The semantic storage loss score: An Algorithm for measuring an individual's level of semantic storage loss due to temporal lobe damage in neurodegenerative disease.

Anomia is common in Primary Progressive Aphasia (PPA), and there is considerable evidence that semantic problems (as opposed to impaired access to output word phonology) exist in many PPA individuals irrespective of their strict subtype, including a loss of representations from semantic memory, which is typical for people with the semantic variant of PPA. In this manuscript we present a straightforward novel clinical algorithm that quantifies this degree of semantic storage impairment. We sought to produce an algorithm by employing tasks that would measure key elements of semantic storage loss: a) whether an unrecalled name could be retrieved with cues; b) if performance for items was consistent across tasks; and c) the degree to which a participant's performance was related to general severity of cognitive impairment rather than semantic loss. More specifically, these tasks were given to 28 individuals with PPA (12 participants had a clinical diagnosis of atypical Alzheimer's Disease with the logopenic variant of PPA; the remaining 16 participants received a clinical diagnosis of Frontotemporal dementia (11 were classified as the non-fluent variant of PPA and five were the semantic variant of PPA). Scores from these tasks produced a single omnibus semantic memory storage loss score (SSL score) for each person that ranged from 0.0 to 1.0, with scores closer to 0 more indicative of semantic storage loss. Indeed, supporting the hypothesis that our scores measure the degree of semantic storage loss, we found participants with the semantic variant of PPA had the lowest scores, and SSL scores could predict the degree of hypometabolism in the anterior temporal lobe; even when only people with the logopenic variant of PPA were examined. Thus, these scores show promise quantitating the degree of a person's semantic representation loss.

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.

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.

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.

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.

Structural brain differences between monolingual and multilingual patients with mild cognitive impairment and Alzheimer disease: Evidence for cognitive reserve.

Two independent lines of research provide evidence that speaking more than one language may 1) contribute to increased grey matter in healthy younger and older adults and 2) delay cognitive symptoms in mild cognitive impairment (MCI) or Alzheimer disease (AD). We examined cortical thickness and tissue density in monolingual and multilingual MCI and AD patients matched (within Diagnosis Groups) on demographic and cognitive variables. In medial temporal disease-related (DR) areas, we found higher tissue density in multilingual MCIs versus monolingual MCIs, but similar or lower tissue density in multilingual AD versus monolingual AD, a pattern consistent with cognitive reserve in AD. In areas related to language and cognitive control (LCC), both multilingual MCI and AD patients had thicker cortex than the monolinguals. Results were largely replicated in our native-born Canadian MCI participants, ruling out immigration as a potential confound. Finally, multilingual patients showed a correlation between cortical thickness in LCC regions and performance on episodic memory tasks. Given that multilinguals and monolinguals were matched on memory functioning, this suggests that increased gray matter in these regions may provide support to memory functioning. Our results suggest that being multilingual may contribute to increased gray matter in LCC areas and may also delay the cognitive effects of disease-related atrophy.

Increased neural efficiency in the temporal association cortex as the result of semantic task repetition.

We examined the effect of semantic task repetition and of alternating between tasks on cerebral blood flow in three H(2) (15)O positron emission tomography experiments. We found that repeatedly performing semantic tasks resulted in a reduction in cerebral blood flow to the left temporal association cortex similar to that found in priming experiments even though here there was no repetition of stimuli. Although the same effect was found in two different tasks (word meaning judgments and picture naming), it was only present when the same task was repeated on consecutive scans and not when the subjects alternated from scan to scan between tasks. We propose that there is a neural efficiency which develops in the association cortex of the temporal lobe as a result of repeatedly performing a semantic task. This efficiency is abolished by interruptions such as performing a different task.