older adults: the Cache County Study. Am J Geriatr Psychiatry. 2020;28(1):64–71.
17.
GedaYERobertsROMielkeMM, et al.Baseline neuropsychiatric symptoms and the risk of incident mild cognitive impairment: a population-based study. Am J Psychiatry. 2014;171(5):572–581.
18.
PankratzVSRobertsROMielkeMM, et al.Predicting the risk of mild cognitive impairment in the Mayo Clinic Study of Aging. Neurology. 2015;84(14):1433–1442.
19.
MastersMCMorrisJCRoeCM. “Noncognitive” symptoms of early Alzheimer disease: a longitudinal analysis. Neurology. 2015;84(6):617–622.
20.
BabulalGMStoutSHHeadD, et al.Neuropsychiatric symptoms and Alzheimer’s disease biomarkers predict driving decline: brief report. J Alzheimers Dis. 2017;58(3):675–680.
21.
TangMXCrossPAndrewsH, et al.Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology. 2001;56(1):49–56.
22.
MehtaKMYeoGW. Systematic review of dementia prevalence and incidence in United States race/ethnic populations. Alzheimers Dement. 2017;13(1):72–83.
23.
O’BryantSEHumphreysJDSchifferRBSutkerPB. Presentation of Mexican Americans to a memory disorder clinic. J Psychopathol Behav Assess. 2007;29(3):137.
24.
ClarkCMDeCarliCMungasD, et al.Earlier onset of Alzheimer disease symptoms in Latino individuals compared with Anglo individuals. Arch Neurol. 2005;62(5):774–778.
25.
FittenLJOrtizFFairbanksL, et al.Younger age of dementia diagnosis in a Hispanic population in southern California. Int J Geriatr Psychiatry. 2014;29(6):586–593.
26.
O’BryantSEJohnsonLBalldinV, et al.Characterization of Mexican Americans with mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2013;33(2):373–379.
27.
SalazarRRoyallDRPalmerRF. Neuropsychiatric symptoms in community-dwelling Mexican-Americans: results from the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) study. Int J Geriatr Psychiatry. 2015;30(3):300–307.
28.
CohenCIMagaiC. Racial differences in neuropsychiatric symptoms among dementia outpatients. Am J Geriatr Psychiatry. 1999;7(1):57–63.
29.
OrtizFFittenLJCummingsJLHwangSFonsecaM. Neuropsychiatric and behavioral symptoms in a community sample of Hispanics with Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2006;21(4):263–273.
30.
RoyallDRPalmerRF; Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Texas Alzheimer’s Research and Care Consortium (TARCC). Selection for depression-specific dementia cases with replication in two cohorts. PLoS One. 2019;14(5):e0216413.
31.
WaringSO’BryantSEReischJDiaz-ArrastiaRKneblJDoodyR. The Texas Alzheimer’s Research Consortium longitudinal research cohort: study design and baseline characteristics. JTPHA. 2008;63(3):9–13.
32.
McKhannGDrachmanDFolsteinMKatzmanRPriceDStadlanEM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984;34(7):939–944.
33.
PetersenRC. Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004;256(3):183–194.
NgTPFengLNyuntMS, et al.Metabolic syndrome and the risk of mild cognitive impairment and progression to dementia: follow-up of the Singapore Longitudinal Ageing Study Cohort. JAMA Neurol. 2016;73(4):456–463.
36.
YaoQJiangGXZhouZMChenJMChengQ. Metabolic syndrome and mild cognitive impairment: a case-control study among elderly in a Shanghai suburb. J Alzheimers Dis. 2016;51(4):1175–1182.
37.
SanderlinAHTodemDBozokiAC. Obesity and co-morbid conditions are associated with specific neuropsychiatric symptoms in mild cognitive impairment. Front Aging Neurosci. 2017;9:164.
38.
ChaventMKuentz-SimonetVLiquetBSaraccoJ. ClustOfVar: an R package for the clustering of variables. J Stat Softw. 2012;50(13):16.
39.
KolenikovSAngelesG. The Use of Discrete Data in PCA: Theory, Simulations, and Applications to Socioeconomic Indices. Carolina Population Center, University of North Carolina; 2004:1–59. Vol. 20.
40.
SantosRDOGorgulhoBMCastroMADFisbergRMMarchioniDMBaltarVT. Principal component analysis and factor analysis: differences and similarities in nutritional epidemiology application. Revista Brasileira de Epidemiologia. 2019;22(2):e190041.
41.
DwivediAKShuklaR. Evidence-based statistical analysis and methods in biomedical research (SAMBR) checklists according to design features. Cancer Rep. n/a(n/a):e1211.
42.
AaltenPVerheyFRBozikiM, et al.Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord. 2007;24(6):457–463.
43.
HollingworthPHamshereMLMoskvinaV, et al.Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer’s disease. J Am Geriatr Soc. 2006;54(9):1348–1354.
44.
SchreinzerDBallabanTBrannathW, et al.Components of behavioral pathology in dementia. Int J Geriatr Psychiatry. 2005;20(2):137–145.
45.
KangHSAhnISKimJHKimDK. Neuropsychiatric symptoms in Korean patients with Alzheimer’s disease: exploratory factor analysis and confirmatory factor analysis of the Neuropsychiatric Inventory. Dement Geriatr Cogn Disord. 2010;29(1):82–87.
46.
SpallettaGMusiccoMPadovaniA, et al.Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease. Am J Geriatr Psychiatry. 2010;18(11):1026–1035.
47.
DechampsAJutandMAOnifadeCRichard-HarstonSBourdel-MarchassonI. Co-occurrence of neuropsychiatric syndromes in demented and psychotic institutionalized elderly. Int J Geriatr Psychiatry. 2008;23(11):1182–1190.
48.
DonovanNJAmariglioREZollerAS, et al.Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease. Am J Geriatr Psychiatry. 2014;22(12):1642–1651.
49.
LyketsosCGLopezOJonesBFitzpatrickALBreitnerJDeKoskyS. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002;288(12):1475–1483.
50.
IsmailZSmithEEGedaY, et al.Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2016;12(2):195–202.
51.
CreeseBBrookerHIsmailZ, et al.Mild behavioral impairment as a marker of cognitive decline in cognitively normal older adults. Am J Geriatr Psychiatry. 2019;27(8):823–834.
52.
VegaIECabreraLYWygantCMVelez-OrtizDCountsSE. Alzheimer’s Disease in the Latino community: intersection of genetics and social determinants of health. J Alzheimers Dis. 2017;58(4):979–992.
53.
HargraveRStoeklinMHaanMReedB. Clinical aspects of dementia in African-American, Hispanic, and white patients. J Natl Med Assoc. 2000;92(1):15–21.
54.
FittenLJOrtizFPontonM. Frequency of Alzheimer’s disease and other dementias in a community outreach sample of Hispanics. J Am Geriatr Soc. 2001;49(10):1301–1308.
55.
ChenJCBorsonSScanlanJM. Stage-specific prevalence of behavioral symptoms in Alzheimer’s disease in a multi-ethnic community sample. Am J Geriatr Psychiatry. 2000;8(2):123–133.
56.
O’BryantSEJohnsonLReischJ, et al.Risk factors for mild cognitive impairment among Mexican Americans. Alzheimers Dement. 2013;9(6):622–631. e621.
57.
BurkeSLNasehMRodriguezMJBurgessALoewensteinD. Dementia-related neuropsychological testing considerations in non-Hispanic white and Latino/Hispanic populations. Psychol Neurosci. 2019;12(2):144–168.
58.
HeJFariasSMartinezOReedBMungasDDecarliC. Differences in brain volume, hippocampal volume, cerebrovascular risk factors, and apolipoprotein E4 among mild cognitive impairment subtypes. Arch Neurol. 2009;66(11):1393–1399.
59.
Fernandez-MartinezMCastroJMolanoAZarranzJJRodrigoRMOrtegaR. Prevalence of neuropsychiatric symptoms in Alzheimer’s disease and vascular dementia. Curr Alzheimer Res. 2008;5(1):61–69.
60.
FilshteinTJDuggerBNJinLW, et al.Neuropathological diagnoses of demented Hispanic, black, and non-Hispanic white decedents seen at an Alzheimer’s disease center. J Alzheimers Dis. 2019;68(1):145–158.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
