Cerebral small vessel disease may be associated with apathy, fatigue and delirium

Severe cerebral small vessel disease, a common cause of vascular dementia, may be linked to apathy, fatigue and delirium, according to results of a systematic review and meta-analysis published in Lancet Psychiatry.

“Further investigation of subtle symptoms of small vessel disease that extend beyond objective cognitive testing is required because these symptoms could provide preclinical indicators of vascular cognitive decline,” Una Clancy, MBBCh, of the Centre for Clinical Brain Sciences and U.K. Dementia Research Institute at the University of Edinburgh, and colleagues wrote. “Discriminating whether these symptoms are related to causes of, or are consequent to, small vessel disease lesions, requires assessment of associations in both healthy and diseased populations. With the exception of depression, no published meta-analysis has assessed the association between neuropsychiatric symptoms and imaging features of small vessel disease.”

The investigators sought to determine whether neuropsychiatric and cognitive symptoms were influenced by the presence of small vessel disease burden. They searched four databases for articles published in any language between database inception to Jan. 24, 2020, specifically for those that assessed anxiety, apathy, delirium, emotional lability, fatigue, personality change, psychosis, dementia-related behavioral symptoms or cognitive symptoms, as well as radiological features of cerebral small vessel disease. They included 81 studies, with 21,730 participants with a mean age of 69.2 years, and 45 that reported effect estimates, with 8,120 participants.

Results showed links between worse white matter hyperintensity (WMH) severity and apathy (OR = 1.41; 95% CI, 1.05-1.89). The adjusted standardized mean differences in apathy score between WMH severities was 0.38 (95% CI, 0.15-0.61). The researchers reported associations between worse WMH severity and delirium (adjusted OR = 2.9; 95% CI, 1.12-7.55) and fatigue (unadjusted OR = 1.63; 95% CI, 1.2-2.22). However, they did not observe a consistent association between WMHs and subjective memory complaints (OR = 1.34; 95% CI, 0.61-2.94). Unadjusted standardized mean differences for WMH severity between these groups was 0.08 (95% CI, –0.31 to 0.47). Clancy and colleagues narratively reviewed anxiety, dementia-related behaviors, emotional lability and psychosis, since they were too varied or sparse for meta-analysis. They noted a variance in overall heterogeneity of 0% to 79%. A total of five studies had a low risk for bias across all domains.

“More longitudinal imaging studies are needed to determine whether these symptoms associate temporally with development or worsening of small vessel disease lesions according to subtype, location, overall burden and other clinical factors, including preexisting symptoms, clinical presentations, cognition, social and early life factors,” the researchers wrote. “Future multimodal approaches to patient assessment should holistically incorporate both subjective and objective measures to increase prediction of the presence or progression of small vessel disease. Efforts to refine possible behavioral phenotypes of small vessel disease presence and progression would allow researchers to test potential treatments early in the disease course, before dementia or stroke development.”