Abstract
BackgroundMixed pathology, particularly Alzheimer’s disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and hence, little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). The purpose of this study was to understand whether individual differences in amyloid pathology might explain variations in cognitive impairment among individuals with clinical subcortical VCI (SVCI).MethodsTwenty-two participants with SVCI completed an 11C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global amyloid deposition. Cognitive function was measured using: 1) MOCA; 2) ADAS-Cog; 3) EXIT-25; and 4) specific executive processes including a) Digits Forward and Backwards Test, b) Stroop-Colour Word Test, and c) Trail Making Test. To assess the effect of amyloid deposition on cognitive function we conducted Pearson bivariate correlations to determine which cognitive measures to include in our regression models. Cognitive variables that were significantly correlated with PIB retention values were entered in a hierarchical multiple linear regression analysis to determine the unique effect of amyloid on cognitive function. We controlled for age, education, and ApoE ε4 status.ResultsBivariate correlation results showed that PIB binding was significantly correlated with ADAS-Cog (p < 0.01) and MOCA (p < 0.01); increased PIB binding was associated with worse cognitive function on both cognitive measures. PIB binding was not significantly correlated with the EXIT-25 or with specific executive processes (p > 0.05).Regression analyses controlling for age, education, and ApoE ε4 status indicated an independent association between PIB retention and the ADAS-Cog (adjusted R-square change of 15.0 %, Sig F Change = 0.03). PIB retention was also independently associated with MOCA scores (adjusted R-Square Change of 27.0 %, Sig F Change = 0.02).ConclusionWe found that increased global amyloid deposition was significantly associated with greater memory and executive dysfunctions as measured by the ADAS-Cog and MOCA. Our findings point to the important role of co-existing amyloid deposition for cognitive function in those with a primary SVCI diagnosis. As such, therapeutic approaches targeting SVCI must consider the potential role of amyloid for the optimal care of those with mixed dementia.Trial registrationNCT01027858
Highlights
Mixed pathology, Alzheimer’s disease with cerebrovascular lesions, is reported as the second most common cause of dementia
In assessing the effect of amyloid on cognitive function, we found that increased global amyloid deposition–suggestive of co-existing Alzheimer pathology–was significantly associated with worse cognitive function as indicated by the ADAS-Cog and Montreal Cognitive Assessment (MOCA)
It is reported that approximately 33 % of those with subcortical VCI (SVCI) exhibit amyloid pathology [71]
Summary
Alzheimer’s disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). To assess the effect of amyloid deposition on cognitive function we conducted Pearson bivariate correlations to determine which cognitive measures to include in our regression models. Vascular cognitive impairment can be associated with both large vessel disease and small vessel disease [5]; this study will focus on those with subcortical VCI (SVCI) as this group is suggested to be a more homogenous group of patients that are expected to show greater predictability in their clinical picture, natural history, outcome, and treatment response [6]. People with SVCI display relatively intact episodic memory, but show impairments on measures of executive functions, defined as higher-order cognitive processes underpinning goal directed behaviors [8]
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