Risk factors for dementia and cognitive impairment within 5 years after stroke: a prospective multicentre cohort study
Jule Filler, Marios K. Georgakis, Daniel Janowitz, Marco Duering, Rong Fang, Anna Dewenter, Felix J. Bode, Sebastian Stoesser, Christine Kindler, Péter Hermann, Christian H. Nolte, Thomas Liman, Lucia Kerti, Kathleen Bernkopf, Benno Ikenberg, Wenzel Glanz, Michael Wagner, Annika Spottke, Karin Waegemann, Michael Goertler, Silke Wunderlich, Matthias Endres, Inga Zerr, Gabor C. Petzold, Martin Dichgans, Tatjana Wittenberg, Jan F. Scheitz, Harald Prüß, Pia S. Sperber, Alexander H. Nave, Anna Kufner Ibaroule, Julius N. Meißner, Taraneh Ebrahimi, Julia Nordsiek, Niklas M. Beckonert, Matthias Schmitz, Stefan Goebel, Timothy Bunck, Julia Schütte‐Schmidt, Sabine Nuhn, Corinna Volpers, Peter Dechent, Mathias Bähr, Anna Kopczak, Frank A. Wollenweber, Christiane Huber, Holger Poppert, Tony Stöcker, Katja Neumann, Oliver Speck
Abstract
Background: Stroke survivors frequently experience subsequent cognitive impairment or dementia. We aimed to identify risk factors for post-stroke dementia (PSD) and cognitive impairment (PSCI) within 5 years after stroke. Methods: The DEMDAS (German Center for Neurological Diseases (DZNE) mechanisms of dementia after stroke) study is a prospective cohort of stroke patients admitted to six German tertiary stroke centres between May 1, 2011 and January 31, 2019. Eligible dementia-free patients with ischaemic or haemorrhagic stroke underwent baseline examinations and regular clinical, neuropsychological, and neuroimaging follow-ups over 5 years, with the last follow-ups completed in January 2024. PSD was the primary outcome, determined by comprehensive cognitive testing, patient and informant interviews, and review of medical records. The secondary outcomes were early-onset PSD (3-6 months), delayed-onset PSD (>6 months), and PSCI. Associations between baseline risk factors and PSD were assessed using Cox regression models adjusted for age, sex, education, and stroke severity. Findings: Of 736 patients (245 [33%] female, mean age 68·0 years [SD 11·2], median admission National Institutes of Health Stroke Scale (NIHSS) 3 [IQR 1-5]), 557 (76%) were followed up until death or the end of the study, and 706 (96%) contributed to the PSD analysis. During a median of 5·0 years [IQR 3·3-5·1] of follow-up, 55 new dementia cases were diagnosed (6-month incidence: 3·1% [1·8-4·5], 5-year incidence: 8·8% [6·5-11·1]), of which 21 (38%) were classified as early-onset PSD. The 5-year risk of PSD was associated with older age (HR 1·13 [95% CI 1·08-1·18] per year), higher stroke severity (1·08 [1·03-1·13] per point on NIHSS), lower educational attainment (1·16 [1·05-1·28] per year), acute phase cognitive impairment (5·86 [2·21-15·58]), lower Barthel Index (1·10 [1·05-1·16] per 5 points less), atrial fibrillation (1·91 [1·10-3·30]), metabolic syndrome (MetS, 2·05 [1·15-3·64]), particularly reduced high-density lipoprotein cholesterol (HDL-C, 2·61 [1·50-4·52]) and pre-/diabetes mellitus (2·13 [1·13-4·00]), imaging markers of small vessel disease, and stroke recurrence during follow-up (2·36 [1·16-4·83]). Patients who received acute reperfusion treatment had a 65% lower risk of PSD than those who did not (0·35 [0·16-0·77]). While factors related to the severity of the index stroke were more strongly associated with early-onset PSD, MetS showed a stronger association with delayed-onset PSD. The association between MetS and PSD was independent of stroke recurrence and consistent across age subgroups, with 5-year cumulative incidence ranging from 1·7% (0·0-4·0) in patients ≤65 years without MetS to 24·5% (14·3-33·4) in patients ≥74 years with MetS. Interpretation: The risk of dementia after stroke is multifactorial, with differing risk profiles for early-onset and delayed-onset PSD. Metabolic syndrome, including reduced HDL-C, emerged as a novel risk factor and potential target for PSD prevention. Funding: German Center for Neurodegenerative Diseases (DZNE).