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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition in a Sample of Community-dwelling Older Adults with Dementia

Author(s): Anton J. Kociolek, Kayri K. Fernandez, Michelle Hernandez, Zhezhen Jin, Stephanie Cosentino, Carolyn W. Zhu, Yian Gu, Davangere P. Devanand and Yaakov Stern*

Volume 20, Issue 6, 2023

Published on: 22 September, 2023

Page: [409 - 419] Pages: 11

DOI: 10.2174/1567205020666230908163414

Price: $65

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Abstract

Background and Objectives: Neuropsychiatric symptoms (NPS), including psychotic symptoms (hallucinations, illusions, delusions), agitation/aggression, and depressed mood, are common in individuals with Alzheimer’s disease (AD) and predict poorer outcomes, including faster disease progression. We aimed to evaluate associations between NPS and cognition and dependence in a multi-ethnic sample of community-dwelling older adults with AD.

Methods: Predictors 3 (P3) is a cohort study of AD disease courses recruiting older adults aged 65 and above residing in upper Manhattan. A total of 138 of 293 participants had probable AD at the study baseline. We fit linear mixed models to examine longitudinal associations of time-varying NPS (psychotic symptoms, agitation/aggression, and depressed mood) with dependence and cognition, adjusted for race-ethnicity, sex, education, age, clinical dementia rating score, APOE-ε4, and comorbidity burden; separate interaction models were fit for age, Hispanic ethnicity, and sex.

Results: Psychotic symptoms were associated with faster rates of increasing dependence and declining cognition over time, agitation/aggression with faster rates of declining cognition, and depressed mood with faster rates of increasing dependence. Among psychotic symptoms, delusions, but not hallucinations or illusions, were associated with worse outcome trajectories. Depressed mood predicted an accelerated increase in dependence in males but not females.

Conclusion: Our results confirm and extend prior results in clinic-based samples. The presence of NPS was associated with worse trajectories of dependence and cognition in this muti-ethnic sample of older adults with AD. Importantly, sex modified the association between depressed mood and dependence. Our results on NPS as predictors of differential AD progression in a community-dwelling, ethnically diverse sample serve to better inform the clinical care of patients and the future development of AD therapies.

[1]
Lyketsos, C.G.; Carrillo, M.C.; Ryan, J.M.; Khachaturian, A.S.; Trzepacz, P.; Amatniek, J.; Cedarbaum, J.; Brashear, R.; Miller, D.S. Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimers Dement., 2011, 7(5), 532-539.
[http://dx.doi.org/10.1016/j.jalz.2011.05.2410] [PMID: 21889116]
[2]
Lyketsos, C.G.; Lopez, O.; Jones, B.; Fitzpatrick, A.L.; Breitner, J.; DeKosky, S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA, 2002, 288(12), 1475-1483.
[http://dx.doi.org/10.1001/jama.288.12.1475] [PMID: 12243634]
[3]
Cummings, J. The role of neuropsychiatric symptoms in research diagnostic criteria for neurodegenerative diseases. Am. J. Geriatr. Psychiatry, 2021, 29(4), 375-383.
[http://dx.doi.org/10.1016/j.jagp.2020.07.011] [PMID: 32819825]
[4]
Papma, JM; Franzen, S; Swieten, JC; Ossenkoppele, R; Coesmans, M; Berg, E [P1–311]: The role of neuropsychiatric symptoms in ad differential diagnosis. Alzheimers Dement., 2017, 13(7S_Part_7), P372-P373.
[5]
Spalletta, G.; Long, J.D.; Robinson, R.G.; Trequattrini, A.; Pizzoli, S.; Caltagirone, C.; Orfei, M.D. Longitudinal neuropsychiatric predictors of death in alzheimer’s disease. J. Alzheimers Dis., 2015, 48(3), 627-636.
[http://dx.doi.org/10.3233/JAD-150391] [PMID: 26402103]
[6]
Zahodne, L.B.; Ornstein, K.; Cosentino, S.; Devanand, D.P.; Stern, Y. Longitudinal relationships between Alzheimer disease progression and psychosis, depressed mood, and agitation/aggression. Am. J. Geriatr. Psychiatry, 2015, 23(2), 130-140.
[http://dx.doi.org/10.1016/j.jagp.2013.03.014] [PMID: 23871118]
[7]
Gottesman, R.T.; Kociolek, A.; Fernandez, K.; Cosentino, S.; Devanand, D.P.; Stern, Y.; Gu, Y. Association between early psychotic symptoms and alzheimer’s disease prognosis in a community-based cohort. J. Alzheimers Dis., 2021, 81(3), 1131-1139.
[http://dx.doi.org/10.3233/JAD-200729] [PMID: 33896840]
[8]
Forester, B.P.; Vahia, I. Behavioral and psychological symptoms—an emerging crisis of the alzheimer dementia epidemic. JAMA Netw. Open, 2019, 2(3), e190790.
[http://dx.doi.org/10.1001/jamanetworkopen.2019.0790] [PMID: 30901037]
[9]
Gottesman, R.T.; Stern, Y. Behavioral and psychiatric symptoms of dementia and rate of decline in alzheimer’s disease. Front. Pharmacol., 2019, 10, 1062.
[http://dx.doi.org/10.3389/fphar.2019.01062] [PMID: 31616296]
[10]
Wilson, R.S.; Tang, Y.; Aggarwal, N.T.; Gilley, D.W.; McCann, J.J.; Bienias, J.L.; Evans, D.A. Hallucinations, cognitive decline, and death in Alzheimer’s disease. Neuroepidemiology., 2006, 26(2), 68-75.
[http://dx.doi.org/10.1159/000090251] [PMID: 16352909]
[11]
Connors, M.H.; Ames, D.; Woodward, M.; Brodaty, H. Psychosis and clinical outcomes in alzheimer disease: A longitudinal study. Am. J. Geriatr. Psychiatry, 2018, 26(3), 304-313.
[http://dx.doi.org/10.1016/j.jagp.2017.10.011] [PMID: 29174998]
[12]
Hallikainen, I.; Koivisto, A.M.; Välimäki, T. The influence of the individual neuropsychiatric symptoms of people with Alzheimer disease on family caregiver distress-A longitudinal ALSOVA study. Int. J. Geriatr. Psychiatry, 2018, 33(9), 1207-1212.
[http://dx.doi.org/10.1002/gps.4911] [PMID: 29851148]
[13]
Herrmann, N.; Lanctôt, K.L.; Sambrook, R.; Lesnikova, N.; Hébert, R.; McCracken, P.; Robillard, A.; Nguyen, E. The contribution of neuropsychiatric symptoms to the cost of dementia care. Int. J. Geriatr. Psychiatry, 2006, 21(10), 972-976.
[http://dx.doi.org/10.1002/gps.1594] [PMID: 16955429]
[14]
Murman, D.L.; Chen, Q.; Powell, M.C.; Kuo, S.B.; Bradley, C.J.; Colenda, C.C. The incremental direct costs associated with behavioral symptoms in AD. Neurology, 2002, 59(11), 1721-1729.
[http://dx.doi.org/10.1212/01.WNL.0000036904.73393.E4] [PMID: 12473759]
[15]
Iravani, B.; Abdollahi, E.; Eslamdoust-Siahestalkhi, F.; Soleimani, R. Neuropsychiatric symptoms of alzheimer’s disease and caregiver burden. Front. Neurol., 2022, 13, 877143.
[http://dx.doi.org/10.3389/fneur.2022.877143] [PMID: 35968317]
[16]
Devanand, D.P. The interrelations between psychosis, behavioral disturbance, and depression in Alzheimer disease. Alzheimer Dis. Assoc. Disord., 1999, 13(S2), S3-S8.
[PMID: 10622673]
[17]
Dilworth-Anderson, P.; Hendrie, H.C.; Manly, J.J.; Khachaturian, A.S.; Fazio, S.; Social, B. Diagnosis and assessment of Alzheimer’s disease in diverse populations. Alzheimers Dement., 2008, 4(4), 305-309.
[http://dx.doi.org/10.1016/j.jalz.2008.03.001] [PMID: 18631983]
[18]
Morris, J.C.; Schindler, S.E.; McCue, L.M.; Moulder, K.L.; Benzinger, T.L.S.; Cruchaga, C.; Fagan, A.M.; Grant, E.; Gordon, B.A.; Holtzman, D.M.; Xiong, C. Assessment of racial disparities in biomarkers for alzheimer disease. JAMA Neurol., 2019, 76(3), 264-273.
[http://dx.doi.org/10.1001/jamaneurol.2018.4249] [PMID: 30615028]
[19]
Gottesman, R.F.; Schneider, A.L.C.; Zhou, Y.; Chen, X.; Green, E.; Gupta, N.; Knopman, D.S.; Mintz, A.; Rahmim, A.; Sharrett, A.R.; Wagenknecht, L.E.; Wong, D.F.; Mosley, T.H., Jr The ARIC-PET amyloid imaging study. Neurology, 2016, 87(5), 473-480.
[http://dx.doi.org/10.1212/WNL.0000000000002914] [PMID: 27371485]
[20]
Gavett, B.E.; Fletcher, E.; Harvey, D.; Farias, S.T.; Olichney, J.; Beckett, L.; DeCarli, C.; Mungas, D. Ethnoracial differences in brain structure change and cognitive change. Neuropsychology., 2018, 32(5), 529-540.
[http://dx.doi.org/10.1037/neu0000452] [PMID: 29648842]
[21]
Stern, Y. Cognitive reserve in ageing and Alzheimer’s disease. Lancet Neurol., 2012, 11(11), 1006-1012.
[http://dx.doi.org/10.1016/S1474-4422(12)70191-6] [PMID: 23079557]
[22]
Scarmeas, N.; Albert, S.M.; Manly, J.J.; Stern, Y. Education and rates of cognitive decline in incident Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry, 2005, 77(3), 308-316.
[http://dx.doi.org/10.1136/jnnp.2005.072306] [PMID: 16484637]
[23]
Levine, D.A.; Gross, A.L.; Briceño, E.M.; Tilton, N.; Giordani, B.J.; Sussman, J.B.; Hayward, R.A.; Burke, J.F.; Hingtgen, S.; Elkind, M.S.V.; Manly, J.J.; Gottesman, R.F.; Gaskin, D.J.; Sidney, S.; Sacco, R.L.; Tom, S.E.; Wright, C.B.; Yaffe, K.; Galecki, A.T. Sex differences in cognitive decline among US adults. JAMA Netw. Open, 2021, 4(2), e210169.
[http://dx.doi.org/10.1001/jamanetworkopen.2021.0169] [PMID: 33630089]
[24]
Bernick, C.; Cummings, J.; Raman, R.; Sun, X.; Aisen, P. Age and rate of cognitive decline in Alzheimer disease: Implications for clinical trials. Arch. Neurol., 2012, 69(7), 901-905.
[http://dx.doi.org/10.1001/archneurol.2011.3758] [PMID: 22431834]
[25]
Lennon, J.C.; Aita, S.L.; Bene, V.A.D.; Rhoads, T.; Resch, Z.J.; Eloi, J.M. Black and White individuals differ in dementia prevalence, risk factors, and symptomatic presentation. Alzheimers Dement., 2021, 18(8), 1461-1471.
[PMID: 34854531]
[26]
Tang, M.X.; Cross, P.; Andrews, H.; Jacobs, D.M.; Small, S.; Bell, K.; Merchant, C.; Lantigua, R.; Costa, R.; Stern, Y.; Mayeux, R. Incidence of AD in African-Americans, caribbean hispanics, and caucasians in northern Manhattan. Neurology., 2001, 56(1), 49-56.
[http://dx.doi.org/10.1212/WNL.56.1.49] [PMID: 11148235]
[27]
Chen, C.; Zissimopoulos, J.M. Racial and ethnic differences in trends in dementia prevalence and risk factors in the United States. Alzheimers Dement., 2018, 4(1), 510-520.
[http://dx.doi.org/10.1016/j.trci.2018.08.009] [PMID: 30364652]
[28]
Schwartz, J.B.; Weintraub, S. Treatment for alzheimer disease- sex and gender effects need to be explicitly analyzed and reported in clinical trials. JAMA Netw. Open, 2021, 4(9), e2124386.
[http://dx.doi.org/10.1001/jamanetworkopen.2021.24386] [PMID: 34515788]
[29]
Babulal, G.M.; Quiroz, Y.T.; Albensi, B.C.; Arenaza-Urquijo, E.; Astell, A.J.; Babiloni, C.; Bahar-Fuchs, A.; Bell, J.; Bowman, G.L.; Brickman, A.M.; Chételat, G.; Ciro, C.; Cohen, A.D.; Dilworth-Anderson, P.; Dodge, H.H.; Dreux, S.; Edland, S.; Esbensen, A.; Evered, L.; Ewers, M.; Fargo, K.N.; Fortea, J.; Gonzalez, H.; Gustafson, D.R.; Head, E.; Hendrix, J.A.; Hofer, S.M.; Johnson, L.A.; Jutten, R.; Kilborn, K.; Lanctôt, K.L.; Manly, J.J.; Martins, R.N.; Mielke, M.M.; Morris, M.C.; Murray, M.E.; Oh, E.S.; Parra, M.A.; Rissman, R.A.; Roe, C.M.; Santos, O.A.; Scarmeas, N.; Schneider, L.S.; Schupf, N.; Sikkes, S.; Snyder, H.M.; Sohrabi, H.R.; Stern, Y.; Strydom, A.; Tang, Y.; Terrera, G.M.; Teunissen, C.; Melo van Lent, D.; Weinborn, M.; Wesselman, L.; Wilcock, D.M.; Zetterberg, H.; O’Bryant, S.E. Perspectives on ethnic and racial disparities in Alzheimer’s disease and related dementias: Update and areas of immediate need. Alzheimers Dement., 2019, 15(2), 292-312.
[http://dx.doi.org/10.1016/j.jalz.2018.09.009] [PMID: 30555031]
[30]
Vespa, J; Armstrong, DM; Medina, L; Bureau, USC Demographic turning points for the United States: Population projections for 2020 to 2060 Report Number P25-1144, 2018.
[31]
Devi, G.; Scheltens, P. Heterogeneity of Alzheimer’s disease: Consequence for drug trials? Alzheimers Res. Ther., 2018, 10(1), 122.
[http://dx.doi.org/10.1186/s13195-018-0455-y] [PMID: 30567585]
[32]
Stern, Y.; Gu, Y.; Cosentino, S.; Azar, M.; Lawless, S.; Tatarina, O. The predictors study: Development and baseline characteristics of the Predictors 3 cohort. Alzheimers Dement., 2017, 13(1), 20-27.
[http://dx.doi.org/10.1016/j.jalz.2016.04.004] [PMID: 27219818]
[33]
Manly, J.J.; Bell-McGinty, S.; Tang, M.X.; Schupf, N.; Stern, Y.; Mayeux, R. Implementing diagnostic criteria and estimating frequency of mild cognitive impairment in an urban community. Arch. Neurol., 2005, 62(11), 1739-1746.
[http://dx.doi.org/10.1001/archneur.62.11.1739] [PMID: 16286549]
[34]
McKhann, G.; Drachman, D.; Folstein, M.; Katzman, R.; Price, D.; Stadlan, E.M. 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.
[http://dx.doi.org/10.1212/WNL.34.7.939] [PMID: 6610841]
[35]
Zhu, C.W.; Bruinsma, B.G.; Stern, Y. Utility of the dependence scale in dementia: Validity, meaningfulness, and health economic considerations. Alzheimers Res. Ther., 2018, 10(1), 78.
[http://dx.doi.org/10.1186/s13195-018-0414-7] [PMID: 30103820]
[36]
Stern, Y.; Sano, M.; Paulson, J.; Mayeux, R.P. Modified mini-mental state examination: Validity and reliability. Neurology, 1987, 37.
[37]
Devanand, D.P. Use of the columbia university scale to assess psychopathology in alzheimer’s disease. Int. Psychogeriatr., 1997, 9(S1), 137-142.
[http://dx.doi.org/10.1017/S104161029700481X] [PMID: 9447437]
[38]
Stern, Y.; Albert, M.; Brandt, J.; Jacobs, D.M.; Tang, M-X.; Marder, K.; Bell, K.; Sano, M.; Devanand, D.P.; Bylsma, F.; Lafleche, G. Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer’s disease: Prospective analyses from the Predictors Study. Neurology, 1994, 44(12), 2300-2307.
[http://dx.doi.org/10.1212/WNL.44.12.2300] [PMID: 7991116]
[39]
Gu, Y.; Gutierrez, J.; Meier, I.B.; Guzman, V.A.; Manly, J.J.; Schupf, N.; Brickman, A.M.; Mayeux, R. Circulating inflammatory biomarkers are related to cerebrovascular disease in older adults. Neurol. Neuroimmunol. Neuroinflamm., 2019, 6(1), e521.
[http://dx.doi.org/10.1212/NXI.0000000000000521] [PMID: 30568999]
[40]
Kociolek, A.J.; Fernandez, K.K.; Jin, Z.; Cosentino, S.; Zhu, C.W.; Gu, Y.; Stern, Y. Extrapyramidal signs and Alzheimer’s disease prognosis in a multiethnic, community-based sample of demented elders. Alzheimers Dement., 2021, 17(9), 1465-1473.
[http://dx.doi.org/10.1002/alz.12309] [PMID: 33710771]
[41]
Team, RC.R A language and environment for statistical computing. In: R Foundation for Statistical Computing, Vienna, Austria; , 2020.
[42]
Team, R.S. RStudio: Integrated Development for R;
[43]
Cole, S.R.; Hernán, M.A. Constructing inverse probability weights for marginal structural models. Am. J. Epidemiol, 2008, 168(6), 656-664.
[44]
van der Wal, W.M.; Geskus, R.B. {ipw}: An {R} package for inverse probability weighting. J. Stat. Softw., 2011, 43(13), 1-23.
[45]
Kuhn, M. caret: Classification and Regression Training; Astrophysics Source Code Library, 2021.
[46]
Bates, D.; Mächler, M.; Bolker, B.; Walker, S. Fitting linear mixed-effects models using lme4. J. Stat. Softw., 2015, 67(1), 1-48.
[http://dx.doi.org/10.18637/jss.v067.i01]
[47]
Twisk, J.W.R. Applied longitudinal data analysis for epidemiology: a practical guide; Cambridge University Press: Cambridge, New York, 2015.
[48]
Scarmeas, N.; Brandt, J.; Albert, M.; Hadjigeorgiou, G.; Papadimitriou, A.; Dubois, B.; Sarazin, M.; Devanand, D.; Honig, L.; Marder, K.; Bell, K.; Wegesin, D.; Blacker, D.; Stern, Y. Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Arch. Neurol., 2005, 62(10), 1601-1608.
[http://dx.doi.org/10.1001/archneur.62.10.1601] [PMID: 16216946]
[49]
Stern, Y. Cognitive reserve and Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2006, 20(2), 112-117.
[http://dx.doi.org/10.1097/01.wad.0000213815.20177.19] [PMID: 16772747]
[50]
Manly, J.M.R. Ethnic differences in dementia and Alzheimer’sdisease. In: Critical Perspectives on Racial and Ethnic Differences in Health in Late Life; National Academies Press, 2004.
[51]
Sisco, S.; Gross, A.L.; Shih, R.A.; Sachs, B.C.; Glymour, M.M.; Bangen, K.J.; Benitez, A.; Skinner, J.; Schneider, B.C.; Manly, J.J. The role of early-life educational quality and literacy in explaining racial disparities in cognition in late life. J. Gerontol. B Psychol. Sci. Soc. Sci., 2015, 70(4), 557-567.
[http://dx.doi.org/10.1093/geronb/gbt133] [PMID: 24584038]
[52]
Matthews, K.A.; Xu, W.; Gaglioti, A.H.; Holt, J.B.; Croft, J.B.; Mack, D.; McGuire, L.C. Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimers Dement., 2019, 15(1), 17-24.
[http://dx.doi.org/10.1016/j.jalz.2018.06.3063] [PMID: 30243772]
[53]
Russell, J.K.; Jones, C.K.; Newhouse, P.A. The role of estrogen in brain and cognitive aging. Neurotherapeutics, 2019, 16(3), 649-665.
[http://dx.doi.org/10.1007/s13311-019-00766-9] [PMID: 31364065]
[54]
Schofield, P.W.; Tang, M.; Marder, K.; Bell, K.; Dooneief, G.; Lantigua, R.; Wilder, D.; Gurland, B.; Stern, Y.; Mayeux, R. Consistency of clinical diagnosis in a community-based longitudinal study of dementia and Alzheimer’s disease. Neurology, 1995, 45(12), 2159-2164.
[http://dx.doi.org/10.1212/WNL.45.12.2159] [PMID: 8848185]

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