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Introduction: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (Aβ) deposition. This study aimed to investigate the effects of Aβ and microglial responses on global cognitive impairment., Methods: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent 11 C-PK11195 and 11 C-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between Aβ load and global cognition was assessed., Results: Aβ load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between Aβ load and global cognitive ratings was partially mediated by the microglial response., Discussion: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated Aβ on cognition., Highlights: This was a longitudinal study of amyloid beta (Aβ), microglial responses, and global cognitive performance. Aβ and microglial responses both affect cognition in early Alzheimer's disease. Microglial response partially mediates the effect of Aβ on cognition in later stages., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: Early symptoms in young onset Alzheimer's disease (YOAD) may be misinterpreted, causing delayed diagnosis. This population-based study aimed to map morbidity prior to YOAD diagnosis., Methods: In a register-based incidence density matched nested case-control study, we examined hospital-diagnosed morbidity for people diagnosed with YOAD in Danish memory clinics during 2016-2020 compared to controls in a 10-year period. Conditional logistic regression produced incidence rate ratios (IRRs)., Results: The study included 1745 cases and 5235 controls. YOAD patients had a higher morbidity burden in the year immediately before dementia diagnosis, for certain disorders up to 10 years before. This was especially evident for psychiatric morbidity with the highest increased IRRs throughout the entire period and IRR 1.43 (95% confidence interval 1.14-1.79) in the 5-10-years before dementia diagnosis., Discussion: YOAD patients display a different pattern of morbidity up to 10 years prior to diagnosis. Awareness of specific alterations in morbidity may improve efforts toward a timely diagnosis., Highlights: Retrospective, nested case-control study of young onset Alzheimer's disease (YOAD). YOAD cases had a higher morbidity burden than controls. YOAD cases had a higher psychiatric morbidity burden up to 10 years before diagnosis. Altered morbidity patterns could serve as an early warning sign of YOAD., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning., Methods: Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (P t O 2 )., Results: At baseline, poor cognitive performance and regional cortical thinning correlated with lower CBF and CBV, with higher MTT and CTH and with low P t O 2 across the cortex. Cognitive decline over time was associated with increasing whole brain relative transit time heterogeneity (RTH = CTH/MTT)., Discussion: Our results confirm the importance of microvascular pathology in AD. Deteriorating microvascular hemodynamics may cause hypoxia, which is known to precipitate amyloid retention., (Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease., Methods: The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour × 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy., Results: Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of ≥66.6% resulted in significant positive effects on single-task physical performance and dual-task performance., Discussion: Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease., (Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)