Neurobiology of aging
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Neurobiology of aging · Apr 2013
Age effect on the default mode network, inner thoughts, and cognitive abilities.
Age-related effects on the default mode network (DMN) connectivity as measured at rest using functional magnetic resonance imaging (fMRI) are now well described. Little is known however about the relationships between these changes and age-related effects on cognition or on the unconstrained thoughts which occur during the resting-state scan, called inner experience. Brain resting-state activity, inner experience, and cognitive ability measurements were obtained in 70 participants aged 19-80 years. ⋯ A significant effect of age was also found on cognitive abilities but not on inner experience. Finally, age-related changes in DMN connectivity were found to correlate with cognitive abilities, and more specifically with autobiographical memory performance. These findings provide new information to fuel the debate on the role of the brain default mode and more specifically on the effect of age-related changes in resting-state activity as measured with fMRI.
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Neurobiology of aging · Apr 2013
De novo FUS gene mutations are associated with juvenile-onset sporadic amyotrophic lateral sclerosis in China.
Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of motor neuron disease and occurs before 25 years of age. Only very few sporadic cases of juvenile-onset ALS have been reported. Rare SOD1 mutations and several FUS mutations have been identified in juvenile-onset ALS patients. ⋯ In the Chinese population, the frequency of FUS mutation in FALS is 11.4% (95% confidence interval [CI], 0.9%-22.0%), higher than the Japanese (10%; 95% CI, 0.7%-19.3%), and Caucasians (4.9%; 95% CI, 3.9%-6.0%). The frequency of FUS mutation in SALS patients is 1.5% (95% CI, 0.2%-2.9%), which is similar to Koreans (1.6%; 95% CI, 0%-3.2%), but higher than in Caucasians (0.6%; 95% CI, 0.4%-0.8%). Our findings suggest that de novo FUS mutations are associated with juvenile-onset SALS of Chinese origin and that this gene should be screened in ALS patients with a young age of onset, aggressive progression, and sporadic occurrence.
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Neurobiology of aging · Feb 2013
Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates.
We aimed to assess associations between clinical, imaging, pathologic, and genetic features and frontal lobe asymmetry in behavioral variant frontotemporal dementia (bvFTD). Volumes of the left and right dorsolateral, medial, and orbital frontal lobes were measured in 80 bvFTD subjects and subjects were classified into 3 groups according to the degree of asymmetry (asymmetric left, asymmetric right, symmetric) using cluster analysis. The majority of subjects were symmetric (65%), with 20% asymmetric left and 15% asymmetric right. ⋯ More widespread atrophy involving the parietal lobe was observed in the symmetric group. Genetic features differed across groups with symmetric frontal lobes associated with C9ORF72 and tau mutations, while asymmetric frontal lobes were associated with progranulin mutations. These findings therefore suggest that neuroanatomical patterns of frontal lobe atrophy in bvFTD are influenced by specific gene mutations.
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Neurobiology of aging · Jan 2013
Physical health and incident late-life depression: modification by cytokine genes.
Inflammatory cytokines have been implicated in the pathophysiology of depression, potentially underlying its association with worse physical health. Cytokine production is influenced by the transcriptional activity of several polymorphisms. We hypothesized that alleles related to higher proinflammatory and/or lower anti-inflammatory cytokine production would strengthen the association between physical disorders and late-life depression. ⋯ The associations between physical disorders and incident depression were significant in the presence of 2 alleles related to higher proinflammatory cytokine production (tumor necrosis factor-α -850T and IL-8 -251A), and 1 allele related to lower anti-inflammatory cytokine production (IL-4 +33C). Significant gene-environment interactions, independent of all covariates, were found for total number of risk alleles on both pro- and anti-inflammatory cytokine genes in addition to the above 3 individual single nucleotide polymorphisms. The present findings support cytokine-mediated inflammatory pathways underlying at least some of the well-recognized association between worse physical health and late-life depression, and provide novel evidence of a genetic basis for this.
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Neurobiology of aging · Dec 2012
Case Reports Multicenter StudyVAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient.
Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97 families), and 765 control subjects of Dutch descent for mutations in vesicle-associated membrane protein B (VAPB). ⋯ This p. V234I mutation was absent in control subjects, located in a region with high evolutionary conservation, and predicted to have damaging effects. Taken together, these findings provide additional evidence for an oligogenic basis of ALS.