Association of subjective cognitive decline with markers of brain pathology in preclinical autosomal dominant Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Gatchel JR
PROVIDER: S-EPMC7397724 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Association of subjective cognitive decline with markers of brain pathology in preclinical autosomal dominant Alzheimer's disease.
Gatchel Jennifer R JR Lopera Francisco F Norton Daniel J DJ Baena Ana A Guzman-Velez Edmarie E Sanchez Justin S JS d'Oleire Uquillas Federico F Schultz Aaron A Vannini Patrizia P Artola Arabiye A Amariglio Rebecca E RE Rentz Dorene M DM Tariot Pierre N PN Reiman Eric M EM Johnson Keith A KA Sperling Reisa A RA Marshall Gad A GA Quiroz Yakeel T YT
Journal of neurology, neurosurgery, and psychiatry 20191224 3
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Project description:Subjective cognitive decline (SCD) is regarded as the first clinical manifestation in the Alzheimer's disease (AD) continuum. Investigating populations with SCD is important for understanding the early pathological mechanisms of AD and identifying SCD-related biomarkers, which are critical for the early detection of AD. With the advent of advanced neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), accumulating evidence has revealed structural and functional brain alterations related to the symptoms of SCD. In this review, we summarize the main imaging features and key findings regarding SCD related to AD, from local and regional data to connectivity-based imaging measures, with the aim of delineating a multimodal imaging signature of SCD due to AD. Additionally, the interaction of SCD with other risk factors for dementia due to AD, such as age and the Apolipoprotein E (ApoE) ɛ4 status, has also been described. Finally, the possible explanations for the inconsistent and heterogeneous neuroimaging findings observed in individuals with SCD are discussed, along with future directions. Overall, the literature reveals a preferential vulnerability of AD signature regions in SCD in the context of AD, supporting the notion that individuals with SCD share a similar pattern of brain alterations with patients with mild cognitive impairment (MCI) and dementia due to AD. We conclude that these neuroimaging techniques, particularly multimodal neuroimaging techniques, have great potential for identifying the underlying pathological alterations associated with SCD. More longitudinal studies with larger sample sizes combined with more advanced imaging modeling approaches such as artificial intelligence are still warranted to establish their clinical utility.
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Project description:Histopathological reports suggest that subregions of the thalamus, which regulates multiple physiological and cognitive processes, are not uniformly affected by Alzheimer's disease. Despite this, structural neuroimaging studies often consider the thalamus as a single region. Identification of in vivo Alzheimer's-dependent volumetric changes in thalamic subregions may aid the characterization of early nuclei-specific neurodegeneration in Alzheimer's disease. Here, we leveraged access to the largest single-mutation cohort of autosomal-dominant Alzheimer's disease to test whether cross-sectional abnormalities in subregional thalamic volumes are evident in non-demented mutation carriers (n = 31), compared to non-carriers (n = 36), and whether subregional thalamic volume is associated with age, markers of brain pathology and cognitive performance. Using automatic parcellation we examined the thalamus in six subregions (anterior, lateral, ventral, intralaminar, medial, and posterior) and their relation to age and brain pathology (amyloid and tau), as measured by PET imaging. No between-group differences were observed in the volume of the thalamic subregions. In carriers, lower volume in the medial subregion was related to increased cortical amyloid and entorhinal tau burden. These findings suggest that thalamic Alzheimer's-related volumetric reductions are not uniform even in preclinical and prodromal stages of autosomal-dominant Alzheimer's disease and therefore, this structure should not be considered as a single, unitary structure in Alzheimer's disease research.
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Project description:ObjectivePhysical activity (PA) has been linked to reduced Alzheimer's disease (AD) risk. However, less is known about its effects in the AD preclinical stage. We aimed to investigate whether greater PA was associated with lower plasma biomarkers of AD pathology, neural injury, reactive astrocytes, and better cognition in individuals with autosomal-dominant AD due to the presenilin-1 E280A mutation who are virtually guaranteed to develop dementia.MethodsTwenty-eight cognitively unimpaired mutation carriers (ages x̄ = 29.28) wore a FitBit Charge-4 for 14 days. We calculated their average steps to measure locomotion, and Training Impulse (TRIMP) to quantify the intensity and duration of PAs using heart rate. Plasma amyloid beta 42/40 ratio, phosphorylated tau 181, neurofilament light chain, and glial fibrillary acidic protein (GFAP) were measured. Cognition was assessed with the Consortium to Establish a Registry for Alzheimer's Disease word list learning and delayed recall, Trail Making Test Part A, and Wechsler Adult Intelligence Scale-version IV Digit Span Backward. We conducted multiple linear regressions controlling for age, sex, body mass index, and education.ResultsThere were no associations among steps or TRIMP with plasma biomarkers or cognition. Greater TRIMP was related to higher GFAP levels.ConclusionsPA was not associated with cognition or plasma biomarkers. However, greater intensity and duration of PAs were related to higher GFAP. Participants engaged very little in moderate to vigorous PA. Therefore, light PA may not exert a significant protective effect in preclinical AD. Future work with larger samples and longitudinal data is needed to elucidate further the potential impact of PA on AD progression in the preclinical stages.HighlightsLocomotion (average steps) was not associated with plasma biomarkers or cognition.Greater training load (training impulse) was related to higher glial fibrillary acidic protein levels in mutation carriers.Light physical activity may not suffice to exert a protective effect on Alzheimer's disease.
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Project description:Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer's disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairment and dementia) from the longitudinal multi-center observational ADNI cohort. Participants were on average 75 years of age (SD = 7.89), 40.8% were female, 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD-LB+), 395 (49.7%) had only AD pathology (AD+LB-), and 177 (22.3%) had both pathologies (AD+LB+). The AD+LB+ group showed worst baseline performance for most cognitive outcomes and compared to the AD+LB- group faster global cognitive decline and more cortical hypometabolism, particularly in posterior brain regions. Neuropathological examination (n = 61) showed high sensitivity (26/27, 96.3%) and specificity (27/28, 96.4%) of the SAA-test. We showed that co-existing LB-positivity exacerbates cognitive decline and cortical brain hypometabolism in AD. In vivo LB pathology detection could enhance prognostic evaluations in clinical practice and could have implications for clinical AD trial design.
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