Prevalence, Clinical Correlates, Cognitive Trajectories, and Dementia Risk Associated With Mild Behavioral Impairment in Asians

Cheuk Ni Kan, PDipPsych; Jemellee Cano, MD; Xuhao Zhao, MPH; Zahinoor Ismail, MD; Christopher Li-Hsian Chen, FRCP; Xin Xu, PhD

J Clin Psychiatry 2022;83(3):21m14105

ABSTRACT

Objective: Mild behavioral impairment (MBI) is characterized as later-life–emergent and persistent neuropsychiatric symptoms (NPS). The symptom persistence criterion of MBI has shown to increase the signal-to-noise ratio of the syndrome, decreasing the likelihood of false-positive NPS. However, the long-term cognitive and prognostic impact of MBI remains to be evaluated against the traditional framework of NPS, especially in Asian cohorts. This study investigated the epidemiologic characteristics of MBI in a prospective clinical cohort of Singaporean elderly.

Methods: A total of 304 dementia-free individuals (mean [SD] age = 72.2 [8.0] years, 51.6% female) were recruited between August 2010 and October 2019. All participants underwent annual neuropsychological, neuropsychiatric, and clinical assessments for 4 consecutive years and were diagnosed as having no cognitive impairment (NCI) or cognitive impairment–no dementia (CIND). MBI was ascertained using both baseline and year-1 Neuropsychiatric Inventory assessments. Cognitive Z-scores and Clinical Dementia Rating Sum-of-Boxes (CDR-SoB) scores were calculated.

Results: The prevalence of MBI was 14.5% (7.1% of NCI, 12.9% of CIND-mild, and 24.7% of CIND-moderate patients). MBI patients showed poorer cognitive function at baseline (F_1,295 = 8.13 [SE = 0.47], P = .005), primarily in memory and executive function domains. MBI was associated with accelerated decline in global cognition (β = –0.15; 95% CI, −0.23 to −0.07) along with faster increase in CDR-SoB (β = 0.92; 95% CI, 0.62 to 1.21) as compared to individuals without symptoms or transient NPS. A total of 38.6% of MBI patients developed dementia as compared to 12.3% of non-MBI elderly (χ² = 19.29, P < .001). MBI increased risk of incident dementia by 2.56-fold as compared to no symptoms or transient NPS, regardless of cognitive impairment.

Conclusions: MBI is a neurobehavioral risk factor for dementia, representing a potential target for dementia risk modeling, preventive intervention, and disease management.

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References (43)

Karttunen K, Karppi P, Hiltunen A, et al; ALSOVA study group. Neuropsychiatric symptoms and quality of life in patients with very mild and mild Alzheimer’s disease. Int J Geriatr Psychiatry. 2011;26(5):473–482. PubMed CrossRef
Pocnet C, Antonietti JP, Donati A, et al. Behavioral and psychological symptoms and cognitive decline in patients with amnestic MCI and mild AD: a two-year follow-up study. Int Psychogeriatr. 2015;27(8):1379–1389. PubMed CrossRef
Broomfield NM, Quinn TJ, Abdul-Rahim AH, et al. Depression and anxiety symptoms post-stroke/TIA: prevalence and associations in cross-sectional data from a regional stroke registry. BMC Neurol. 2014;14(1):198. PubMed CrossRef
Aalten P, de Vugt ME, Jaspers N, et al. The course of neuropsychiatric symptoms in dementia. Part I: findings from the two-year longitudinal Maasbed study. Int J Geriatr Psychiatry. 2005;20(6):523–530. PubMed CrossRef
Ryu SH, Ha JH, Park DH, et al. Persistence of neuropsychiatric symptoms over six months in mild cognitive impairment in community-dwelling Korean elderly. Int Psychogeriatr. 2011;23(2):214–220. PubMed CrossRef
Poulin SP, Bergeron D, Dickerson BC; Alzheimer’s Disease Neuroimaging Initiative. Risk factors, neuroanatomical correlates, and outcome of neuropsychiatric symptoms in Alzheimer’s Disease. J Alzheimers Dis. 2017;60(2):483–493. PubMed CrossRef
Ismail Z, Smith EE, Geda Y, et al; ISTAART Neuropsychiatric Symptoms Professional Interest Area. Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimers Dement. 2016;12(2):195–202. PubMed CrossRef
Gill S, Mouches P, Hu S, et al; Alzheimer’s Disease Neuroimaging Initiative. Using machine learning to predict dementia from neuropsychiatric symptom and neuroimaging data. J Alzheimers Dis. 2020;75(1):277–288. PubMed CrossRef
Ismail Z, McGirr A, Gill S, et al. Mild behavioral impairment and subjective cognitive decline predict cognitive and functional decline. J Alzheimers Dis. 2021;80(1):459–469. PubMed CrossRef
Mortby ME, Ismail Z, Anstey KJ. Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults. Int Psychogeriatr. 2018;30(2):221–232. PubMed CrossRef
Pan Y, Shea YF, Li S, et al. Prevalence of mild behavioural impairment: a systematic review and meta-analysis. Psychogeriatrics. 2021;21(1):100–111. PubMed
Rouse HJ, Small BJ, Schinka JA, et al. Mild behavioral impairment as a predictor of cognitive functioning in older adults. Int Psychogeriatr. 2021;33;(3)285–293. PubMed
Creese B, Brooker H, Ismail Z, 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. PubMed CrossRef
Matsuoka T, Ismail Z, Narumoto J. Prevalence of mild behavioral impairment and risk of dementia in a psychiatric outpatient clinic. J Alzheimers Dis. 2019;70(2):505–513. PubMed CrossRef
Taragano FE, Allegri RF, Heisecke SL, et al. Risk of conversion to dementia in a mild behavioral impairment group compared to a psychiatric group and to a mild cognitive impairment group. J Alzheimers Dis. 2018;62(1):227–238. PubMed CrossRef
Liew TM. Neuropsychiatric symptoms in cognitively normal older persons, and the association with Alzheimer’s and non-Alzheimer’s dementia. Alzheimers Res Ther. 2020;12(1):35. PubMed CrossRef
Palmer K, Di Iulio F, Varsi AE, et al. Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer’s disease: the role of depression and apathy. J Alzheimers Dis. 2010;20(1):175–183. PubMed CrossRef
Peters ME, Rosenberg PB, Steinberg M, et al; Cache County Investigators. Neuropsychiatric symptoms as risk factors for progression from CIND to dementia: the Cache County Study. Am J Geriatr Psychiatry. 2013;21(11):1116–1124. PubMed CrossRef
Yokoi Y, Takano H, Sakata M, et al. Discrete effect of each mild behavioural impairment category on dementia conversion or cognitive decline in patients with mild cognitive impairment. Psychogeriatrics. 2019;19(6):591–600. PubMed CrossRef
Ismail Z, Agüera-Ortiz L, Brodaty H, et al; NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART). 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. PubMed CrossRef
Hilal S, Ikram MK, Saini M, et al. Prevalence of cognitive impairment in Chinese: epidemiology of dementia in Singapore study. J Neurol Neurosurg Psychiatry. 2013;84(6):686–692. PubMed CrossRef
Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997;48(suppl 6):S10–S16. PubMed CrossRef
Sheikh F, Ismail Z, Mortby ME, et al; PROMPT registry investigators. Prevalence of mild behavioral impairment in mild cognitive impairment and subjective cognitive decline, and its association with caregiver burden. Int Psychogeriatr. 2018;30(2):233–244. PubMed CrossRef
Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry. 1982;140(6):566–572. PubMed CrossRef
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198. PubMed CrossRef
Chew KA, Chong EJY, Chen CLH, et al. Psychometric Properties of the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network Neuropsychological Battery in an Asian older adult sample. J Am Med Dir Assoc. 2020;21(6):879–883.e1. PubMed CrossRef
Xu X, Chan QL, Hilal S, et al. The diagnostic utility of the NINDS-CSN neuropsychological battery in memory clinics. Dement Geriatr Cogn Disord Extra. 2016;6(2):276–282. PubMed CrossRef
Chai YL, Yeo HK, Wang J, et al. Apolipoprotein ɛ4 is associated with dementia and cognitive impairment predominantly due to Alzheimer’s Disease and not with vascular cognitive impairment: a Singapore-based cohort. J Alzheimers Dis. 2016;51(4):1111–1118. PubMed CrossRef
Narasimhalu K, Ang S, De Silva DA, et al. The prognostic effects of poststroke cognitive impairment no dementia and domain-specific cognitive impairments in nondisabled ischemic stroke patients. Stroke. 2011;42(4):883–888. PubMed CrossRef
Tan CH, Hilal S, Xu X, et al. MRI markers of mixed pathology and cognitive impairment in Multiethnic Asians. J Alzheimers Dis. 2020;73(4):1501–1509. PubMed CrossRef
Twisk J, de Vente W. Attrition in longitudinal studies: how to deal with missing data. J Clin Epidemiol. 2002;55(4):329–337. PubMed CrossRef
Sanderlin AH, Todem D, Bozoki AC. Obesity and co-morbid conditions are associated with specific neuropsychiatric symptoms in mild cognitive impairment. Front Aging Neurosci. 2017;9:164. PubMed CrossRef
Shi Q, Zhou F, Mei J, et al. The effect of type 2 diabetes mellitus on neuropsychological symptoms in Chinese early Alzheimer’s disease population. Neuropsychiatr Dis Treat. 2020;16:829–836. PubMed CrossRef
Pang FC, Chow TW, Cummings JL, et al. Effect of neuropsychiatric symptoms of Alzheimer’s disease on Chinese and American caregivers. Int J Geriatr Psychiatry. 2002;17(1):29–34. PubMed CrossRef
Roberto N, Portella MJ, Marquié M, et al. Neuropsychiatric profiles and conversion to dementia in mild cognitive impairment, a latent class analysis. Sci Rep. 2021;11(1):6448. PubMed CrossRef
Gill S, Wang M, Mouches P, et al; Alzheimer’s Disease Neuroimaging Initiative. Neural correlates of the impulse dyscontrol domain of mild behavioral impairment. Int J Geriatr Psychiatry. 2021;36(9):1398–1406. PubMed CrossRef
Hayden KM, Reed BR, Manly JJ, et al. Cognitive decline in the elderly: an analysis of population heterogeneity. Age Ageing. 2011;40(6):684–689. PubMed CrossRef
Lussier FZ, Pascoal TA, Chamoun M, et al. Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals. Alzheimers Dement. 2020;16(1):192–199. PubMed CrossRef
Miao R, Chen H-Y, Gill S, et al. Plasma β-amyloid in mild behavioural impairment—neuropsychiatric symptoms on the Alzheimer’s continuum. medRxiv. 2021:2021.2001.2009.21249145.
Johansson M, Stomrud E, Insel PS, et al. Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease. Transl Psychiatry. 2021;11(1):76. PubMed CrossRef
Naude JP, Gill S, Hu S, et al; Alzheimer’s Disease Neuroimaging Initiative. Plasma neurofilament light: a marker of neurodegeneration in mild behavioral impairment. J Alzheimers Dis. 2020;76(3):1017–1027. PubMed CrossRef
Matuskova V, Ismail Z, Nikolai T, et al. Mild behavioral impairment is associated with atrophy of entorhinal cortex and hippocampus in a memory clinic cohort. Front Aging Neurosci. 2021;13:643271. PubMed CrossRef
Kan CN, Gyanwali B, Hilal S, et al. Neuropsychiatric correlates of small vessel disease progression in incident cognitive decline: independent and interactive effects. J Alzheimers Dis. 2020;73(3):1053–1062. PubMed CrossRef