Association of critically short telomeres with brain and blood markers of ageing and Alzheimer's disease in older adults.

Background: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults.

Decoding meditation mechanisms underlying brain preservation and psycho-affective health in older expert meditators and older meditation-naive participants.

Meditation is a mental training approach that can improve mental health and well-being in aging. Yet the underlying mechanisms remain unknown. The Medit-Ageing model stipulates that three mechanisms - attentional, constructive, and deconstructive - upregulate positive psycho-affective factors and downregulate negative ones.

Multimodal neuroimaging correlates of spectral power in NREM sleep delta sub-bands in cognitively unimpaired older adults.

Study Objectives: In aging, reduced delta power (0.5-4 Hz) during N2 and N3 sleep has been associated with gray matter (GM) atrophy and hypometabolism within frontal regions. Some studies have also reported associations between N2 and N3 sleep delta power in specific sub-bands and amyloid pathology.

Respective influence of beta-amyloid and APOE ε4 genotype on medial temporal lobe subregions in cognitively unimpaired older adults.

Medial temporal lobe (MTL) subregions are differentially affected in Alzheimer's disease (AD), with a specific involvement of the entorhinal cortex (ERC), perirhinal cortex and hippocampal cornu ammonis (CA)1. While amyloid (Aβ) and APOEε4 are respectively the first molecular change and the main genetic risk factor in AD, their links with MTL atrophy remain relatively unclear. Our aim was to uncover these effects using baseline data from 130 participants included in the Age-Well study, for whom ultra-high-resolution structural MRI, amyloid-PET and APOEε4 genotype were available.

Rapid Eye Movement Sleep, Neurodegeneration, and Amyloid Deposition in Aging.

Objective: Rapid eye movement (REM) sleep is markedly altered in Alzheimer's disease (AD), and its reduction in older populations is associated with AD risk. However, little is known about the underlying brain mechanisms. Our objective was to investigate the relationships between REM sleep integrity and amyloid deposition, gray matter volume, and perfusion in aging.

Depressive symptoms in cognitively unimpaired older adults are associated with lower structural and functional integrity in a frontolimbic network.

Subclinical depressive symptoms are associated with increased risk of Alzheimer's disease (AD), but the brain mechanisms underlying this relationship are still unclear. We aimed to provide a comprehensive overview of the brain substrates of subclinical depressive symptoms in cognitively unimpaired older adults using complementary multimodal neuroimaging data. We included cognitively unimpaired older adults from the baseline data of the primary cohort Age-Well (n = 135), and from the replication cohort ADNI (n = 252).

Effect of an 18-Month Meditation Training on Regional Brain Volume and Perfusion in Older Adults: The Age-Well Randomized Clinical Trial.

Importance: No lifestyle-based randomized clinical trial directly targets psychoaffective risk factors of dementia. Meditation practices recently emerged as a promising mental training exercise to foster brain health and reduce dementia risk.

Objective: To investigate the effects of meditation training on brain integrity in older adults.

Relationships between diabetes-related vascular risk factors and neurodegeneration biomarkers in healthy aging and Alzheimer's disease.

Vascular risk factors such as hyperglycemia and platelet hyperactivation play a significant role in type 2 diabetes (T2D), a risk factor for AD. We investigated the relationships between glycemia levels, platelet indices (platelet count; mean platelet volume (MPV)) and AD neuroimaging markers in 105 cognitively unimpaired adults, including 21 amyloid-negative older adults (Aβ-neg controls), and 45 amyloid-positive patients with mild cognitive impairment or dementia (Aβ-pos patients). We assessed between-group differences on the two T2D-related vascular risk factors, then the association between blood parameters and multimodal neuroimaging (structural MRI, F-fluorodeoxyglucose, and F-florbetapir-PET) in cognitively unimpaired adults and Aβ-pos patients using multiple regressions.

Plasma Levels of Tissue-Type Plasminogen Activator (tPA) in Normal Aging and Alzheimer's Disease: Links With Cognition, Brain Structure, Brain Function and Amyloid Burden.

Tissue-type plasminogen activator (tPA) is a protease known for its fibrinolytic action but is also involved in physiological and pathophysiological aging processes; including amyloid elimination and synaptic plasticity. The aim of the study was to investigate the role of tPA in cognitive and brain aging. Therefore, we assessed the links between tPA plasma concentration and cognition, structural MRI, FDG-PET and Flobetapir-PET neuroimaging in 155 cognitively unimpaired adults (CUA, aged 20-85 years old) and 32 patients with Alzheimer's disease (ALZ).

Vascular Health Is Associated With Functional Connectivity Decline in Higher-Order Networks of Older Adults.

Background: Poor vascular health may impede brain functioning in older adults, thus possibly increasing the risk of cognitive decline and Alzheimer's disease (AD). The emerging link between vascular risk factors (VRF) and longitudinal decline in resting-state functional connectivity (RSFC) within functional brain networks needs replication and further research in independent cohorts.

Method: We examined 95 non-demented older adults using the IMAP+ cohort (Caen, France).

Role of Cardiovascular Risk Factors on the Association Between Physical Activity and Brain Integrity Markers in Older Adults.

Background And Objectives: Physical activity has been associated with a decreased risk for dementia, but the mechanisms underlying this association remain to be determined. Our objective was to assess whether cardiovascular risk factors mediate the association between physical activity and brain integrity markers in older adults.

Methods: At baseline, participants from the Age-Well study completed a physical activity questionnaire and underwent cardiovascular risk factors collection (systolic blood pressure, body mass index [BMI], current smoker status, and high-density lipoprotein cholesterol, total cholesterol, and insulin levels) and multimodal neuroimaging (structural MRI, diffusion MRI, FDG-PET, and florbetapir PET).

Subjective cognitive decline: opposite links to neurodegeneration across the Alzheimer's continuum.

Subjective memory decline is associated with neurodegeneration and increased risk of cognitive decline in participants with no or subjective cognitive impairment, while in patients with mild cognitive impairment or Alzheimer's-type dementia, findings are inconsistent. Our aim was to provide a comprehensive overview of subjective memory decline changes, relative to objective memory performances, and of their relationships with neurodegeneration, across the clinical continuum of Alzheimer's disease. Two hundred participants from the primary cohort and 731 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) replication cohort were included.

Sex-specificities in anxiety and depressive symptoms across the lifespan and their links with multimodal neuroimaging.

Background: Anxiety and depressive symptoms are associated with impaired well-being, higher risk of developing psychoaffective disorders and are risk factors for Alzheimer's disease (AD). To further understand their relevance and the mechanisms underlying their link with AD, our aims were to assess how anxiety and depressive symptoms changed with age and related to AD neuroimaging biomarkers across the adult lifespan, while also exploring sex specificities.

Methods: 210 cognitively normal participants aged 19-86 years (101 men, 109 women) completed assessments of anxiety and depressive symptoms with the STAI-A and MADRS respectively, and neuroimaging measurements including structural MRI, FDG-PET and amyloid-PET.

Longitudinal Changes in Hippocampal Network Connectivity in Alzheimer's Disease.

Objective: The hippocampus is connected to 2 distinct cortical brain networks, the posterior-medial and the anterior-temporal networks, involving different medial temporal lobe (MTL) subregions. The aim of this study was to assess the functional alterations of these 2 networks, their changes over time, and links to cognition in Alzheimer's disease.

Methods: We assessed MTL connectivity in 53 amyloid-β-positive patients with mild cognitive impairment and AD dementia and 68 healthy elderly controls, using resting-state functional magnetic resonance imaging, cross-sectionally and longitudinally.

Evaluation of the early-phase [F]AV45 PET as an optimal surrogate of [F]FDG PET in ageing and Alzheimer's clinical syndrome.

Dual-phase [F]AV45 positron emission tomography (PET) is highly promising in the assessment of neurodegenerative diseases, allowing to obtain information on both neurodegeneration (early-phase; eAV45) and amyloid deposition (late-phase; lAV45) which are highly complementary; yet eAV45 needs further evaluation. This study aims at validating eAV45 as an optimal proxy of [F]FDG PET in a large mixed-population of healthy ageing and Alzheimer's clinical syndrome participants (n = 191) who had [F]FDG PET, eAV45 and lAV45 scans. We found early time frame 0-4 min to give maximal correlation with [F]FDG PET and minimal correlation with lAV45.

Brain Glucose Metabolism in Cerebral Amyloid Angiopathy: An FDG-PET Study.

Background And Purpose: The in vivo diagnosis of cerebral amyloid angiopathy (CAA) is currently based on the Boston criteria, which largely rely on hemorrhagic features on brain magnetic resonance imaging. Adding to these criteria F-fluoro-deoxy-D-glucose (FDG) positron emission tomography, a widely available imaging modality, might improve their accuracy. Here we tested the hypothesis that FDG uptake is reduced in posterior cortical areas, particularly the primary occipital cortex, which pathologically bear the brunt of vascular Aβ deposition.

Association of quality of life with structural, functional and molecular brain imaging in community-dwelling older adults.

Background: As the population ages, maintaining mental health and well-being of older adults is a public health priority. Beyond objective measures of health, self-perceived quality of life (QoL) is a good indicator of successful aging. In older adults, it has been shown that QoL is related to structural brain changes.

Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer's disease.

Background: White matter hyperintensities (WMH) are frequently found in Alzheimer's disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction.

Resting state functional atlas and cerebral networks in mouse lemur primates at 11.7 Tesla.

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microcebus murinus) is one of the smallest and more phylogenetically distant primates as compared to humans.

White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition.

Background: White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults.

Methods: One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort).

Association of Sleep-Disordered Breathing With Alzheimer Disease Biomarkers in Community-Dwelling Older Adults: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increasing evidence suggests that sleep-disordered breathing (SDB) increases the risk of developing Alzheimer clinical syndrome. However, the brain mechanisms underlying the link between SDB and Alzheimer disease are still unclear.

Objective: To determine which brain changes are associated with the presence of SDB in older individuals who are cognitively unimpaired, including changes in amyloid deposition, gray matter volume, perfusion, and glucose metabolism.

Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time.

Background: Subjective cognitive decline (SCD) defines a heterogeneous population, part of which having Alzheimer's disease (AD). We aimed at characterizing SCD populations according to whether or not they referred to a memory clinic, by assessing the factors associated with increased AD risk.

Methods: Seventy-eight cognitively unimpaired older adults from the IMAP+ study (Caen) were included, amongst which 28 healthy controls (HC) and 50 SCD recruited from the community (SCD-community; n = 23) or from a memory clinic (SCD-clinic; n = 27).