Subtle visuomotor difficulties in preclinical Alzheimer's disease

Background: Individuals with preclinical Alzheimer's disease (Pre-AD) present nonimpaired cognition, as measured by standard neuropsychological tests. However, detecting subtle difficulties in cognitive functions may be necessary for an early diagnosis and intervention. Objectives: A new computer-based visuomotor coordination task (VMC) was developed to investigate the possible presence of early visuomotor difficulties in Pre-AD individuals. Associations between VMC task performance and AD biomarkers were studied. The influence of ApoE status on participants' performance was addressed, as well as the relationship between performance and subjective cognitive decline (SCD). Methods: Sixty-six cognitively normal (CN) elders (19 Pre-AD and 47 control participants [CTR]) and 15 patients with AD performed the VMC task, which consisted in executing visually guided goal-directed movements that required the coordination of the visual and motor systems. All participants underwent ApoE analysis and lumbar puncture. CN participants also completed an extensive standard neuropsychological battery. Results: Despite presenting normal cognition in standard tests, Pre-AD participants exhibited higher response times (RTs) to complete the VMC task than CTR (p < .01). Besides, patients with AD showed higher RTs than CTR (p < .001) and Pre-AD (p < .05), and more errors than CTR (p < .005). RTs in ApoE4 carriers were higher than that observed in ApoE4 noncarriers (p < .01). In CN individuals, RTs were related to amyloid β-protein 42 (AB42) biomarker (p < .01) and informant-rated SCD (p < .01). Conclusions: The VMC task is able to discriminate Pre-AD from CTR individuals. Moreover, VMC results are associated with AB42 levels in CN individuals, suggesting that visuomotor dysfunction may be a sensitive marker of Pre-AD

Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples

Introduction: Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer's disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). Methods: We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. Results: The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. Conclusions: While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD

Smaller medial temporal lobe volumes in individuals with subjective cognitive decline and biomarker evidence of Alzheimer's disease—Data from three memory clinic studies

Introduction: Previous studies showed associations of brain volume differences and biomarker evidence for Alzheimer's disease (AD) in subjective cognitive decline (SCD). The consistency of this finding across SCD studies has not been investigated. Methods: We studied gray matter volume differences between SCD subjects with and without cerebrospinal fluid biomarker evidence for AD across three European memory clinic samples (German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia study, Amsterdam, Barcelona). Analysis of covariance models with samples and cerebrospinal fluid biomarkers as between-subject factors were calculated. Results: A significant main effect for AD biomarker (Aβ42− > Aβ42+) in the left medial temporal lobe (MTL) was found, with the absence of main effects for sample or interaction effects between AD biomarker and sample. This indicates consistent lower left MTL volume across three samples in SCD subjects with abnormal Aβ42 levels. Discussion: Our results support the model that in the presence of AD pathology, SCD corresponds to the late preclinical stage (stage 2 of AD) with smaller MTL volumes

Alzheimers Dement

Introduction: Subjectively experienced cognitive decline in older adults is an indicator of increased risk for dementia and is also associated with increased levels of anxiety symptoms. As anxiety is itself emerging as a risk factor for cognitive decline and dementia, the primary question of the present study is whether an 8-week mindfulness-based intervention can significantly reduce anxiety symptoms in patients with subjective cognitive decline (SCD). The secondary questions pertain to whether such changes extend to other domains of psychological, social, and biological functioning (including cognition, self-regulation, lifestyle, well-being and quality of life, sleep, and selected blood-based biomarkers) associated with mental health, older age, and risk for dementia. Methods: SCD-Well is a multicenter, observer-blinded, randomized, controlled, superiority trial, which is part of the Horizon 2020 European Union-funded "Medit-Ageing" project. SCD-Well compares an 8-week mindfulness- and compassion-based intervention specifically adapted for older adults with SCD with a validated 8-week health education program. Participants were recruited from memory clinics in four European sites (Cologne, Germany; London, United Kingdom; Barcelona, Spain; and Lyon, France) and randomized with a 1:1 allocation, stratified by site. Results: The primary outcome, change in anxiety symptoms, and secondary outcomes reflecting psychological, cognitive, social, and biological functioning are assessed at baseline, postintervention, and 4 months after the end of the intervention. Discussion: The study will provide evidence on whether a mindfulness-based intervention can effect changes in anxiety and other risk factors for cognitive decline and dementia in older adults with SCD and will inform the establishment of intervention strategies targeted at improving mental health in older adults