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

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 β deposition. Conclusions —Compared with subjects without Alzheimer’s disease–like A β deposition, those with A β deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. A β was associated with changes in multiple cognitive domains. ( Stroke . 2015;46:3074-3080. DOI: STRIDE study, we recruited consecutive stroke/TIA subjects admit- ted to the acute stroke unit of a University Affiliated Hospital during a 2-year period (2009–2010). We aimed to study the rate and predictors of cognitive decline over a period of 5 years in stroke/TIA patients without dementia before the index event. Cognitive assessment, in- cluding Clinical Dementia Rating (CDR) scale, 4 Cantonese Mini-Mental State Examination (MMSE), 5 and the Hong Kong version of the Montreal Cognitive Assessment (MoCA), 6 were performed on subjects at 3 to 6 months (baseline) after the index event to index gen- eral cognition. Then subjects were further invited to return for annual follow-up. This study analyzed the data collected ≤ 3 years. This substudy included a sample of 72 subjects with cognitive impairment (CDR grade ≥ 0.5) from the STRIDE study. Clinical diag- noses were made by 2 neurologists specialized in dementia (V.C.T.M. and L.A.). Thirty-six subjects had CDR grade of ≥ 1 and met the cri- teria for dementia according to Diagnostic and Statistical Manual of Mental Disorders , 4th edition, Text Revision. 7 Thirty-six subjects were diagnosed as mild cognitive impairment on basis of the frame-work proposed by the International Working Group on mild cognitive impairment 8 : objective cognitive impairment was defined as scores be-low the established cutoff for impairment on the MMSE or MoCA, 5,6 and criteria for subjective cognitive complaints and perseveration of daily functioning were evaluated as part of the assessment of CDR rating. 4 In addition, we interviewed the subject’s reliable informant or caregiver to obtain information about their cognitive condition before the index event. We excluded subjects with known history of prob-able AD before the index event, which was defined by the presence of dementia or a history of progressive cognitive decline in the ab-sence of prior stroke/TIA history and relevant cerebrovascular lesions on neuroimaging, fitting the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria. 3 All subjects received 11 C-PiB PET scan. With reference to 11 C-PiB PET findings, following obtained: caused by drop-out subjects, we used repeated measures ANCOVA to do a subgroup analysis in 59 subjects who completed the 3-year follow- up. ANCOVA was applied to compare test performance and changes between or within groups. Bonferroni correction was used to adjust for type I error for multiple comparisons. To further evaluate the effects of A β retention on cognition, linear regression analyses were conducted between the global PiB SUVR with cognitive scores at different time points and the subsequent changes at different stages. Normality of residuals and linearity between dependent variable and predictor was verified. All comparisons and correlations were corrected for age and years of education on an a priori basis. Statistical analyses were performed using IBM SPSS Statistics version 20 for Windows. artery occlusion ( A 1). CT showed multiple lacunes ( A 2) and severe medial temporal lobe atrophy (MTLA rating=3; A 3). Carbon- 11-labeled Pittsburgh compound B ( 11 C-PiB) positron emission tomography (PET) showed Alzheimer’s disease–like PiB retention (global PiB SUVR=1.83; A 4). She had no cognitive complaints before the index event. After the index event, her MMSE score declined progres- sively from 14 (baseline) to 3 (year 3). B , Pure VCI (pVCI): a 75-year-old lady with 3 years of education was admitted to hospital because of stroke presenting with left-sided weakness and slurred speech. Magnetic resonance imaging showed acute right infarct in corona radi- ata ( B 1), multiple lacunes, severe white matter changes ( B 2), and moderate MTLA (MTLA rating=2; B 3); 11 C-PiB PET showed no abnormal PiB retention (global PiB SUVR=1.41; B 4). After stroke, she presented with acute cognitive decline in the short term but improvement in cognition was observed at follow-up (baseline, MMSE=22; year 1, MMSE=17; year 2, MMSE=19; year 3, MMSE=21). MMSE indicates Mini-Mental State Examination; and SUVR, standard uptake value ratio.