Associations between cerebral amyloid and changes in cognitive function and falls risk in subcortical ischemic vascular cognitive impairment

Elizabeth Dao, John R. Best, Ging-Yuek Robin Hsiung, Vesna Sossi, Claudia Jacova, Roger Tam, Teresa Liu-Ambrose

To determine the association between amyloid-beta (Aβ) plaque deposition and changes in global cognition, executive functions, information processing speed, and falls risk over a 12-month period in older adults with a primary clinical diagnosis of subcortical ischemic vascular cognitive impairment (SIVCI). This is a secondary analysis of data acquired from a subset of participants (N = 22) who were enrolled in a randomized controlled trial of aerobic exercise (NCT01027858). The subset of individuals completed an (11)C Pittsburgh compound B (PIB) scan. Cognitive function and falls risk were assessed at baseline, 6-months, and 12-months. Global cognition, executive functions, and information processing speed were measured using: 1) ADAS-Cog; 2) Trail Making Test; 3) Digit Span Test; 4) Stroop Test, and 5) Digit Symbol Substitution Test. Falls risk was measured using the Physiological Profile Assessment. Hierarchical multiple linear regression analyses determined the unique contribution of Aβ on changes in cognitive function and falls risk at 12-months after controlling for experimental group (i.e. aerobic exercise training or usual care control) and baseline performance. To correct for multiple comparisons, we applied the Benjamini-Hochberg procedure to obtain a false discovery rate corrected threshold using alpha = 0.05. Higher PIB retention was significantly associated with greater decrements in set shifting (Trail Making Test, adjusted R(2) = 35.3%, p = 0.002), attention and conflict resolution (Stroop Test, adjusted R(2) = 33.4%, p = 0.01), and information processing speed (Digit Symbol Substitution Test, adjusted R(2) = 24.4%, p = 0.001) over a 12-month period. Additionally, higher PIB retention was significantly associated with increased falls risk (Physiological Profile Assessment, adjusted R(2) = 49.1%, p = 0.04). PIB retention was not significantly associated with change in ADAS-Cog and Verbal Digit Span Test (p > 0.05). Symptoms associated with SIVCI may be amplified by secondary Aβ pathology. ClinicalTrials.gov, NCT01027858 , December 7, 2009.