Long-Term Cognitive Decline After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Poststroke cognitive impairment is common, but the trajectory and magnitude of cognitive decline after stroke is unclear. We examined the course and determinants of cognitive change after stroke using individual participant data from the Stroke and Cognition Consortium. METHODS: Nine longitudinal hospital-based cohorts from 7 countries were included. Neuropsychological test scores and normative data were used to calculate standardized scores for global cognition and 5 cognitive domains. One-step individual participant data meta-analysis was used to examine the rate of change in cognitive function and risk factors for cognitive decline after stroke. Stroke-free controls were included to examine rate differences. Based on the literature and our own data that showed short-term improvement in cognitive function after stroke, key analyses were restricted to the period beginning 1-year poststroke to focus on its long-term effects. RESULTS: A total of 1488 patients (mean age, 66.3 years; SD, 11.1; 98% ischemic stroke) were followed for a median of 2.68 years (25th-75th percentile: 1.21-4.14 years). After an initial period of improvement through up to 1-year poststroke, decline was seen in global cognition and all domains except executive function after adjusting for age, sex, education, vascular risk factors, and stroke characteristics (-0.053 SD/year [95% CI, -0.073 to -0.033]; P<0.001 for global cognition). Recurrent stroke and older age were associated with faster decline. Decline was significantly faster in patients with stroke compared with controls (difference=-0.078 SD/year [95% CI, -0.11 to -0.045]; P<0.001 for global cognition in a subgroup analysis). CONCLUSIONS: Patients with stroke experience cognitive decline that is faster than that of stroke-free controls from 1 to 3 years after onset. An increased rate of decline is associated with older age and recurrent stroke.

Vision, vision-specific functioning and mobility, and their relationship with clinically assessed cognitive impairment.

BACKGROUND: The relationship between self-reported visual disability and cognitive impairment in older individuals is unclear. OBJECTIVE: To determine the relationship of vision-specific functioning (VSF), vision-specific mobility (VSM) and visual acuity (VA) with clinically assessed cognitive impairment in the Epidemiology of Dementia in Singapore study. DESIGN: Cross-sectional. SETTING: Population-based. SUBJECTS: Eight hundred and seventy-four adults aged ≥60 years at higher risk of possible cognitive impairment by the Abbreviated Mental Test and progressive forgetfulness question. METHODS: VSF and VSM were measured using Rasch-transformed continuous scores of two Impact of Vision Impairment questionnaire domains. Cognitive impairment was objectively determined using detailed neuropsychological testing and defined as no cognitive impairment (NCI), mild cognitive impairment-no dementia (CIND), moderate CIND only and moderate CIND or dementia. Associations were assessed using multinomial logistic regression models. RESULTS: Of the 874 participants (49.0% males, mean age (SD) 65.5 (7.0) years), 277, 281 and 316 had NCI, mild CIND and moderate CIND or dementia, respectively. Compared to NCI, the odds of moderate CIND, and moderate CIND or dementia increased for every SD worsening in VSF (OR: 1.44, 95% CI 1.14-1.82, and OR: 1.52, 95%CI 1.19-1.94, respectively) and VSM (OR: 1.42, 95%CI 1.11-1.81, and OR: 1.50, 95%CI 1.15-1.95). Similarly, the odds of mild CIND (OR: 1.62, 95%CI 1.19-2.22), moderate CIND (OR: 1.93, 95%CI 1.45-2.58), and moderate CIND or dementia (OR: 2.25, 95%CI 1.62-3.11) increased significantly with every SD worsening of VA. CONCLUSIONS: Our results emphasise the importance of interventions to prevent vision loss and improve quality of life to reduce likelihood of age-related cognitive decline.

Longitudinal trajectory of Amyloid-related hippocampal subfield atrophy in nondemented elderly.

Hippocampal atrophy and abnormal ß-Amyloid (Aß) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aß-associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aß correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET-Aß in AD-vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto-segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aß-related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aß correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal-to-widespread trajectory of Aß-associated hippocampal subfield atrophy over disease progression in nondemented elderly.

Short-term Trajectories of Poststroke Cognitive Function: A STROKOG Collaboration Study.

BACKGROUND AND OBJECTIVES: Past studies on poststroke cognitive function have focused on the average performance or change over time, but few have investigated patterns of cognitive trajectories after stroke. This project used latent class growth analysis (LCGA) to identify clusters of patients with similar patterns of cognition scores over the first-year poststroke and the extent to which long-term cognitive outcome is predicted by the clusters ("trajectory groups"). METHODS: Data were sought from the Stroke and Cognition consortium. LCGA was used to identify clusters of trajectories based on standardized global cognition scores at baseline (T1) and at the 1-year follow-up (T2). One-step individual participant data meta-analysis was used to examine risk factors for trajectory groups and association of trajectory groups with cognition at the long-term follow-up (T3). RESULTS: Nine hospital-based stroke cohorts with 1,149 patients (63% male; mean age 66.4 years [SD 11.0]) were included. The median time assessed at T1 was 3.6 months poststroke, 1.0 year at T2, and 3.2 years at T3. LCGA identified 3 trajectory groups, which were characterized by different mean levels of cognition scores at T1 (low-performance, -3.27 SD [0.94], 17%; medium-performance, -1.23 SD [0.68], 48%; and high-performance, 0.71 SD [0.77], 35%). There was significant improvement in cognition for the high-performance group (0.22 SD per year, 95% CI 0.07-0.36), but changes for the low-performance and medium-performance groups were not significant (-0.10 SD per year, 95% CI -0.33 to 0.13; 0.11 SD per year, 95% CI -0.08 to 0.24, respectively). Factors associated with the low- (vs high-) performance group include age (relative risk ratio [RRR] 1.18, 95% CI 1.14-1.23), years of education (RRR 0.61, 95% CI 0.56-0.67), diabetes (RRR 3.78, 95% CI 2.08-6.88), large artery vs small vessel strokes (RRR 2.77, 95% CI 1.32-5.83), and moderate/severe strokes (RRR 3.17, 95% CI 1.42-7.08). Trajectory groups were predictive of global cognition at T3, but its predictive power was comparable with scores at T1. DISCUSSION: The trajectory of cognitive function over the first-year poststroke is heterogenous. Baseline cognitive function ∼3.6 months poststroke is a good predictor of long-term cognitive outcome. Older age, lower levels of education, diabetes, large artery strokes, and greater stroke severity are risk factors for lower cognitive performance over the first year.

Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study.

BACKGROUND: Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs), and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive decline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. METHODS: We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. RESULTS: Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed similar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. CONCLUSION: Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

Psychometric Properties of the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network Neuropsychological Battery in an Asian Older Adult Sample.

OBJECTIVE: Despite the wide usage of the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) neuropsychological battery for the detection of vascular cognitive impairment, its reliability and validity have not been established. Therefore, the present study established the psychometric properties of the battery in cognitively normal older adults in a clinical setting in Singapore. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: A total of 105 cognitively normal older adults age 50 years and older were assessed in a memory clinic setting. METHODS: The 60-minute NINDS-CSN and 5-minute protocol were administered to participants at baseline and 3-month follow-up. Raw scores were transformed into standardized z scores. Test-retest reliability, concurrent validity and construct (convergent and discriminant) validity were reported. RESULTS: Moderate-to-excellent test-retest reliability (r = 0.36-0.87), concurrent validity, and construct validity (r = 0.41-0.83) were found in both protocols over 3 months (all Ps < 0.01). Although the 5-minute protocol showed moderate validity (r = 0.41), the 60-minute protocol had excellent concurrent validity against a locally validated neuropsychological battery (r = 0.83). CONCLUSION AND IMPLICATIONS: The NINDS-CSN is reliable and valid in assessing cognitive function. The 60-minute protocol demonstrates great utility beyond its current usage in vascular cognitive impairment populations to the general older adult population. The 5-minute protocol can be used as a brief cognitive screening tool in primary healthcare and the community, due to its brevity and accuracy. Future research should further examine the generalizability of the NINDS-CSN battery in other dementias and cognitive disorders.

Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups.

OBJECTIVE: To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. METHODS: We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. RESULTS: In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. CONCLUSIONS: This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.