Diagnosis in vascular dementia, applying ‘Cochrane diagnosis rules’ to ‘dementia diagnostic tools’

In this issue of Clinical Science, Biesbroek and colleagues describe recent work on magnetic resonance imaging (MRI)-based cerebral lesion location and its association with cognitive decline. The authors conclude that diagnostic neuroimaging in dementia should shift from whole-brain evaluation to focused quantitative analysis of strategic brain areas. This commentary uses the review of lesion location mapping to discuss broader issues around studies of dementia test strategies. We draw upon work completed by the Cochrane Dementia and Cognitive Improvement Group designed to improve design, conduct and reporting of dementia biomarker studies

Cochrane dementia group turns 21—older and (slightly) wiser

This invited editorial describes the achievements of the last 21 years of the Cochrane Dementia and Cognitive Improvement Group (DR Quinn is the coordinating editor of the group)

Antidepressants for treating depression in dementia

BackgroundThe use of antidepressants in dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This review updates an earlier version, first published in 2002.ObjectivesTo determine the efficacy and safety of any type of antidepressant for patients who have been diagnosed as having dementia of any type and depression as defined by recognised criteria.Search methodsWe searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register, on 16 August 2017. ALOIS contains information on trials retrieved from databases and from a number of trial registers and grey literature sources.Selection criteriaWe included all relevant double‐blind, randomised trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression.Data collection and analysisTwo review authors selected studies for inclusion and extracted data independently. We assessed risk of bias in the included studies using the Cochrane 'Risk of bias' tool. Where clinically appropriate, we pooled data for treatment periods up to three months and from three to nine months. We used GRADE methods to assess the overall quality of the evidence.Main resultsWe included ten studies with a total of 1592 patients. Eight included studies reported sufficiently detailed results to enter into analyses related to antidepressant efficacy. We split one study which included two different antidepressants and therefore had nine groups of patients treated with antidepressants compared with nine groups receiving placebo treatment. Information needed to make 'Risk of bias' judgements was often missing.We found high‐quality evidence of little or no difference in scores on depression symptom rating scales between the antidepressant and placebo treated groups after 6 to 13 weeks (standardised mean difference (SMD) ‐0.10, 95% confidence interval (CI) ‐0.26 to 0.06; 614 participants; 8 studies). There was probably also little or no difference between groups after six to nine months (mean difference (MD) 0.59 point, 95% CI ‐1.12 to 2.3, 357 participants; 2 studies; moderate‐quality evidence). The evidence on response rates at 12 weeks was of low quality, and imprecision in the result meant we were uncertain of any effect of antidepressants (antidepressant: 49.1%, placebo: 37.7%; odds ratio (OR) 1.71, 95% CI 0.80 to 3.67; 116 participants; 3 studies). However, the remission rate was probably higher in the antidepressant group than the placebo group (antidepressant: 40%, placebo: 21.7%; OR 2.57, 95% CI 1.44 to 4.59; 240 participants; 4 studies; moderate‐quality evidence). The largest of these studies continued for another 12 weeks, but because of imprecision of the result we could not be sure of any effect of antidepressants on remission rates after 24 weeks. There was evidence of no effect of antidepressants on performance of activities of daily living at weeks 6 to 13 (SMD ‐0.05, 95% CI ‐0.36 to 0.25; 173 participants; 4 studies; high‐quality evidence) and probably also little or no effect on cognition (MD 0.33 point on the Mini‐Mental State Examination, 95% CI ‐1.31 to 1.96; 194 participants; 6 studies; moderate‐quality evidence).Participants on antidepressants were probably more likely to drop out of treatment than those on placebo over 6 to 13 weeks (OR 1.51, 95% CI 1.07 to 2.14; 836 participants; 9 studies). The meta‐analysis of the number of participants suffering at least one adverse event showed a significant difference in favour of placebo (antidepressant: 49.2%, placebo: 38.4%; OR 1.55, 95% CI 1.21 to 1.98, 1073 participants; 3 studies), as did the analyses for participants suffering one event of dry mouth (antidepressant: 19.6%, placebo: 13.3%; OR 1.80, 95% CI 1.23 to 2.63, 1044 participants; 5 studies), and one event of dizziness (antidepressant: 19.2%, placebo: 12.5%; OR 2.00, 95% CI 1.34 to 2.98, 1044 participants; 5 studies). Heterogeneity in the way adverse events were reported in studies presented a major difficulty for meta‐analysis, but there was some evidence that antidepressant treatment causes more adverse effects than placebo treatment does.Authors' conclusionsThe available evidence is of variable quality and does not provide strong support for the efficacy of antidepressants for treating depression in dementia, especially beyond 12 weeks. On the only measure of efficacy for which we had high‐quality evidence (depression rating scale scores), antidepressants showed little or no effect. The evidence on remission rates favoured antidepressants but was of moderate quality, so future research may find a different result. There was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. There is some evidence that antidepressant treatment may cause adverse events

When is Alzheimer’s not dementia—Cochrane commentary on The National Institute on Ageing and Alzheimer’s Association Research Framework for Alzheimer’s Disease

Early 2018 saw the release of new diagnostic guidance on Alzheimer’s disease from the National Institute on Ageing and the Alzheimer’s Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer’s disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term ‘Alzheimer’s disease’; and the potential for a research framework to influence clinical practice

Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome

Peer reviewedPublisher PD

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia

Acknowledgements We would like to thank Dr Kate Wang, Dr Andrew Stafford, Ms Catherine Hofstetter, and Dr Joanna Damen for their helpful peer review comments on this protocol.Peer reviewedPublisher PD

Anticholinergic burden (prognostic factor) for prediction of dementia or cognitive decline in older adults with no known cognitive syndrome (Review)

Funding Information: National Institute on Aging, NIH Grants, and the Branta Foundation Funding Information: We followed best practice in design, conduct, and reporting of our prognosis review as detailed in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). The review was supported by the Cochrane Prognostic Methods Group, partners within the Cochrane Mental Health and Neuroscience Network, and the UK National Institute for Health Research Complex Reviews Support Unit (NIHR CRSU). Funding Information: American Philosophical Society, the National Institute on Aging grants, and by the Illinois Department of Public Health to DAB Funding Information: This protocol was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Dementia and Cognitive Improvement group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health Publisher Copyright: Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.Peer reviewedPublisher PD

Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life

Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia

Background: Medications with anticholinergic properties are commonly prescribed to older adults with a pre‐existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor. Objectives: Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre‐existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation. Search methods: We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science. Selection criteria: We included prospective and retrospective longitudinal cohort and case‐control observational studies, with a minimum of one‐month follow‐up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre‐existing diagnoses of dementia or cognitive impairment. Data collection and analysis: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random‐effects meta‐analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. Main results: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk of greater long‐term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low‐ or very low‐certainty evidence for all outcomes. Authors' conclusions: There is low‐certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation

Aducanumab and the certainty of evidence

No abstract available