Neurobiology of aging
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Neurobiology of aging · Apr 2017
ReviewClinical validity of medial temporal atrophy as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.
Research criteria for Alzheimer's disease recommend the use of biomarkers for diagnosis, but whether biomarkers improve the diagnosis in clinical routine has not been systematically assessed. The aim is to evaluate the evidence for use of medial temporal lobe atrophy (MTA) as a biomarker for Alzheimer's disease at the mild cognitive impairment stage in routine clinical practice, with an adapted version of the 5-phase oncology framework for biomarker development. A literature review on visual assessment of MTA and hippocampal volumetry was conducted with other biomarkers addressed in parallel reviews. ⋯ Phase 3 (early detection ability) is partly achieved: most evidence is derived from research cohorts or clinical populations with short follow-up, but validation in clinical mild cognitive impairment cohorts is required. In phase 4, only the practical feasibility has been addressed for visual rating of MTA. The rest of phase 4 and phase 5 have not yet been addressed.
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Neurobiology of aging · Mar 2017
Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study.
Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. ⋯ This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.
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Neurobiology of aging · Feb 2017
Genetic and functional analysis of TBK1 variants in Korean patients with sporadic amyotrophic lateral sclerosis.
The TANK-binding kinase 1 (TBK1) gene has recently been identified as a novel causative gene of amyotrophic lateral sclerosis (ALS). This study aims to determine the frequency and spectrum of TBK1 variants and their functional implications in Korean patients with sporadic ALS (sALS). TBK1 sequences were analyzed in 129 consecutive patients with sALS using either multigene panel or exome sequencing. ⋯ In contrast, the 3 other missense variants of uncertain significance showed normal mRNA expression and no abnormalities in protein function. Based on these findings, the frequency of pathogenic TBK1 variants in Korean sALS patients was estimated to be 0.8% (1/129). In conclusion, pathogenic variants in TBK1 are rare but could be responsible for sALS in a small number of Korean patients.
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Neurobiology of aging · Jan 2017
Clinical features of Chinese patients with Gerstmann-Sträussler-Scheinker identified by targeted next-generation sequencing.
Gerstmann-Sträussler-Scheinker (GSS) is an autosomal dominant neurodegenerative disease due to mutations within prion protein (PRNP) gene. Clinically, it is not easy to distinguish GSS from spinocerebellar ataxia (SCA), especially in the early stage of disease. We aimed to identify genetic mutations in 8 Chinese pedigrees with dominant ataxia but excluded dynamic mutations of SCA genes. ⋯ P102L mutation. The variable phenotypes among these GSS patients indicated other genetic or environmental factors might be involved in the phenotypic heterogeneity of GSS. Our findings also support the proposal that screening of PRNP mutations should be performed for the patients with dominant ataxia if dynamic mutations of SCA genes were excluded.
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Neurobiology of aging · Sep 2016
Attenuated anticorrelation between the default and dorsal attention networks with aging: evidence from task and rest.
Anticorrelation between the default and dorsal attention networks is a central feature of human functional brain organization. Hallmarks of aging include impaired default network modulation and declining medial temporal lobe (MTL) function. However, it remains unclear if this anticorrelation is preserved into older adulthood during task performance, or how this is related to the intrinsic architecture of the brain. ⋯ At rest, there was a robust double dissociation, with older adults showing a pattern of reduced within-network FC, but increased between-network FC, across both networks, relative to young adults. Moreover, older adults showed reduced intrinsic resting-state FC of the MTL with both networks suggesting a fractionation of the MTL memory system in healthy aging. These findings demonstrate age-related dedifferentiation among these competitive large-scale networks during both task and rest, consistent with the idea that age-related changes are associated with a breakdown in the intrinsic functional architecture within and among large-scale brain networks.