Neurobiology of aging
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Neurobiology of aging · Apr 2019
Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study.
In genetic frontotemporal dementia, cross-sectional studies have identified profiles of presymptomatic neuroanatomical loss for C9orf72 repeat expansion, MAPT, and GRN mutations. In this study, we characterize longitudinal gray matter (GM) and white matter (WM) brain changes in presymptomatic frontotemporal dementia. We included healthy carriers of C9orf72 repeat expansion (n = 12), MAPT (n = 15), GRN (n = 33) mutations, and related noncarriers (n = 53), that underwent magnetic resonance imaging at baseline and 2-year follow-up. ⋯ MAPT mutation carriers showed emerging GM temporal lobe changes and longitudinal WM degeneration of the uncinate fasciculus. GRN mutation carriers did not show presymptomatic neurodegeneration. This study shows distinct presymptomatic cross-sectional and longitudinal patterns of GM and WM changes across C9orf72 repeat expansion, MAPT, and GRN mutation carriers compared with noncarriers.
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Neurobiology of aging · Jan 2019
Neurometabolites and associations with cognitive deficits in mild cognitive impairment: a magnetic resonance spectroscopy study at 7 Tesla.
The levels of several brain metabolites were investigated in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) in 13 healthy controls (HC) and 13 patients with mild cognitive impairment (MCI) using single-voxel magnetic resonance spectroscopy at 7T. Levels of γ-aminobutyric acid (GABA), glutamate (Glu), glutathione (GSH), N-acetylaspartylglutamate (NAAG), N-acetylaspartate (NAA), and myo-inositol (mI) were quantified relative to total creatine (tCr). The effect of diagnosis on metabolite levels, and relationships between metabolite levels and memory and executive function, correcting for age, were investigated. ⋯ Worse verbal fluency performance was correlated with lower GSH/tCr (PCC). In summary, MCI is associated with decreased GABA and Glu, most consistently in the PCC. Further studies in larger patient samples should be undertaken to determine the utility of 7T magnetic resonance spectroscopy in detecting MCI-related neurochemical changes.
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Neurobiology of aging · Dec 2018
Circulating vitamin E levels and Alzheimer's disease: a Mendelian randomization study.
Alzheimer's disease (AD) is the leading cause of dementia in older adults. It is more than 50 years since vitamin E was recognized as critical for optimal neurological health. Clinical studies have yielded inconsistent findings on the effect of vitamin E on AD risk. ⋯ Mendelian randomization-Egger intercept test showed no significant pleiotropy (β = -0.113; p = 0.296). Inverse-variance weighted (odds ratio = 0.96, 95% confidence interval: 0.47-1.94, p = 0.936) and weighted median analyses (odds ratio = 1.13, 95% confidence interval: 0.35-3.69, p = 0.836) showed no significant association between vitamin E and AD. Together with previous literature, this suggests that vitamin E supplementation may not forestall AD in the general population.
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Neurobiology of aging · Oct 2018
Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis.
Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS)-related genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. ⋯ The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (∼10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population.
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Neurobiology of aging · Sep 2018
Independent effects of age and levodopa on reversal learning in healthy volunteers.
The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson's disease. It posits that effects of dopaminergic therapy on cognition in Parkinson's disease depend on baseline dopamine levels in brain regions that support different functions. Although functions performed by more severely dopamine-depleted brain regions improve with medication, those associated with less dopamine deficient areas are actually worsened. ⋯ Levodopa worsened stimulus-reward learning relative to placebo to the same extent in both groups, irrespective of differences in baseline performance and expected dopamine levels. When order effects were eliminated, levodopa induced response shifts after reward more often than placebo. Our results reveal independent deleterious effects of age group and exogenous dopamine on reward learning, suggesting a more complex scenario than predicted by the dopamine overdose hypothesis.