2-(4--(methylamino)phenyl)-6-hydroxybenzothiazole and Stroke

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.. Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA.. Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD.. Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Topics: Adult; Aged; Aged, 80 and over; Aniline Compounds; Apolipoproteins E; Brain; Dementia; Female; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Middle Aged; Phenanthrolines; Positron-Emission Tomography; Prospective Studies; Stroke; Thiazoles; Time Factors; Tomography, X-Ray Computed; Young Adult

We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA).. We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia.. Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively.. Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.

Topics: Age Factors; Aged; Aged, 80 and over; Aniline Compounds; Biomarkers; Brain; Chronic Disease; Cohort Studies; Cross-Sectional Studies; Dementia; Diabetes Mellitus; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Neuroimaging; Positron-Emission Tomography; Radiopharmaceuticals; Risk Factors; Severity of Illness Index; Stroke; Temporal Lobe; Thiazoles; White Matter

We hypothesized that comorbid amyloid-beta (Aβ) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack.. 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 Aβ 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.. 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 Aβ deposition.. Compared with subjects without Alzheimer's disease-like Aβ deposition, those with Aβ deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Aβ was associated with changes in multiple cognitive domains.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Carbon Radioisotopes; Cognition Disorders; Female; Follow-Up Studies; Humans; Ischemic Attack, Transient; Longitudinal Studies; Male; Positron-Emission Tomography; Registries; Stroke; Thiazoles; Time Factors

Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aβ deposits, detected by N-methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors.. Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference.. Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68-77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2-0.44; P=0.001) at median 10 (interquartile range, 7-14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (P=0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28-0.72).. PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.

Topics: Aged; Amyloid beta-Peptides; Aniline Compounds; Atrial Fibrillation; Brain Infarction; Carbon Radioisotopes; Case-Control Studies; Diabetes Complications; Female; Humans; Hyperlipidemias; Hypertension; Male; Neocortex; Phenanthrolines; Positron-Emission Tomography; Risk Factors; Smoking; Stroke; Thiazoles

We hypothesize that Pittsburgh compound B (PIB) binding is common in poststroke dementia (PSD) and that cognitive decline may be faster in PIB positive patients. We performed PIB positron emission tomography (PET) among 17 subjects: 10 PSD patients, 4 Alzheimer's disease (AD) patients, and 3 healthy controls. We also compared the rate of change in mini-mental state examination (MMSE) between PIB positive and negative patients. We detected AD-like PIB binding in 4 PSD patients (40%), all the AD patients, and 1 healthy control. The global PIB retention standardized uptake value (SUV) at 35-45 min for PIB positive stroke patients was 1.67 (range 1.56-1.82), which was similar to the AD patients (1.65; range 1.46-1.88) and was lower than PIB negative patients (1.29, range 1.24-1.34). Mean annual MMSE decline for the 4 PIB positive patients was 2.9 and that for the 6 PIB negative patients was 1. This pilot study suggests that PIB PET is feasible for the evaluation of PSD and PIB binding may be common in PSD. Whether presence of PIB binding is associated with a more rapid cognitive decline in PSD requires further study to confirm.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aniline Compounds; Binding, Competitive; Biomarkers; Brain; Cognition Disorders; Dementia, Vascular; Disability Evaluation; Female; Humans; Male; Neuropsychological Tests; Pilot Projects; Positron-Emission Tomography; Predictive Value of Tests; Severity of Illness Index; Stroke; Thiazoles

Cerebral amyloid angiopathy (CAA) may be an important predisposing factor for the hemorrhagic complications of recombinant tissue-type plasminogen activator (rt-PA) therapy. We studied patients treated within 3 hours of onset of ischemic stroke with rt-PA using positron emission tomography to compare Pittsburgh compound B (PiB) (a cerebral β-amyloid ligand) retention in those with and without parenchymal hemorrhage (PH) and normal controls. Neocortical PiB retention was higher among patients with PH compared with patients without PH and normal controls, suggesting underlying CAA as a predisposing factor for rt-PA-related hemorrhage. This finding may provide an impetus for the development of a more practical rapid pretreatment screening technique.

Topics: Aged; Aniline Compounds; Benzothiazoles; Cerebral Amyloid Angiopathy; Female; Fibrinolytic Agents; Hemorrhage; Humans; Magnetic Resonance Imaging; Male; Positron-Emission Tomography; Retrospective Studies; ROC Curve; Stroke; Thiazoles; Tissue Plasminogen Activator