Impact of Small Vessel Disease Progression on Long-term Cognitive and Functional Changes after Stroke

Funding Information: This study was supported in part by the Wellcome Trust (WT088134/Z/09/A; funded most of the data collection and S.D.J.M). For the purpose of open access, the author has applied a CC-BY public copyright license to any Author Accepted Manuscript version arising from this submission. The 3-year follow-up was also funded by Chest, Heart Stroke Scotland:Res14/A157 (C.A.M.); support for the research was also received from NHS Research Scotland (V.C., F.D.); Row Fogo Charitable Trust Centre for Research Into Aging and the Brain (BROD.FID3668413; M.d.C.V.H., E.S.); the European Union Horizon 2020 project 666,881, SVDs@Target (F.M.C); Scottish Funding Council, Scottish Imaging Network, A Platform for Scientific Excellence Initiative; Chief Scientist Office Scotland (U.C.; CAF/18/08); Stroke Association Princess Margaret Research Development Fellowship (U.C.); and Stroke Association–Garfield Weston Foundation Senior Clinical Lectureship (FND;TSALECT 2015/04). Funding provided by the Fondation Leducq (16-CVD-05) and UK Dementia Research Institute (J.M.W.), funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK, is gratefully acknowledged.Peer reviewedPublisher PD

Functional, cognitive and physical outcomes 3 years after minor lacunar or cortical ischaemic stroke

Chest, Heart Stroke Scotland, Ref No: Res14/A157; NHS Research Scotland; The Wellcome Trust (WT088134/Z/09/A); the Row Fogo Charitable Trust; the European Union Horizon 2020, PHC-03-15, project No 666881, ’SVDs@ target’; the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease, Ref No: 16 CVD 05; the Medical Research Council through the UK Dementia Research Institute; the Scottish Funding Council through the Scottish Imaging Network, APeer reviewedPublisher PD

Temporal course of cognitive and behavioural changes in motor neuron diseases

Background Cognitive and behavioural dysfunction may occur in people with motor neuron disease (MND), with some studies suggesting an association with the C9ORF72 repeat expansion. Their onset and progression, however, is poorly understood. We explored how cognition and behaviour change over time, and whether demographic, clinical and genetic factors impact these changes. Methods Participants with MND were recruited through the Phenotype-Genotype-Biomarker study. Every 3–6 months, the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was used to assess amyotrophic lateral sclerosis (ALS) specific (executive functioning, verbal fluency, language) and ALS non-specific (memory, visuospatial) functions. Informants reported on behaviour symptoms via semi-structured interview. Results Participants with neuropsychological data at ≥3 visits were included (n=237, mean age=59, 60% male), of which 18 (8%) were C9ORF72 positive. Baseline cognitive impairment was apparent in 18 (8%), typically in ALS specific domains, and associated with lower education, but not C9ORF72 status. Cognition, on average, remained stable over time, with two exceptions: (1) C9ORF72 carriers declined in all ECAS domains, (2) 8%–9% of participants with baseline cognitive impairment further declined, primarily in the ALS non-specific domain, which was associated with less education. Behavioural symptoms were uncommon. Conclusions In this study, cognitive dysfunction was less common than previously reported and remained stable over time for most. However, cognition declines longitudinally in a small subset, which is not entirely related to C9ORF72 status. Our findings raise questions about the timing of cognitive impairment in MND, and whether it arises during early clinically manifest disease or even prior to motor manifestations

Stability of estimated premorbid cognitive ability over time after minor stroke and its relationship with post-stroke cognitive ability

Considering premorbid or “peak” adult intelligence (IQ) is important when examining post-stroke cognition. The stability of estimated premorbid IQ and its relationship to current cognitive ability in stroke is unknown. We investigated changes in estimated premorbid IQ and current cognitive ability up to three years post-stroke. Minor stroke patients (NIHSS < 8) were assessed at one to three months, one and three years’ post-stroke. The National Adult Reading Test (NART) and Addenbrooke’s Cognitive Examination-Revised (ACE-R) were used to estimate premorbid IQ (NART IQ) and current cognitive ability respectively at each time-point. Baseline demographics, vascular and stroke characteristics were included. Of the 264 patients recruited (mean age 66), 158 (60%), 151 (57%), and 153 (58%) completed cognitive testing at each time-point respectively. NART IQ initially increased (mean difference (MD) = 1.32, 95% CI = 0.54 to 2.13, p < 0.001) before decreasing (MD = −4.269, 95% CI = −5.12 to −3.41, p < 0.001). ACE-R scores initially remained stable (MD = 0.29, 95% CI = −0.49 to 1.07, p > 0.05) before decreasing (MD = −1.05, 95% CI = −2.08 to −0.01, p < 0.05). Adjusting for baseline variables did not change the relationship between NART IQ and ACE-R with time. Increases in NART IQ were associated with more education. For ACE-R, older age was associated with declines, and higher NART IQ and more education was associated with increases. Across 3 years, we observed fluctuations in estimated premorbid IQ and minor changes in current cognitive ability. Future research should aim to identify variables associated with these changes. However, studies of post-stroke cognition should account for premorbid IQ

The relation between total cerebral small vessel disease burden and gait impairment in patients with minor stroke

Acknowledgements We thank the patients and their families, and the staff of the Brain Research Imaging Centre, Edinburgh, where MRI scanning was performed. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Mild Stroke Study-2 follow up study at three years was funded by Chest Heart Stroke Scotland. The original MSS-2 study was funded by the Wellcome Trust (ref. 088134/Z/09/A) and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). The work was supported by European Union Horizon 2020 (EU H2020), PHC03-15, project No 666881, ’SVDs@Target’, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref no. 16 CVD 05. The work reflects the views of the authors and not of the funders. CMJL was supported by the Dutch Alzheimer Foundation and VC holds a NHS Research Scotland Fellowship. The work was performed in the Edinburgh Dementia Research Centre in the UK DementiaResearch InitiativePeer reviewedPublisher PD

Sensitivity analysis comparing studies with depression defined as mild symptoms and above vs clinical depression or severe depressive symptoms only.

<p>Sensitivity analysis comparing studies with depression defined as mild symptoms and above vs clinical depression or severe depressive symptoms only.</p

PRISMA flow chart of search process.

<p>PRISMA flow chart of search process.</p

Mean years of education for those with and without post-stroke depression.

<p>Random effects model for the mean difference. Negative mean difference = lower education decreases risk of post-stroke depression and positive mean difference = higher education decreases risk of post-stroke depression.</p