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Amyloid and vascular cognitive impairment : a pilot study of frequency and impact Dao, Dai Trang Thi

Abstract

Background Traditionally, Alzheimer’s disease (AD) and vascular cognitive impairment (VCI) were considered to be distinct and unrelated; however, increasing evidence is demonstrating an overlap between AD and VCI pathology. As such, the current criteria for the clinical diagnosis of VCI may not distinguish those with cognitive impairment exclusively due to subcortical ischemic small vessel disease from those with mixed vascular and AD pathology. Furthermore, it is unclear how co-existing amyloid pathology may affect cognitive function in people with VCI. Objectives: 1) To determine the frequency of mixed VCI-amyloid pathology (mixed VCI) in patients clinically diagnosed with VCI. 2) To explore the impact of co-existing amyloid pathology on cognitive function in people with VCI. Methods This is a cross sectional analysis of data acquired from a randomized controlled trial investigating the effects of aerobic exercise training on cognitive function in people with VCI. Twenty-four participants – 18 participants with VCI and 6 normal controls – completed PET imaging using Pittsburgh Compund-B (PiB) to quantify amyloid burden. Participants with VCI who exhibited PiB uptake 2 standard deviations above the mean of controls were considered to have significant PiB binding and were classified as PiB-positive and to have mixed VCI. To determine the effect of amyloid pathology on cognitive function we collected the following cognitive measures: 1) ADAS-Cog; 2) EXIT-25; and 3) Three executive processes including a) Digits Forward and Backward Test, b) Stroop Test, c) Trail Making Test (Parts A & B). A Pearson correlation coefficient was used to determine the association between PiB uptake and cognitive function. Results Eight out of 18 (44%) participants were PiB-positive and 10 (56%) participants were PiB-negative. PiB-positive and PiB-negative groups did not differ in cognitive functioning (p>0.05), however, increased PiB uptake was associated with greater cognitive dysfunction as measured by the MOCA (r=-0.63, p<0.05) and ADAS-Cog (r=0.61, p<0.05) after controlling for age, gender, and education. Conclusion Almost half of the individuals diagnosed with VCI had co-existing amyloid pathology. Critically, increased amyloid was associated with greater memory and executive dysfunction. As such, amyloid deposition plays a key role in cognitive impairments in people with mixed VCI.

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