Neuropsychiatric symptoms associated with cerebral small vessel disease: a systematic review and meta-analysis. 2021

Una Clancy, and Daniel Gilmartin, and Angela C C Jochems, and Lucy Knox, and Fergus N Doubal, and Joanna M Wardlaw
Centre for Clinical Brain Sciences and UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.

Cerebral small vessel disease, a common cause of vascular dementia, is often considered clinically silent before dementia or stroke become apparent. However, some individuals have subtle symptoms associated with acute MRI lesions. We aimed to determine whether neuropsychiatric and cognitive symptoms vary according to small vessel disease burden. In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and PsycINFO for articles published in any language from database inception to Jan 24, 2020. We searched for studies assessing anxiety, apathy, delirium, emotional lability, fatigue, personality change, psychosis, dementia-related behavioural symptoms or cognitive symptoms (including subjective memory complaints), and radiological features of cerebral small vessel disease. We extracted reported odds ratios (OR), standardised mean differences (SMD), and correlations, stratified outcomes by disease severity or symptom presence or absence, and pooled data using random-effects meta-analyses, reporting adjusted findings when possible. We assessed the bias on included studies using the Risk of Bias for Non-randomized Studies tool. This study is registered with PROSPERO, CRD42018096673. Of 7119 papers identified, 81 studies including 79 cohorts in total were eligible for inclusion (n=21 730 participants, mean age 69·2 years). Of these 81 studies, 45 (8120 participants) reported effect estimates. We found associations between worse white matter hyperintensity (WMH) severity and apathy (OR 1·41, 95% CI 1·05-1·89) and the adjusted SMD in apathy score between WMH severities was 0·38 (95% CI 0·15-0·61). Worse WMH severity was also associated with delirium (adjusted OR 2·9, 95% CI 1·12-7·55) and fatigue (unadjusted OR 1·63, 95% CI 1·20-2·22). WMHs were not consistently associated with subjective memory complaints (OR 1·34, 95% CI 0·61-2·94) and unadjusted SMD for WMH severity between these groups was 0·08 (95% CI -0·31 to 0·47). Anxiety, dementia-related behaviours, emotional lability, and psychosis were too varied or sparse for meta-analysis; these factors were reviewed narratively. Overall heterogeneity varied from 0% to 79%. Only five studies had a low risk of bias across all domains. Apathy, fatigue, and delirium associated independently with worse WMH, whereas subjective cognitive complaints did not. The association of anxiety, dementia-related behaviours, emotional lability, and psychosis with cerebral small vessel disease require further investigation. These symptoms should be assessed longitudinally to improve early clinical detection of small vessel disease and enable prevention trials to happen early in the disease course, long before cognition declines. Chief Scientist Office of the Scottish Government, UK Dementia Research Institute, Fondation Leducq, Stroke Association Garfield-Weston Foundation, Alzheimer's Society, and National Health Service Research Scotland.

UI MeSH Term Description Entries
D005221 Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Lassitude
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001523 Mental Disorders Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. Mental Illness,Psychiatric Diseases,Psychiatric Disorders,Psychiatric Illness,Behavior Disorders,Diagnosis, Psychiatric,Mental Disorders, Severe,Psychiatric Diagnosis,Illness, Mental,Mental Disorder,Mental Disorder, Severe,Mental Illnesses,Psychiatric Disease,Psychiatric Disorder,Psychiatric Illnesses,Severe Mental Disorder,Severe Mental Disorders
D017281 Cost of Illness The personal cost of disease which may be economic, social, or psychological. The cost of illness may be reflected in absenteeism, productivity, response to treatment, peace of mind, or QUALITY OF LIFE. It differs from HEALTH CARE COSTS, the societal cost of providing services related to the delivery of health care. Burden Of Disease,Burden of Illness,Disease Burden,Disease Costs,Cost of Disease,Cost of Sickness,Costs of Disease,Disease Cost,Economic Burden of Disease,Sickness Cost,Burden Of Diseases,Burden, Disease,Cost, Disease,Disease Burdens,Illness Burden,Illness Burdens,Illness Cost,Illness Costs,Sickness Costs
D059345 Cerebral Small Vessel Diseases Pathological processes or diseases where cerebral MICROVESSELS show abnormalities. They are often associated with aging, hypertension and risk factors for lacunar infarcts (see LACUNAR INFARCTION); LEUKOARAIOSIS; and CEREBRAL HEMORRHAGE. Cerebral Microangiopathies,Cerebral Small Vessel Disease,Cerebral Microangiopathy,Microangiopathies, Cerebral,Microangiopathy, Cerebral

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