Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

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

Research Article

Assessing the Stability of Clusters of Neuropsychiatric Symptoms in Alzheimer’s Disease and Mild Cognitive Impairment

In Press, (this is not the final "Version of Record"). Available online 15 July, 2024
Author(s): Sara Scarfo, Yashar Moshfeghi and William J. McGeown*
Published on: 15 July, 2024

DOI: 10.2174/0115672050309014240705113444

Price: $95

Abstract

Aim: The aim of the study was to investigate the factors that underpin neuropsychiatric symptoms and how they might evolve over time in people with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD) dementia.

Background: Neuropsychiatric symptoms are psychiatric and behavioural manifestations that occur in people with AD. These are highly prevalent along the continuum of the disease, including at the stage of MCI, as well as before cognitive decline. Various small- and large-scale projects have investigated the underlying factors that underpin these symptoms; however, the identification of clear clusters is still a matter of debate; furthermore, no study has investigated how the clusters might change across the development of AD pathology by comparing different time points.

Objective: Our objective was to investigate the factors that underpin neuropsychiatric symptoms in Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) and to assess how the loadings might differ based on considerations such as the disease stage of the samples.

Methods: Data was obtained from the Alzheimer’s Disease Neuroimaging Initiative database (adni. loni.usc.edu), using scores from the Neuropsychiatric Inventory, followed up yearly from baseline until month 72. Participant groups included those with MCI or AD dementia, or a mixture of both, with all participants presenting with at least one neuropsychiatric symptom. A series of exploratory Principal Component and Factor (Principal Axis) Analyses were performed using Direct Oblimin rotation.

Results: The best-fitting structure was interpreted for each time point. A consistent, unique structure could not be identified, as the factors were unstable over time, both within the MCI and AD groups. However, some symptoms showed a tendency to load on the same factors across most measurements (i.e., agitation with irritability, depression with anxiety, elation with disinhibition, delusions with hallucinations).

Conclusion: Although the analyses revealed some degree of co-occurrence of neuropsychiatric symptoms across time points/samples, there was also considerable variation. In the AD group, more discrete syndromes were evident at the early time points, whereas a more complex picture of co-occurring symptoms, with differences likely reflecting disease staging, was seen at later time points. As a clear and distinctive factor structure was not consistently identified across time points/ samples, this highlights the potential importance of sample selection (e.g., disease stage and/or heterogeneity) when studying, for example, the neurobiological underpinnings of neuropsychiatric symptoms.

[1]
Steinberg M, Shao H, Zandi P, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: The cache county study. Int J Geriatr Psychiatry 2008; 23(2): 170-7.
[http://dx.doi.org/10.1002/gps.1858] [PMID: 17607801]
[2]
Gallagher D, Fischer CE, Iaboni A. Neuropsychiatric symptoms in mild cognitive impairment. Can J Psychiatry 2017; 62(3): 161-9.
[http://dx.doi.org/10.1177/0706743716648296] [PMID: 28212495]
[3]
Ismail Z, Creese B, Aarsland D, et al. Psychosis in Alzheimer disease mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol 2022; 18(3): 131-44.
[http://dx.doi.org/10.1038/s41582-021-00597-3] [PMID: 34983978]
[4]
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44(12): 2308-14.
[http://dx.doi.org/10.1212/WNL.44.12.2308] [PMID: 7991117]
[5]
Peters ME, Schwartz S, Han D, et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: the Cache County Dementia Progression Study. Am J Psychiatry 2015; 172(5): 460-5.
[http://dx.doi.org/10.1176/appi.ajp.2014.14040480] [PMID: 25585033]
[6]
Poulin SP, Bergeron D, Dickerson BC. Risk factors, neuroanatomical correlates, and outcome of neuropsychiatric symptoms in alzheimer’s disease. J Alzheimers Dis 2017; 60(2): 483-93.
[http://dx.doi.org/10.3233/JAD-160767] [PMID: 28869463]
[7]
Zhao QF, Tan L, Wang HF, et al. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: Systematic review and meta-analysis. J Affect Disord 2016; 190: 264-71.
[http://dx.doi.org/10.1016/j.jad.2015.09.069] [PMID: 26540080]
[8]
Geda YE, Schneider LS, Gitlin LN, et al. Neuropsychiatric symptoms in Alzheimer’s disease: Past progress and anticipation of the future. Alzheimers Dement 2013; 9(5): 602-8.
[http://dx.doi.org/10.1016/j.jalz.2012.12.001] [PMID: 23562430]
[9]
Hiu SKW, Bigirumurame T, Kunonga P, Bryant A, Pillai M. Neuropsychiatric Inventory domains cluster into neuropsychiatric syndromes in Alzheimer’s disease: A systematic review and meta-analysis. Brain Behav 2022; 12(9): e2734.
[http://dx.doi.org/10.1002/brb3.2734] [PMID: 35939055]
[10]
Gottesman RT, 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]
[11]
Watkins MW. Exploratory factor analysis: A guide to best practice. J Black Psychol 2018; 44(3): 219-46.
[http://dx.doi.org/10.1177/0095798418771807]
[12]
Cheng ST, Kwok T, Lam LCW. Neuropsychiatric symptom clusters of Alzheimer’s disease in Hong Kong Chinese: prevalence and confirmatory factor analysis of the Neuropsychiatric Inventory. Int Psychogeriatr 2012; 24(9): 1465-73.
[http://dx.doi.org/10.1017/S1041610212000609] [PMID: 22717370]
[13]
Apostolova LG, Di LJ, Duffy EL, et al. Risk factors for behavioral abnormalities in mild cognitive impairment and mild Alzheimer’s disease. Dement Geriatr Cogn Disord 2014; 37(5-6): 315-26.
[http://dx.doi.org/10.1159/000351009] [PMID: 24481207]
[14]
Aalten P, Verhey FRJ, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease Consortium: part I. Dement Geriatr Cogn Disord 2007; 24(6): 457-63.
[http://dx.doi.org/10.1159/000110738] [PMID: 17986816]
[15]
Hollingworth P, Hamshere ML, Moskvina V, et al. Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer’s disease. J Am Geriatr Soc 2006; 54(9): 1348-54.
[http://dx.doi.org/10.1111/j.1532-5415.2006.00854.x] [PMID: 16970641]
[16]
Kang HS, Ahn IS, Kim JH, Kim DK. 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): 82-7.
[http://dx.doi.org/10.1159/000264629] [PMID: 20130406]
[17]
Nagata T, Shinagawa S, Nakajima S, et al. Classification of neuropsychiatric symptoms requiring antipsychotic treatment in patients with alzheimer’s disease: Analysis of the CATIE-AD Study. J Alzheimers Dis 2016; 50(3): 839-45.
[http://dx.doi.org/10.3233/JAD-150869] [PMID: 26836181]
[18]
De Vito AN, Calamia M, Weitzner DS, Bernstein JPK. Examining differences in neuropsychiatric symptom factor trajectories in empirically derived mild cognitive impairment subtypes. Int J Geriatr Psychiatry 2018; 33(12): 1627-34.
[http://dx.doi.org/10.1002/gps.4963] [PMID: 30276884]
[19]
Wadsworth LP, Lorius N, Donovan NJ, et al. Neuropsychiatric symptoms and global functional impairment along the Alzheimer’s continuum. Dement Geriatr Cogn Disord 2012; 34(2): 96-111.
[http://dx.doi.org/10.1159/000342119] [PMID: 22922821]
[20]
Edwards ER, Spira AP, Barnes DE, Yaffe K. Neuropsychiatric symptoms in mild cognitive impairment: differences by subtype and progression to dementia. Int J Geriatr Psychiatry 2009; 24(7): 716-22.
[http://dx.doi.org/10.1002/gps.2187] [PMID: 19140134]
[21]
Alzheimer’s Disease Neuroimaging Initiative. ADNI | Alzheimer's Disease Neuroimaging Initiative (usc.edu). 2022. Available from: http://adni.loni.usc.edu/
[24]
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. J Psychiatr Res 1975; 12(3): 189-98.
[http://dx.doi.org/10.1016/0022-3956(75)90026-6] [PMID: 1202204]
[25]
Berg L. Clinical Dementia Rating (CDR). Psychopharmacol Bull 1988; 24(4): 637-9.
[PMID: 3249765]
[26]
Costello AB, Osborne J. Best practices in exploratory factor analysis: four recommendations for getting the most from your analysis. Pract Assess, Res Eval 2005; 10: 1-9.
[27]
Stevens JP. Applied multivariate statistics for the social sciences. (4th ed.), Mahwah, NJ, US: Lawrence Erlbaum Associates Publishers 2002.
[28]
Kaiser HF. An index of factorial simplicity. Psychometrika 1974; 39(1): 31-6.
[http://dx.doi.org/10.1007/BF02291575]
[29]
Bartlett MS. A note on the multiplying factors for various chi square approximations. J R Stat Soc Series B Stat Methodol 1954; 16(2): 296-8.
[http://dx.doi.org/10.1111/j.2517-6161.1954.tb00174.x]
[30]
Corp IBM. IBM SPSS Statistics for Windows. Armonk, NY: IBM Corp 2021. Internet [Available from: https://www.ibm.com/support/pages/how-cite-ibm-spss-statistics-or-earlier-versions-spss]
[31]
Tabachnick BG, Fidell LS. Using Multivariate Statistics. (5th ed.), Allyn & Bacon, Inc. 2006.
[32]
Kaiser HF. The Application of Electronic Computers to Factor Analysis. Educ Psychol Meas 1960; 20(1): 141-51.
[http://dx.doi.org/10.1177/001316446002000116]
[33]
Cattell RB. The scree test for the number of factors. Multivariate Behav Res 1966; 1(2): 245-76.
[http://dx.doi.org/10.1207/s15327906mbr0102_10] [PMID: 26828106]
[34]
Ehrenberg AJ, Suemoto CK, França Resende EP, et al. Neuropathologic correlates of psychiatric symptoms in alzheimer’s disease. J Alzheimers Dis 2018; 66(1): 115-26.
[http://dx.doi.org/10.3233/JAD-180688] [PMID: 30223398]
[35]
Nelson RS, Abner EL, Jicha GA, et al. Neurodegenerative pathologies associated with behavioral and psychological symptoms of dementia in a community-based autopsy cohort. Acta Neuropathol Commun 2023; 11(1): 89.
[http://dx.doi.org/10.1186/s40478-023-01576-z] [PMID: 37269007]
[36]
Tu MC, Huang WH, Hsu YH, Lo CP, Deng JF, Huang CF. Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer’s disease. BMC Neurol 2017; 17(1): 144.
[http://dx.doi.org/10.1186/s12883-017-0911-5] [PMID: 28754095]
[37]
Bettney L, Butt S, Morris J, et al. Investigating the stability of neuropsychiatric sub-syndromes with progression of dementia: A 2-year prospective study. Int J Geriatr Psychiatry 2012; 27(11): 1118-23.
[http://dx.doi.org/10.1002/gps.2829] [PMID: 22250004]
[38]
Serra L, Bruschini M, Di Domenico C, et al. Behavioral psychological symptoms of dementia and functional connectivity changes: A network-based study. Neurobiol Aging 2020; 94: 196-206.
[http://dx.doi.org/10.1016/j.neurobiolaging.2020.06.009] [PMID: 32645548]
[39]
Garre-Olmo J, López-Pousa S, Vilalta-Franch J, de Gracia Blanco M, Vilarrasa AB. Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer’s disease, part I: symptom clusters. J Alzheimers Dis 2011; 22(4): 1157-67.
[http://dx.doi.org/10.3233/JAD-2010-101212] [PMID: 20930289]
[40]
Mirakhur A, Craig D, Hart DJ, Mcllroy SP, Passmore AP. Behavioural and psychological syndromes in Alzheimer’s disease. Int J Geriatr Psychiatry 2004; 19(11): 1035-9.
[http://dx.doi.org/10.1002/gps.1203] [PMID: 15481075]
[41]
Truzzi A, Ulstein I, Valente L, et al. Patterns of neuropsychiatric sub-syndromes in Brazilian and Norwegian patients with dementia. Int Psychogeriatr 2013; 25(2): 228-35.
[http://dx.doi.org/10.1017/S1041610212001640] [PMID: 23113901]
[42]
Groen RN, Ryan O, Wigman JTW, et al. Comorbidity between depression and anxiety: assessing the role of bridge mental states in dynamic psychological networks. BMC Med 2020; 18(1): 308.
[http://dx.doi.org/10.1186/s12916-020-01738-z] [PMID: 32988400]
[43]
Wu H, Cottingham C, Chen L, et al. Age-dependent differential regulation of anxiety and depression-related behaviors by neurabin and spinophilin. PLoS One 2017; 12(7): e0180638.
[http://dx.doi.org/10.1371/journal.pone.0180638] [PMID: 28700667]
[44]
Colombo M, Vitali S, Cairati M, Vaccaro R, Andreoni G, Guaita A. Behavioral and psychotic symptoms of dementia (BPSD) improvements in a special care unit: A factor analysis. Arch Gerontol Geriatr 2007; 44 (Suppl. 1): 113-20.
[http://dx.doi.org/10.1016/j.archger.2007.01.017] [PMID: 17317443]
[45]
Hartley S, Barrowclough C, Haddock G. Anxiety and depression in psychosis: A systematic review of associations with positive psychotic symptoms. Acta Psychiatr Scand 2013; 128(5): 327-46.
[http://dx.doi.org/10.1111/acps.12080] [PMID: 23379898]
[46]
Wilkosz PA, Kodavali C, Weamer EA, et al. Prediction of psychosis onset in Alzheimer disease: the role of depression symptom severity and the HTR2A T102C polymorphism. American journal of medical genetics. Part B, Neuropsychiatric genetics: the official publication of the International Society of Psychiatric Genetics 2007; 144B(8): 1054-62.
[47]
Wilkosz PA, Miyahara S, Lopez OL, Dekosky ST, Sweet RA. Prediction of psychosis onset in Alzheimer disease: The role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 2006; 14(4): 352-60.
[48]
Bassiony MM, Warren A, Rosenblatt A, et al. The relationship between delusions and depression in Alzheimer’s disease. Int J Geriatr Psychiatry 2002; 17(6): 549-56.
[http://dx.doi.org/10.1002/gps.641] [PMID: 12112179]
[49]
Mizrahi R, Starkstein SE, Jorge R, Robinson RG. Phenomenology and clinical correlates of delusions in Alzheimer disease. The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 2006; 14(7): 573-81.
[50]
Lanctôt KL, Agüera-Ortiz L, Brodaty H, et al. Apathy associated with neurocognitive disorders: Recent progress and future directions. Alzheimers Dement 2017; 13(1): 84-100.
[http://dx.doi.org/10.1016/j.jalz.2016.05.008] [PMID: 27362291]
[51]
Tascone LS, Bottino CMC. Neurobiology of neuropsychiatric symptoms in Alzheimer’s disease: A critical review with a focus on neuroimaging. Dement Neuropsychol 2013; 7(3): 236-43.
[http://dx.doi.org/10.1590/S1980-57642013DN70300002] [PMID: 29213845]
[52]
Lanctôt KL, Ismail Z, Bawa KK, et al. Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment-related aspects of apathy from depression in neurocognitive disorders. Int J Geriatr Psychiatry 2023; 38(2): e5882.
[http://dx.doi.org/10.1002/gps.5882] [PMID: 36739588]
[53]
Mortby ME, Adler L, Agüera-Ortiz L, et al. Apathy as a treatment target in alzheimer’s disease: Implications for clinical trials. Am J Geriatr Psychiatry 2022; 30(2): 119-47.
[http://dx.doi.org/10.1016/j.jagp.2021.06.016] [PMID: 34315645]
[54]
Mograbi DC, Morris RG. On the relation among mood, apathy, and anosognosia in Alzheimer’s disease. J Int Neuropsychol Soc 2014; 20(1): 2-7.
[http://dx.doi.org/10.1017/S1355617713001276] [PMID: 24331082]
[55]
Hollingworth P, Sweet R, Sims R, et al. Genome-wide association study of Alzheimer’s disease with psychotic symptoms. Mol Psychiatry 2012; 17(12): 1316-27.
[http://dx.doi.org/10.1038/mp.2011.125] [PMID: 22005930]
[56]
Fischer CE, Ismail Z, Youakim JM, et al. Revisiting criteria for psychosis in alzheimer’s disease and related dementias: Toward better phenotypic classification and biomarker research. J Alzheimers Dis 2020; 73(3): 1143-56.
[http://dx.doi.org/10.3233/JAD-190828] [PMID: 31884469]
[57]
Selbæk G, Engedal K. Stability of the factor structure of the Neuropsychiatric Inventory in a 31-month follow-up study of a large sample of nursing-home patients with dementia. Int Psychogeriatr 2012; 24(1): 62-73.
[http://dx.doi.org/10.1017/S104161021100086X] [PMID: 21682940]
[58]
Liu S, Wang X, Zheng Q, Gao L, Sun Q. Sleep deprivation and central appetite regulation. Nutrients 2022; 14(24): 5196.
[http://dx.doi.org/10.3390/nu14245196] [PMID: 36558355]
[59]
van der Linde RM, Dening T, Matthews FE, Brayne C. Grouping of behavioural and psychological symptoms of dementia. Int J Geriatr Psychiatry 2014; 29(6): 562-8.
[http://dx.doi.org/10.1002/gps.4037] [PMID: 24677112]
[60]
Reeve S, Sheaves B, Freeman D. The role of sleep dysfunction in the occurrence of delusions and hallucinations: A systematic review. Clin Psychol Rev 2015; 42: 96-115.
[http://dx.doi.org/10.1016/j.cpr.2015.09.001] [PMID: 26407540]
[61]
Benca R, Herring WJ, Khandker R, Qureshi ZP. Burden of insomnia and sleep disturbances and the impact of sleep treatments in patients with probable or possible alzheimer’s disease: A structured literature review. J Alzheimers Dis 2022; 86(1): 83-109.
[http://dx.doi.org/10.3233/JAD-215324] [PMID: 35001893]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy