The Effect of a Multiple Modality Mind-Motor Exercise Intervention on Single and Dual-Task Gait, Balance, and Executive Function, in Community Dwelling Older Adults with a Subjective Cognitive Complaint: A Randomized Controlled Trial.

Cognitive decline disorders are becoming increasingly prevalent, with older adults at increased risk. Combined exercise has been recently explored as an intervention to help to prevent the decline, however cognitive activation in combination with physical activity has yet to be explored. Therefore, the purpose of the study is to determine the effects of multiple modality exercise programs in combination with a mind-motor task and their effects on mobility and cognitive variables. A total of (n=89) older adults (55+ yrs), with subjective cognitive complaints participated in a multiple modality exercise class, three days a week over six months, with the intervention group performing an additional mind-motor exercise. Significant differences were observed in gait variables, with not significant changes in balance or executive function. Multiple-Modality exercise with mind-motor training does yield physiological improvements as well as mobilit

Multiple-Modality Exercise And Mind-Motor Training To Improve Mobility In Older Adults: A Randomized Controlled Trial

Objective: To investigate the effects of multiple-modality exercise with or without additional mind-motor training on mobility outcomes in older adults with subjective cognitive complaints. Methods: This was a 24-week randomized controlled trial with a 28-week no-contact follow-up. Community-dwelling older adults underwent a thrice -weekly, Multiple-Modality exercise and Mind-Motor (M4) training or Multiple-Modality (M2) exercise with an active control intervention (balance, range of motion and breathing exercises). Study outcomes included differences between groups at 24 weeks and after the no-contact follow-up (i.e., 52 weeks) in usual and dual-task (DT, i.e., serial sevens [S7] and phonemic verbal fluency [VF] tasks) gait velocity, step length and cycle time variability, as well as DT cognitive accuracy. Results: 127 participants (mean age 67.5 [7.3] years, 71% women) were randomized to either M2 (n =64) or M4 (n = 63) groups. Participants were assessed at baseline, intervention endpoint (24 weeks), and study endpoint (52 weeks). At 24 weeks, the M2 group demonstrated greater improvements in usual gait velocity, usual step length, and DT gait velocity (VF) compared to the M4 group, and no between- or within-group changes in DT accuracy were observed. At 52 weeks, the M2 group retained the gains in gait velocity and step length, whereas the M4 group demonstrated trends for improvement (p =0.052) in DT cognitive accuracy (VF). Conclusions: Our results suggest that additional mind-motor training was not effective to improve mobility outcomes. In fact, participants in the active control group experienced greater benefits as a result of the intervention

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

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

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

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the devel- opment of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

The use of random forests to classify amyloid brain PET

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.Purpose: To evaluate random forests (RFs) as a supervised machine learning algorithm to classify amyloid brain PET as positive or negative for amyloid deposition and identify key regions of interest for stratification. Methods: The data set included 57 baseline 18F-florbetapir (Amyvid; Lilly, Indianapolis, IN) brain PET scans in participants with severe white matter disease, presenting with either transient ischemic attack/lacunar stroke or mild cognitive impairment from early Alzheimer disease, enrolled in a multicenter prospective observational trial. Scans were processed using the MINC toolkit to generate SUV ratios, normalized to cerebellar gray matter, and clinically read by 2 nuclear medicine physicians with interpretation based on consensus (35 negative, 22 positive). SUV ratio data and clinical reads were used for super- vised training of an RF classifier programmed in MATLAB. Results: A 10,000-tree RF, each tree using 15 randomly selected cases and 20 randomly selected features (SUV ratio per region of interest), with 37 cases for training and 20 cases for testing, had sensitivity = 86% (95% confidence in- terval [CI], 42%–100%), specificity = 92% (CI, 64%–100%), and classification accuracy = 90% (CI, 68%–99%). The most common features at the root node (key regions for stratification) were (1) left posterior cingulate (1039 trees), (2) left middle frontal gyrus (1038 trees), (3) left precuneus (857 trees), (4) right an- terior cingulate gyrus (655 trees), and (5) right posterior cingulate (588 trees). Conclusions: Random forests can classify brain PET as positive or negative for amyloid deposition and suggest key clinically relevant, regional features for classification.CIHR MITNEC C6 || Linda C Campbell Foundation || Lilly-Avid Radiopharmaceuticals

VII. Discours

Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. Methods: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. Results: Six survey rounds comprising 65–79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders–Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. Discussion: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders–Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration

The Vascular Impairment of Cognition Classification Consensus Study

Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. / Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. / Results: VICCCS had a mean of 122 (98–153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. / Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research