Zhaolu Wang

Risk factors for incident dementia after stroke and transient ischemic attack

We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA).

Cerebral Microbleeds Is Antithrombotic Therapy Safe to Administer

Growing evidence suggests a link between cerebral microbleeds (CMBs) and increased risk of intracerebral hemorrhage (ICH), leading to concerns on the safety of administering antithrombotic drugs in patients with CMBs. This review summarized studies on the association among CMBs, ICH, and antithrombotic therapy (defined as antiplatelet and anticoagulant agents). Recommendations for future studies on this topic were also proposed. CMBs are small perivascular hemosiderin deposits (usually with macrophages) from leakage through cerebral small vessels, which can be visualized as small, rounded, homogeneous, and hypointense lesions on T2*-weighed gradient-recalled echo or susceptibility-weighted imaging MRI.1 CMBs indicate hemorrhage-prone pathological states, and studies have shown that the presence of CMBs is associated with increased risk of future ICH (odds ratio [OR], 8.52; 95% confidence interval [CI], 4.23–17.18),1 which is also the most feared complication associated with antithrombotic drugs. Thus, it is natural to wonder whether antithrombotic therapy should be averted in patients with CMBs. Different perspectives should be considered to address this question. In this review, we will seek to clarify this topic by answering the following questions: (1) What is the pathophysiology of CMBs? (2) Are CMBs common in populations who might require antithrombotic therapy? (3) Do patients taking antithrombotic therapy develop more CMBs? (4) Under antithrombotic therapy, do patients with CMBs have an increased risk of future ICH compared with patients without CMBs? (5) Does the increased risk of ICH outweigh the benefit of antithrombotic therapy in patients with CMBs? ### What Is the Pathophysiology of CMBs? Figure 1 illustrates our current understanding on the pathophysiology of CMBs. At least 2 pathological mechanisms may lead to CMBs: cerebral amyloid angiopathy (CAA) and hypertensive microangiopathy. CAA, characterized by amyloid-β deposition in vessel walls, is related to apolipoprotein E genotype.2 Amyloid-β, especially inflammatory amyloid, induces local inflammation ranging from mild changes to a granulomatous angiitis with apoptosis …

Influence of Amyloid-β on Cognitive Decline After Stroke/Transient Ischemic Attack Three-Year Longitudinal Study

Background and Purpose— We hypothesized that comorbid amyloid-beta (A&bgr;) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack. Methods— We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11-labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer’s disease. Those with and without Alzheimer’s disease–like A&bgr; deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education. Results— Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group×time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to A&bgr; deposition. Conclusions— Compared with subjects without Alzheimer’s disease–like A&bgr; deposition, those with A&bgr; deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. A&bgr; was associated with changes in multiple cognitive domains.

Montreal Cognitive Assessment: One Cutoff Never Fits All.

Background and Purpose— The objective of this study is to examine the discrepancy between single versus age and education corrected cutoff scores in classifying performance on the Montreal Cognitive Assessment (MoCA) in patients with stroke or transient ischemic attack. Methods— MoCA norms were collected from 794 functionally independent and stroke- and dementia-free persons aged ≥65 years. magnetic resonance imaging was used to exclude healthy controls with significant brain pathology and medial temporal lobe atrophy. Cutoff scores at 16th, 7th, and 2nd percentiles by age and education were derived for the MoCA and MoCA 5-minute Protocol. MoCA performance in 919 patients with stroke or transient ischemic attack was classified using the single and norm-derived cutoff scores. Results— The norms for the Hong Kong version of the MoCA total and domain scores and the total score of the MoCA 5-minute protocol are described. Only 65.1% and 25.7% healthy controls and 45.2% and 19.0% patients scored above the conventional cutoff scores of 21/22 and 25/26 on the MoCA. Using classification with norm-derived cutoff scores as reference, locally derived cutoff score of 21/22 yielded a classification discrepancy of ⩽42.4%. Discrepancy increased with higher age and lower education level, with the majority being false positives by single cutoffs. With the 25/26 cutoff of the original MoCA, discrepancy further increased to ⩽74.3%. Conclusions— Conventional single cutoff scores are associated with substantially high rates of misclassification especially in older and less-educated patients with stroke. These results caution against the use of one-size-fits-all cutoffs on the MoCA.

Risk Factors and Cognitive Relevance of Cortical Cerebral Microinfarcts in Patients With Ischemic Stroke or Transient Ischemic Attack

Background and Purpose— It was recently demonstrated that cerebral microinfarcts (CMIs) can be detected in vivo using 3.0 tesla (T) magnetic resonance imaging. We investigated the prevalence, risk factors, and the longitudinal cognitive consequence of cortical CMIs on 3.0T magnetic resonance imaging, in patients with ischemic stroke or transient ischemic attack. Methods— A total of 231 patients undergoing 3.0T magnetic resonance imaging were included. Montreal Cognitive Assessment was used to evaluate global cognitive functions and cognitive domains (memory, language, and attention visuospatial and executive functions). Cognitive changes were represented by the difference in Montreal Cognitive Assessment score between baseline and 28-month after stroke/transient ischemic attack. The cross-sectional and longitudinal associations between cortical CMIs and cognitive functions were explored using ANCOVA and regression models. Results— Cortical CMIs were observed in 34 patients (14.7%), including 13 patients with acute (hyperintense on diffusion-weighted imaging) and 21 with chronic CMIs (isointense on diffusion-weighted imaging). Atrial fibrillation was a risk factor for all cortical CMIs (odds ratio, 4.8; 95% confidence interval, 1.5–14.9; P=0.007). Confluent white matter hyperintensities was associated with chronic CMIs (odds ratio, 2.8; 95% confidence interval, 1.0–7.8; P=0.047). The presence of cortical CMIs at baseline was associated with worse visuospatial functions at baseline and decline over 28-month follow-up (&bgr;=0.5; 95% confidence interval, 0.1–1.0; P=0.008, adjusting for brain atrophy, white matter hyperintensities, lacunes, and microbleeds). Conclusions— Cortical CMIs are a common finding in patients with stroke/transient ischemic attack. Associations between CMI with atrial fibrillation and white matter hyperintensities suggest that these lesions have a heterogeneous cause, involving microembolism and cerebral small vessel disease. CMI seemed to preferentially impact visuospatial functions as assessed by a cognitive screening test.

Delayed-onset dementia after stroke or transient ischemic attack

Patients surviving stroke without immediate dementia are at high risk of delayed‐onset dementia. Mechanisms underlying delayed‐onset dementia are complex and may involve vascular and/or neurodegenerative diseases.

Pulse Pressure and Cognitive Decline in Stroke Patients With White Matter Changes

The authors hypothesized that both high and low pulse pressure (PP) may predict cognitive decline in stroke/transient ischemic attack (TIA) patients with white matter changes (WMCs). The authors prospectively followed up 406 ischemic stroke/TIA patients with confluent WMCs over 18 months. PP was measured at 3 to 6 months after stroke/TIA and categorized into four groups by quartile. Cognition was assessed 3 to 6 months and 15 to 18 months after stroke/TIA using the Clinical Dementia Rating and Mini‐Mental State Examination (MMSE). Logistic regression showed that patients in the first quartile of PP had a 5.9‐fold higher risk for developing cognitive decline than patients in the third quartile (odds ratio, 5.9; 95% confidence interval, 1.7–20.6), while patients in the fourth quartile had a 3.5‐fold higher risk for cognitive decline than those in the third quartile (odds ratio, 3.5; 95% confidence interval, 1.0–12.4). This U‐shaped relationship was also evident between PP and cognitive decline in MMSE, underlining the role of arterial stiffness and hypoperfusion in cognitive decline related to small vessel disease.

Neuropsychiatric Symptom Clusters in Stroke and Transient Ischemic Attack by Cognitive Status and Stroke Subtype: Frequency and Relationships with Vascular Lesions, Brain Atrophy and Amyloid.

Background The objectives of this study are 1) to examine the frequencies of neuropsychiatric symptom clusters in patients with stroke or transient ischemic attack (TIA) by cognitive level and stroke subtype; and 2) to evaluate effect of demographic, clinical, and neuroimaging measures of chronic brain changes and amyloid upon neuropsychiatric symptom clusters. Methods Hospital-based, cross-sectional study. 518 patients were administered the Neuropsychiatric Inventory (NPI) 3–6 months post index admission. NPI symptoms were classified into four symptom clusters (Behavioral Problems, Psychosis, Mood Disturbance & Euphoria) derived from a confirmatory factor analysis of the 12 NPI items. Multivariable logistic regression was used to determine independent associations between demographic, clinical and neuroimaging measures of chronic brain changes (white matter changes, old infarcts, whole brain atrophy, medial temporal lobe atrophy [MTLA] and frontal lobe atrophy [FLA]) with the presence of NPI symptoms and all symptom clusters except euphoria. 11C-Pittsburg Compound B Positron Emission Tomography (11C-PiB PET) was performed in 24 patients to measure amyloid retention for Alzheimer’s Disease (AD) pathology. Results 50.6% of the whole sample, including 28.7% cognitively normal and 66.7% of patients with mild cognitive symptoms, had ≥1 NPI symptoms. Frequencies of symptom clusters were largely similar between stroke subtypes. Compared to patients with cardioembolic stroke and intracranial haemorrhage, those with TIA had less frequent mood disturbance. Stroke severity at admission and MTLA were the most robust correlates of symptoms. FLA was associated with behavioral problems cluster only. Frequency of symptom clusters did not differ between patients with and without significant amyloid retention. Conclusion Frequency of neuropsychiatric symptoms increased with level of cognitive impairment but was largely similar between stroke subtypes. Stroke severity and MTLA were associated with neuropsychiatric symptoms. AD pathology appeared to be unrelated to neuropsychiatric manifestations but further studies with larger sample size are required to substantiate this finding.

Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients

Background: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). Methods: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. Results: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). Conclusion: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

Relations between Recent Past Leisure Activities with Risks of Dementia and Cognitive Functions after Stroke

Background Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. Methods Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3–6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3–6 months after stroke. Results Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20–0.63) and stretching & toning physical exercise (0.37, 0.21–0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. Conclusions Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive performance. Findings of this retrospective cohort study call for studies of activity intervention for prevention of cognitive decline in individuals at elevated risk of stroke.