Subcortical amyloid load is associated with shape and volume in cognitively normal individuals.

Amyloid-beta (Aß) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical 11 C-Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB-positron emission tomography (PET) scan, and 3-T magnetic resonance imaging (MRI) acquisition of T1-weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex-wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aß was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aß was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aß also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aß is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.

Subcortical amyloid relates to cortical morphology in cognitively normal individuals.

PURPOSE: Amyloid (Aß) brain deposition can occur in cognitively normal individuals and is associated with cortical volume abnormalities. Aß-related volume changes are inconsistent across studies. Since volume is composed of surface area and thickness, the relative contribution of Aß deposition on each of these metrics remains to be understood in cognitively normal individuals. METHODS: A group of 104 cognitively normal individuals underwent neuropsychological assessment, PiB-PET scan, and MRI acquisition. Surface-based cortical analyses were performed to investigate the effects of cortical and subcortical Aß burden on cortical volume, thickness, and surface area. Mediation analyses were used to study the effect of thickness and surface area on Aß-associated volume changes. We also investigated the relationships between structural metrics in clusters with abnormal morphology and regions underlying resting-state functional networks and cognitive performance. RESULTS: Cortical Aß was not associated with cortical morphology. Subcortical Aß burden was associated with changes in cortical volume, thickness, and surface area. Aß-associated volume changes were driven by cortical surface area with or without thickness but never by thickness alone. Aß-associated changes overlapped greatly with regions from the default mode network and were associated with lower performance in visuospatial abilities, episodic memory, and working memory. CONCLUSIONS: In cognitively normal individuals, subcortical Aß is associated with cortical volume, and this effect was driven by surface area with or without thickness. Aß-associated cortical changes were found in the default mode network and affected cognitive performance. Our findings demonstrate the importance of studying subcortical Aß and cortical surface area in normal ageing.

Amyloid burden and white matter hyperintensities mediate age-related cognitive differences.

This study examined the additive versus synergistic contribution of beta-amyloid (Aß) and white matter hyperintensities (WMHs) across 7 cognitive domains in 104 cognitively normal older adults. It also measured the extent to which age-related differences in cognition are driven by measurable brain pathology. All participants underwent neuropsychological assessment along with magnetic resonance imaging and Pittsburg compound B-positron emission tomography imaging for Aß quantification. WMH severity was quantified using the age-related white matter changes scale. Stepwise regressions, moderation, and mediation modeling were performed. Our findings show that Aß deposition single-handedly predicts poorer episodic memory performance and that Aß and WMHs contribute additively to poorer performance in working memory and language while carrying synergistic associations with executive functions and attention. Through mediation modeling, we demonstrated that the influence of age over episodic memory, working memory, executive functions, and language is fully mediated by brain pathology. This study permits to conclude that, in healthy older adults, (1) Aß burden and WMHs have synergistic associations with some cognitive domains and (2) age-related differences in most cognitive domains are driven by brain pathology associated with dementia.

Education as a Moderator of the Relationship Between Episodic Memory and Amyloid Load in Normal Aging.

The current study explored whether education, a proxy of cognitive reserve, modifies the association between episodic memory (EM) performance and ßeta-amyloid load (Aß), a biomarker of Alzheimer's disease, in a cohort of cognitively normal older adults. One hundred and four participants (mean age 73.3 years) evenly spread out in three bands of education were recruited. Participants underwent neuropsychological assessment, structural MRI as well as PET imaging to quantify Aß load. Moderation analyses and the Johnson-Neyman technique were carried out to examine the interaction of education with Aß load to predict EM performance. Linear regressions were then performed within each group of education to better illustrate the interaction effect (all analyses were controlled for age and sex). The interaction between education and Aß load was significant (p < .05) for years of education, reaching a cutoff point of 13.5 years, above which the relationship between Aß load and EM was no longer significant. Similarly, significant associations were found between Aß and EM among participants with secondary (p < .01) and pre-university education (p < .01), but not with a university degree (p = .253). EM performance is associated with Aß load in cognitively normal older individuals, and this relationship is moderated by educational attainment.

A Qualitative Impairment in Face Perception in Alzheimer's Disease: Evidence from a Reduced Face Inversion Effect.

Prevalent face recognition difficulties in Alzheimer's disease (AD) have typically been attributed to the underlying episodic and semantic memory impairment. The aim of the current study was to determine if AD patients are also impaired at the perceptual level for faces, more specifically at extracting a visual representation of an individual face. To address this question, we investigated the matching of simultaneously presented individual faces and of other nonface familiar shapes (cars), at both upright and inverted orientation, in a group of mild AD patients and in a group of healthy older controls matched for age and education. AD patients showed a reduced inversion effect (i.e., larger performance for upright than inverted stimuli) for faces, but not for cars, both in terms of error rates and response times. While healthy participants showed a much larger decrease in performance for faces than for cars with inversion, the inversion effect did not differ significantly for faces and cars in AD. This abnormal inversion effect for faces was observed in a large subset of individual patients with AD. These results suggest that AD patients have deficits in higher-level visual processes, more specifically at perceiving individual faces, a function that relies on holistic representations specific to upright face stimuli. These deficits, combined with their memory impairment, may contribute to the difficulties in recognizing familiar people that are often reported in patients suffering from the disease and by their caregivers.