Effects of Anosognosia on Perceived Stress and Cortisol Levels in Alzheimer's Disease

Anosognosia, or unawareness of one's own cognitive deficits, may cause issues when measuring perceived stress and cortisol levels in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). The goal of this study was to examine the effects of anosognosia on perceived stress and salivary cortisol levels in normal elderly (NE) adults, MCI individuals, newly diagnosed AD patients, and long-lasting AD patients, suspected to show more anosognosia. An anosognosia index for perceived stress was computed by subtracting the score on the Perceived Stress Scale measured in the participants and their relative. Cortisol levels were measured four times a day over two nonconsecutive days. Greater anosognosia for dementia correlated with greater anosognosia for perceived stress in the group as a whole. However, no correlation between cortisol levels and either anosognosia for dementia or perceived stress was observed. Our results suggest that measuring perceived stress in AD patients may be influenced by anosognosia

MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders

Understanding complex diseases such as sporadic Alzheimer disease (AD) has been a major challenge. Unlike the familial forms of AD, the genetic and environmental risks factors identified for sporadic AD are extensive. MicroRNAs are one of the major noncoding RNAs that function as negative regulators to silence or suppress gene expression via translational inhibition or message degradation. Their discovery has evoked great excitement in biomedical research for their promise as potential disease biomarkers and therapeutic targets. Key microRNAs have been identified as essential for a variety of cellular events including cell lineage determination, proliferation, apoptosis, DNA repair, and cytoskeletal organization; most, if not all, acting to fine-tune gene expression at the post-transcriptional level in a host of cellular signaling networks. Dysfunctional microRNA-mediated regulation has been implicated in the pathogenesis of many disease states. Here, the current understanding of the role of miRNAs in the central nervous system is reviewed with emphasis on their impact on the etiopathogenesis of sporadic AD

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

This study examined the additive versus synergistic contribution of beta-amyloid (Aβ) 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 Aβ 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 Aβ deposition single-handedly predicts poorer episodic memory performance and that Aβ 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) Aβ 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 (Aβ) brain deposition can occur in cognitively normal individuals and is associated with cortical volume abnormalities. Aβ-related volume changes are inconsistent across studies. Since volume is composed of surface area and thickness, the relative contribution of Aβ 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 Aβ burden on cortical volume, thickness, and surface area. Mediation analyses were used to study the effect of thickness and surface area on Aβ-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 Aβ was not associated with cortical morphology. Subcortical Aβ burden was associated with changes in cortical volume, thickness, and surface area. Aβ-associated volume changes were driven by cortical surface area with or without thickness but never by thickness alone. Aβ-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 Aβ is associated with cortical volume, and this effect was driven by surface area with or without thickness. Aβ-associated cortical changes were found in the default mode network and affected cognitive performance. Our findings demonstrate the importance of studying subcortical Aβ and cortical surface area in normal agein

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 βeta-amyloid load (Aβ), 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 Aβ load. Moderation analyses and the Johnson–Neyman technique were carried out to examine the interaction of education with Aβ 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 Aβ load was significant (p < .05) for years of education, reaching a cutoff point of 13.5 years, above which the relationship between Aβ load and EM was no longer significant. Similarly, significant associations were found between Aβ and EM among participants with secondary (p < .01) and preuniversity education (p < .01), but not with a university degree (p = .253). EM performance is associated with Aβ load in cognitively normal older individuals, and this relationship is moderated by educational attainment

The Relation Between Depressive Symptoms and Semantic Memory in Amnestic Mild Cognitive Impairment and in Late-Life Depression

Semantic deficits have been documented in the prodromal phase of Alzheimer’s disease, but it is unclear whether these deficits are associated with non-cognitive manifestations. For instance, recent evidence indicates that cognitive deficits in elders with amnestic mild cognitive impairment (aMCI) are modulated by concomitant depressive symptoms. The purposes of this study were to (i) investigate if semantic memory impairment in aMCI is modulated according to the presence (aMCI-D group) or absence (aMCI group) of depressive symptoms, and (ii) compare semantic memory performance of aMCI and aMCI-D groups to that of patients with late-life depression (LLD). Seventeen aMCI, 16 aMCI-D, 15 LLD, and 26 healthy control participants were administered a semantic questionnaire assessing famous person knowledge. Results showed that performance of aMCI-D patients was impaired compared to the control and LLD groups. However, in the aMCI group performance was comparable to that of all other groups. Overall, these findings suggest that semantic deficits in aMCI are somewhat associated with the presence of concomitant depressive symptoms. However, depression alone cannot account solely for the semantic deficits since LLD patients showed no semantic memory impairment in this study. Future studies should aim at clarifying the association between depression and semantic deficits in older adults meeting aMCI criteria.Instituts de recherche en santé du Canada (IRSC) IAO-8467

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

Making the Case for Accelerated Withdrawal of Aducanumab

The controversial approval in June 2021 by the Food and Drug Administration (FDA) of aducanumab (marketed as Aduhelm), Biogen's monoclonal antibody for patients with Alzheimer's disease, raises significant concerns for the dementia field and drug approval process, considering its lack of adequate evidence for clinical efficacy, safety issues, and cost. On 15 December 2021, an international group of clinicians, basic science experts, psychological and social science researchers, lay people with lived experience of dementia, and advocates for public health met to discuss making a recommendation for whether aducanumab's approval should be withdrawn. Attendees considered arguments both in favor of and in opposition to withdrawal and voted unanimously to recommend that the FDA withdraw its approval for aducanumab and to support the Right Care Alliance's filing of a formal Citizen Petition to this effect

Deficits of knowledge versus executive control in semantic cognition: Insights from cued naming

Deficits of semantic cognition in semantic dementia and in aphasia consequent on CVA (stroke) are qualitatively different. Patients with semantic dementia are characterised by progressive degradation of central semantic representations, whereas multimodal semantic deficits in stroke aphasia reflect impairment of executive processes that help to direct and control semantic activation in a task-appropriate fashion [Jefferies, E., & Lambon Ralph, M. A. (2006). Semantic impairment in stroke aphasia vs. semantic dementia: A case-series comparison. Brain 129, 2132-2147]. We explored interactions between these two aspects of semantic cognition by examining the effects of cumulative phonemic cueing on picture naming in case series of these two types of patient. The stroke aphasic patients with multimodal semantic deficits cued very readily and demonstrated near-perfect name retrieval when cumulative phonemic cues reached or exceeded the target name's uniqueness point. Therefore, knowledge of the picture names was largely intact for the aphasic patients, but they were unable to retrieve this information without cues that helped to direct activation towards the target response. Equivalent phonemic cues engendered significant but much more limited benefit to the semantic dementia patients: their naming was still severely impaired even when most of the word had been provided. In contrast to the pattern in the stroke aphasia group, successful cueing was mainly confined to the more familiar un-named pictures. We propose that this limited cueing effect in semantic dementia follows from the fact that concepts deteriorate in a graded fashion [Rogers, T. T., Lambon Ralph, M. A., Garrard, P., Bozeat, S., McClelland, J. L., & Hodges, J. R., et al. (2004). The structure and deterioration of semantic memory: A neuropsychological and computational investigation. Psychological Review 111, 205-235]. For partially degraded items, the residual conceptual knowledge may be insufficient to drive speech production to completion but these items might reach threshold when they are bolstered by cues. (C) 2007 Elsevier Ltd. All rights reserved