The prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis

doi:10.1016/j.jad.2015.09.069

Journal of Affective Disorders

Volume 190, 15 January 2016, Pages 264-271

https://doi.org/10.1016/j.jad.2015.09.069 Get rights and content

Highlights

•NPS were highly prevalent in Patients with AD.
•The most frequent NPS was apathy, followed by depression and aggression.
•Disease duration, age and education level can affect the prevalence of NPS.

Abstract

Background

Neuropsychiatric symptoms (NPS) are being increasingly recognized as common serious problems in Alzheimer’s disease (AD). However, published data on the prevalence of NPS in persons with AD are conflicting. This meta-analysis aimed to estimate the prevalence of NPS in persons with AD.

Methods

Studies published from 1964 to September 30, 2014, were identified from PubMed and Embase database, reference lists and conference abstracts. We calculated prevalence rates and conducted meta-regression analysis with random-effects model, according to study characteristics, population demographics or condition information.

Results

We identified 48 eligible articles, which provided data for 12 NPS reported in Neuropsychiatric Inventory (NPI). The most frequent NPS was apathy, with an overall prevalence of 49% (95% CI 41–57%), followed by depression, aggression, anxiety and sleep disorder, the pooled prevalence estimates of which were 42% (95% CI 37–46%), 40% (95% CI 33–46%), 39% (95% CI 32–46%) and 39% (95% CI 30–47%), respectively. The less prevalent NPS were irritability (36%, 31–41%), appetite disorder (34%, 27–41%), aberrant motor behavior (32%, 25–38%), delusion (31%, 27–35%), disinhibition (17%, 12–21%) and hallucination (16%, 13–18%). Least common was euphoria, with an overall prevalence of 7% (95% CI 5–9%).

Limitations

Several aspects, such as the quality of included studies were not always optimal and there was significant heterogeneity of prevalence estimate across studies.

Conclusions

NPS were observed to be highly prevalent in AD patients. Disease duration, age, education level, population origin and the severity of cognitive impairment had influence on the prevalence of some NPS.

Introduction

Neuropsychiatric symptoms (NPS) are being increasingly recognized as core features of Alzheimer's disease (AD) and related dementias (Petrovic et al., 2007). In this article, we choose 12 neuropsychiatric symptoms reported in Neuropsychiatric Inventory (NPI) to study. It was demonstrated that NPS could be identified as different neuropsychiatric sub-syndromes in diverse studies (Aalten et al., 2007, Cheng et al., 2012). Aalten and colleagues reported the largest European database (EADC), identifying four different NPS sub-syndromes: hyperactivity (aggression, disinhibition, irritability, aberrant motor behavior and euphoria), psychosis (delusion, hallucination and sleep disorder), affective (depression and anxiety,) and apathy (apathy and appetite disorder) (Aalten et al., 2007). More than 80% demented patients exhibit at least one neuropsychiatric symptom, since the onset of cognitive impairment (Lyketsos et al., 2002). However, they are often under-recognized and improperly managed in persons with AD (Chow et al., 2002).

The occurrence of NPS in AD can accelerate disease progression and early institutionalization, and interfere with treatment effects and prognosis (Lyketsos et al., 2002, Steffens et al., 2005). Therefore, early and precise recognition of NPS in AD has become urgent as it can be effectively prevented and intervened (Wang et al., 2015). In addition, reliable data on the prevalence of NPS is essential to inform patients and caregivers, ascertain the overall burden of AD, and explore underlying mechanism. Published data on the prevalence rates of NPS in AD patients varied widely. These conflicting results may be attributed to heterogeneity in the study setting, population demographics, evaluation methods or the severity of cognitive impairment (Fuh, 2006, Mega et al., 1996, Teri et al., 1988). A systematic review and meta-analysis could help explain the variability in the existing literature and through pooling, produce more precise estimates of NPS prevalence in AD. The purpose of this systematic review was to investigate the prevalence of NPS in AD.

Section snippets

Search strategy

We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) criteria for systematic review and meta-analysis (Stroup et al., 2000). The search was executed in PubMed (1964–2014) and Embase (1981–2014) database, and references were exported and managed using EndNote X6. The key words used were: delusion OR hallucination OR apathy OR indifference OR depression OR aggression OR agitation OR anxiety OR euphoria OR elation OR disinhibition OR irritability OR aberrant motor

Identification and description of studies

The literature search yielded a total of 20,424 citations: 13,388 from Embase and 7,036 from PubMed (a total of 16,384 after duplicates removed) (Fig. 1). After the initial screen, 412 studies met the criteria for full-text review, of which 370 were excluded (129 not original research, 85 not AD population, 96 no prevalence or sufficient information to calculate an estimate, 24 no eligible NPS assessment methods, 17 sample size<50, 19 from same data sources). Additional 6 articles were included

Discussion

This is the first systematic review and meta-analysis designed to assess the prevalence estimates of neuropsychiatric symptoms in persons with AD, which revealed NPS were highly prevalent in AD (Fig. 5). Though the prevalence of NPS varied widely across studies, the most frequent disturbance reported in AD sample was apathy, followed by depression, aggression, anxiety and sleep disorder, while the least common was euphoria. According to meta-regression analyses, age could affect the prevalence

Author disclosures

The authors have nothing to disclose.

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Research reportThe prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis

Highlights

Abstract

Background

Methods

Results

Limitations

Conclusions

Introduction

Section snippets

Search strategy

Identification and description of studies

Discussion

Author disclosures

J. Formos. Med. Assoc. Taiwan yi zhi

Am. J. Geriatr. Psychiatry: Off. J. Am. Assoc. Geriatr. Psychiatry

Am. J. Geriatr. Psychiatry: Off. J. Am. Assoc. Geriatr. Psychiatry

Sleep. Med.

Am. J. Geriatr. Psychiatry: Off. J. Am. Assoc. Geriatr. Psychiatry

Arch. Gerontol. Geriatr.

J. Psychosom. Res.

Neuropsychiatric syndromes in dementia. Results from the European Alzheimer Disease consortium: part I

Dement. Geriatr. Cogn. Disord.

Delusions and hallucinations in Alzheimer’s disease: prevalence and clinical correlates

Int. J. Geriatr. Psychiatry

Delusions in Alzheimer’s disease and multi-infarct dementia

Acta Neurol. Scand.

Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content

Br. J. Psychiatry: J. Ment. Sci.

Psychiatric phenomena in Alzheimer’s disease. II: Disorders of perception

Br. J. Psychiatry: J. Ment. Sci.

Psychiatric phenomena in Alzheimer’s disease. III: Disorders of mood

Br. J. Psychiatry: J. Ment. Sci.

Psychiatric phenomena in Alzheimer’s disease. IV: Disorders of behaviour

Br. J. Psychiatry: J. Ment. Sci.

Prevalence of neuropsychiatric symptoms in Alzheimer’s disease: a cross-sectional descriptive study in Thailand

J. Med. Assoc. Thail. Chotmaihet Yhangphaet

Neuropsychiatric symptom clusters of Alzheimer’s disease in Hong Kong Chinese: prevalence and confirmatory factor analysis of the Neuropsychiatric Inventory

Int. Psychogeriatrics/IPA

Depression in Taiwanese patients with Alzheimer’s disease determined by the National Institutes of Mental Health Provisional Criteria

Int. Psychogeriatrics/IPA

Neuropsychiatric symptoms of Alzheimer’s disease differ in Chinese and American patients

Int. J. Geriatr. Psychiatry

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J. Gerontol.

Neuropsychiatric symptoms and functional status in Alzheimer’s disease and vascular dementia patients

Curr. Alzheimer Res.

The Columbia University scale for psychopathology in Alzheimer’s disease

Arch. Neurol.

Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer’s disease and mild cognitive impairment subtypes

Int. Psychogeriatrics/IPA

Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis

Biometrics

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BMJ (Clinical Research ed.)

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BMC Neurol.

Prevalence of neuropsychiatric symptoms in elderly patients with dementia in Mungialde County (Basque Country, Spain)

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Research report
The prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis