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

Clancy, Una; Gilmartin, Daniel; Jochems, Angela C. C.; Knox, Lucy; Doubal, Fergus; Wardlaw, Joanna M.

doi:10.1016/s2215-0366(20)30431-4

Cited by 100 publications

(118 citation statements)

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“…European Stroke Journal 6 (2) lesions are not 'silent' especially when present in larger numbers involving more areas of the brain. In fact patients with higher burdens of ccSVD lesions have atypical neurological, neuropsychiatric and cognitive symptoms (summarised in 10 ) but these are poorly recognised in clinical practice and probably also by patients, and therefore have not received much attention and have not, as yet, been used to identify relevant patients in clinical trials. Furthermore, SVD affects multiple cognitive domains including memory and not just executive function as is commonly thought.…”

Section: CXIImentioning

confidence: 99%

“…Clinical management of ccSVD is hampered by difficulty recognising the atypical neurological, neuropsychiatric symptoms 10 and cognitive profiles 11,12 Wardlaw et al CLI associated with higher burden of ccSVD lesions and likely to differentiate patients with a high risk of progression to clinical outcomes. 5 Better recognition and definition of these symptoms might help identify patients at high risk of adverse SVD outcomes for focused clinical trials.…”

Section: Implications For Future Researchmentioning

confidence: 99%

“…Even though aspirin could be harmful in this situation in older people, other weak antiplatelet drugs which have additional pharmacological effects could be beneficial, such as cilostazol. Furthermore, better recognition and definition of the atypical neuropsychiatric and cognitive symptoms that are associated with ccSVD 10 and other markers currently in investigation may help identify a group of patients for ‘secondary prevention’, with a high burden of disease and higher risk for future ischaemic events and/or a lower risk of bleeding complications, who might benefit from aspirin or equivalent drugs, and could be tested in clinical trials.…”

Section: Rationale For Expert Consensus Statementmentioning

confidence: 99%

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ESO Guideline on covert cerebral small vessel disease

Wardlaw

Debette

Jokinen

et al. 2021

European Stroke Journal

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‘Covert’ cerebral small vessel disease (ccSVD) is common on neuroimaging in persons without overt neurological manifestations, and increases the risk of future stroke, cognitive impairment, dependency, and death. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist with clinical decisions about management of ccSVD, specifically white matter hyperintensities and lacunes, to prevent adverse clinical outcomes. The guidelines were developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We prioritised the clinical outcomes of stroke, cognitive decline or dementia, dependency, death, mobility and mood disorders, and interventions of blood pressure lowering, antiplatelet drugs, lipid lowering, lifestyle modifications, glucose lowering and conventional treatments for dementia. We systematically reviewed the literature, assessed the evidence, formulated evidence-based recommendations where feasible, and expert consensus statements. We found little direct evidence, mostly of low quality. We recommend patients with ccSVD and hypertension to have their blood pressure well controlled; lower blood pressure targets may reduce ccSVD progression. We do not recommend antiplatelet drugs such as aspirin in ccSVD. We found little evidence on lipid lowering in ccSVD. Smoking cessation is a health priority. We recommend regular exercise which may benefit cognition, and a healthy diet, good sleep habits, avoiding obesity and stress for general health reasons. In ccSVD, we found no evidence for glucose control in the absence of diabetes or for conventional Alzheimer dementia treatments. Randomised controlled trials with clinical endpoints are a priority for ccSVD.

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Section: CXIImentioning

confidence: 99%

Section: Implications For Future Researchmentioning

confidence: 99%

Section: Rationale For Expert Consensus Statementmentioning

confidence: 99%

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ESO Guideline on covert cerebral small vessel disease

Wardlaw

Debette

Jokinen

et al. 2021

European Stroke Journal

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“…Behavioral and psychological symptoms are highly frequent among cerebrovascular disease manifestations 11,12 and might be different according to the nature of cerebrovascular lesions. 13 Those symptoms might be undervalued by relatives (and interpreted for instance as due to ageing) or overlooked due to other concomitant cognitive symptoms.…”

Section: Resultsmentioning

confidence: 99%

“…One last word concerning subjective CI, that usually is associated with higher risk of dementia, usually of the Alzheimer type (and not with SVD). 12 However, among community cohorts, may represent an increase in the relative risk risk for, particularly, CI of vascular origin. 23 Clinicians should keep in mind that patients with subjective complaints living in the community are an opportunity to identify vascular risk factors in people otherwise well, and reinforce preventive actions concerning those vascular risk factors.…”

Section: Resultsmentioning

confidence: 99%

Cerebrovascular disease in patients with cognitive impairment: A white paper from the ESO dementia committee – A practical point of view with suggestions for the management of cerebrovascular diseases in memory clinics

Verdelho

Biessels

Chabriat

et al. 2021

European Stroke Journal

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Purpose Practical suggestions on clinical decisions about vascular disease management in patients with cognitive impairment are proposed. Methods The document was produced by the Dementia Committee of the European Stroke Organisation (ESO) based on the evidence from the literature where available and on the clinical experience of the Committee members. This paper was endorsed by the ESO. Findings Vascular risk factors and cerebrovascular disease are frequent in patients with cognitive impairment. While acute stroke treatment has evolved substantially in last decades, evidence of management of cerebrovascular pathology beyond stroke in patients with cognitive impairment and dementia is quite limited. Additionally, trials to test some daily-life clinical decisions are likely to be complex, difficult to undertake and take many years to provide sufficient evidence to produce recommendations. This document was conceived to provide some suggestions until data from field trials are available. It was conceived for the use of clinicians from memory clinics or involved specifically in cognitive disorders, addressing practical aspects on diagnostic tools, vascular risk management and suggestions on some therapeutic options. Discussion and conclusions The authors did not aim to do an exhaustive or systematic review or to cover all current evidence. The document approach in a very practical way frequent issues concerning cerebrovascular disease in patients with known cognitive impairment.

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Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study

Low,

McKiernan,

Prats-Sedano

et al. 2024

JAMA Netw Open

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ImportanceTraumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI.ObjectiveTo assess whether TBI are associated with and interact with midlife changes in neuroimaging and clinical features in otherwise healthy individuals.Design, Setting, and ParticipantsThis cross-sectional analysis used baseline data from the PREVENT Dementia program collected across 5 sites in the UK and Ireland between 2014 and 2020. Eligible participants were cognitively healthy midlife adults aged between 40 and 59 years. Data were analyzed between January 2023 and April 2024.ExposureLifetime TBI history was assessed using the Brain Injury Screening Questionnaire.Main Outcomes and MeasuresCerebral microbleeds and other markers of cerebral small vessel disease (white matter hyperintensities [WMH], lacunes, perivascular spaces) were assessed on 3T magnetic resonance imaging. Clinical measures were cognition, sleep, depression, gait, and cardiovascular disease (CVD) risk, assessed using Computerized Assessment of Information Processing (COGNITO), Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies Depression Scale, clinical interviews, and the Framingham Risk Score, respectively.ResultsOf 617 participants (median [IQR] age, 52 [47-56] years; 380 female [61.6%]), 223 (36.1%) had a history of TBI. TBI was associated with higher microbleed count (β = 0.10; 95% CI, 0.01-0.18; P = .03), with a dose-response association observed with increasing number of TBI events (β = 0.05; 95% CI, 0.01-0.09; P = .03). Conversely, TBI was not associated with other measures of small vessel disease, including WMH. Furthermore, TBI moderated microbleed associations with vascular risk factors and clinical outcomes, such that associations were present only in the absence of TBI. Importantly, observations held when analyses were restricted to individuals reporting only mild TBI.Conclusions and RelevanceIn this cross-sectional study of healthy middle-aged adults, detectable changes in brain imaging and clinical features were associated with remote, even mild, TBI in the general population. The potential contribution of vascular injury to TBI-related neurodegeneration presents promising avenues to identify potential targets, with findings highlighting the need to reduce TBI through early intervention and prevention in both clinical care and policymaking.

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

Cited by 100 publications

References 102 publications

ESO Guideline on covert cerebral small vessel disease

ESO Guideline on covert cerebral small vessel disease

Cerebrovascular disease in patients with cognitive impairment: A white paper from the ESO dementia committee – A practical point of view with suggestions for the management of cerebrovascular diseases in memory clinics

Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study

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