Liu W, Wong A, Au L, Yang J, Wang Z, Leung EYL, et al. Influence of Amyloid-β on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study. Stroke. 2015
The report is based on a substudy of the Stroke Registry Investigating cognitive Decline (STRIDE) study, which recruited consecutive stroke/TIA subjects at a single university-affiliated hospital in Hong Kong over 2-years. Cognitive assessment utilized Clinical Dementia Rating (CDR), Cantonese Mini-Mental State Examination (MMSE)and the Hong Kong version of the Montreal Cognitive Assessment, initially performed 3 to 6 months after the index event, to establish baseline cognitive functioning. A total of 72 subjects with cognitive impairment (defined as CDR ≥0.5) were selected, with 36 having a CDR ≥1 and meeting DSM-IV criteria for dementia and 36 being diagnosed as mild cognitive impairment. Patients with probable AD prior to their vascular event were excluded. All subjects received a C-PiB PET scan. Based on the results, 14 PiB-positive subjects were categorized as having mixed vascular cognitive impairment (mVCI) and 58 PiB-negative subjects were categorized as having pure vascular cognitive impairment (pVCI). Longitudinal cognitive assessments were performed at baseline and years 1, 2, and 3 following the index event using the same measures.
The patients with amyloid-beta deposition on initial imaging had significantly lower MMSE scores at year 3 compared to baseline (p=0.020), as well as lower overall 3-year scores (p=0.037) as compared to the pVCI group. The overall change in MMSE score over 3-years wasnot significant for the pVCI group (p=0.208) with a significant difference in the change in MMSE between the groups score over time (p=0.007). Although the mVCI group had a more rapid annual rate of decline, that amount was constant across years, whereas the pVCI group had a faster decline in cognition over the first year, but remained relatively stable thereafter. The findings were not as dramatic comparing MoCA scores, with a linear mixed model showing a non-significant trend for a difference in changes between the two groups over time (p=0.089). The memory domain had the greatest impact on the differences, with the mVCI group having a significant decline (p=0.038) that was not present in the pVCI group. In addition, quantitative standard uptake value ratios (SUVR) obtained with PET imaging showed that higher PiB SUVR was associated with greater average annual declines on the MMSE (p=0.035), and MoCA (p=0.006; particularly for the visuospatial, p=0.015, and executive function, p=0.023 domains).
This study provides a unique insight into the relationship between vascular and amyloid pathologies on cognitive impairment and dementia. The findings are particularly interesting given how similar the two groups were at baseline, suggesting the potential usefulness of PET imaging in predicting further cognitive deterioration in post-stroke patients. This study also reinforces the need for clinicians to assess for comorbid contributions that could contribute cognitive decline in patients with vascular cognitive impairment as careful management might forestall further worsening related to cerebrovascular disease.
The study does have important limitations, particularly the relatively small sample size in the mVCI group, as well as a high dropout rate (18% due to death or other reasons). In addition, the MoCA was too challenging and not administered in patients with more impaired cognition, possibly resulting in the lack of differences between groups. Brain MRI was not obtained in 40% of the subjects, and additional structural imaging would have allowed more precision in characterizing the subject’s vascular disease burden. Additional longitudinal studies with larger sample sizes and subjects across the spectrum of cognitive deficits will be needed to verify these findings.