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

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

doi:10.1186/s12877-017-0522-4

Abstract

BackgroundTo 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).MethodsThis 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 11C 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.ResultsHigher PIB retention was significantly associated with greater decrements in set shifting (Trail Making Test, adjusted R2 = 35.3%, p = 0.002), attention and conflict resolution (Stroop Test, adjusted R2 = 33.4%, p = 0.01), and information processing speed (Digit Symbol Substitution Test, adjusted R2 = 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 R2 = 49.1%, p = 0.04). PIB retention was not significantly associated with change in ADAS-Cog and Verbal Digit Span Test (p > 0.05).ConclusionsSymptoms associated with SIVCI may be amplified by secondary Aβ pathology.Trial registrationClinicalTrials.gov, NCT01027858, December 7, 2009.

Highlights

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)
Molecular studies indicate a close interaction between Alzheimer’s disease (AD) and SIVCI pathology [8, 9]; yet, few studies have been conducted to investigate the association between Aβ and cognitive function in SIVCI [10,11,12]
Compared with the participants in the randomized controlled trial (RCT) that did not complete Pittsburgh Compound-B (PIB) scans, this subset was similar in age, but had a higher mean Montreal Cognitive Assessment (MOCA) score

Summary

Introduction

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). Alzheimer’s disease (AD) and subcortical ischemic vascular cognitive impairment (SIVCI) are the two most common causes of cognitive dysfunction [1], but people often present with mixed pathology [2]. Few studies have considered mixed pathology from a primary SIVCI diagnosis perspective. It is important to consider AD pathology within an SIVCI diagnosis as both share common pathogenic mechanisms – studies indicate a positive feedback loop effect between Aβ and cerebrovascular dysfunction. Molecular studies indicate a close interaction between AD and SIVCI pathology [8, 9]; yet, few studies have been conducted to investigate the association between Aβ and cognitive function in SIVCI [10,11,12]

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Results

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Conclusion