Cerebrovascular disease, β-amyloid, and cognition in aging

Abstract

The present study evaluated cerebrovascular disease (CVD), β-amyloid (Aβ), and cognition in clinically normal elderly adults. Fifty-four participants underwent magnetic resonance imaging (MRI), Pittsburgh compound B (PIB)-positron emission tomography (PET) imaging, and neuropsychological evaluation. High white matter hyperintensity burden and/or presence of infarct defined CVD status (CVD-: n = 27; CVD+: n = 27). PIB-positron emission tomography ratios of Aβ deposition were extracted using Logan plotting (cerebellar reference). Presence of high levels of Aβ in prespecified regions determined PIB status (PIB-: n = 33; PIB+: n = 21). Executive functioning and episodic memory were measured using composite scales. CVD and Aβ, defined as dichotomous or continuous variables, were unrelated to one another. CVD+ participants showed lower executive functioning (p = 0.001) when compared with CVD- individuals. Neither PIB status nor amount of Aβ affected cognition (ps ≥ 0.45), and there was no statistical interaction between CVD and PIB on either cognitive measure. Within this spectrum of normal aging CVD and Aβ aggregation appear to be independent processes with CVD primarily affecting cognition.

Figure 1. Representative brain images from the four categories of brain pathology

Presence of infarct or WMH volume > .5% of total intracranial volume defined CVD positivity. DVR values of Global PIB Index > 1.114 or bilateral precuneus/posterior cingulate region > 1.137 defined PIB positivity.

Figure 2. Box and whiskers plot of mean Global PIB Index volume based on CVD(+/−) status

CVD− and CVD+ groups did not differ in Global PIB Index DVR values.

Figure 3. Scatterplot of continuous measures of Global PIB Index volume and white matter hyperintensity volume (reported as percentage of total cranial volume)

Open circles represent individuals with no infarct, grey circles represent subcortical infarct and black circles represent cortical infarct (2 individuals with cortical infarct also had subcortical infarcts). Global PIB Index volume was not related to WMH volume or infarct status. Categorizing Global PIB Index into a dichotomous variable (PIB+/−, based on a cutoff of 2 SD above a young control group), demonstrated by the dashed line, further supported the absence of a relationship between PIB and WMH or infarct; although all individuals with cortical infarct were PIB+. Three individuals were classified as PIB+ due to significant PIB deposition in bilateral precuneus/posterior cingulate region, they are not represented as PIB+ in the present graph.

Figure 4. Executive functioning and episodic memory stratified by CVD(+/−) and PIB(+/−) status

Cognitive performance measures (corrected for age, sex, and education) are represented as Z-scores. a. CVD+ participants show significantly worse executive functioning than CVD− participants (P = 0.001; corrected for age, sex and education). b. PIB+ participants perform worse than PIB− participants (P = 0.095); however after correcting for age, sex and education PIB groups did not differ in executive functioning performance (P = .47). c. & d. Episodic memory performance did not differ based on CVD status (P = .92, corrected for age, sex and education) or PIB status (P = .57, corrected for age, sex and education). * P = 0.001.