After a median follow-up of 4.7 years, there were 1.6 more deaths per 1000 person-years among healthy older adults who were randomly assigned to receive aspirin than among those who received placebo. ...Cancer-related death accounted for much of the excess mortality.
Pregnancy and the early postpartum period alter the structure of the brain; particularly in regions related to parental care. However, the enduring effects of this period on human brain structure and ...cognition in late life is unknown. Here we use magnetic resonance imaging to examine differences in cortical thickness related to parenthood in late life, for both sexes. In 235 healthy older women, we find a positive relationship between parity (number of children parented) and memory performance in mothers. Parity was also associated with differences in cortical thickness in women in the parahippocampus, precuneus, cuneus and pericalcarine sulcus. We also compared non-parents to parents of one child, in a sub-sample of older women (N = 45) and men (N = 35). For females, six regions differed in cortical thickness between parents and non-parents; these regions were consistent with those seen earlier in life in previous studies. For males, five regions differed in cortical thickness between parents and non-parents. We are first to reveal parenthood-related brain differences in late-life; our results are consistent with previously identified areas that are altered during pregnancy and the postpartum period. This study provides preliminary evidence to suggest that neural changes associated with early stages of parenthood persist into older age, and for women, may be related to marginally better cognitive outcomes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Individual differences in haemoglobin significantly impact measures of functional connectivity in the elderly.•Despite no cognitive differences, connectivity-cognition relationships differed between ...low- and high-haemoglobin groups.•The influence of haemoglobin on functional connectivity differs between men and women.
Resting-state connectivity measures the temporal coherence of the spontaneous neural activity of spatially distinct regions, and is commonly measured using BOLD-fMRI. The BOLD response follows neuronal activity, when changes in the relative concentration of oxygenated and deoxygenated haemoglobin cause fluctuations in the MRI T2* signal. Since the BOLD signal detects changes in relative concentrations of oxy/deoxy-haemoglobin, individual differences in haemoglobin levels may influence the BOLD signal-to-noise ratio in a manner independent of the degree of neural activity. In this study, we examined whether group differences in haemoglobin may confound measures of functional connectivity. We investigated whether relationships between measures of functional connectivity and cognitive performance could be influenced by individual variability in haemoglobin. Finally, we mapped the neuroanatomical distribution of the influence of haemoglobin on functional connectivity to determine where group differences in functional connectivity are manifest.
In a cohort of 518 healthy elderly subjects (259 men), each sex group was median-split into two groups with high and low haemoglobin concentration. Significant differences were obtained in functional connectivity between the high and low haemoglobin groups for both men and women (Cohen's d 0.17 and 0.03 for men and women respectively). The haemoglobin connectome in males showed a widespread systematic increase in functional connectivity correlation values, whilst the female connectome showed predominantly parietal and subcortical increases and temporo-parietal decreases. Despite the haemoglobin groups having no differences in cognitive measures, significant differences in the linear relationships between cognitive performance and functional connectivity were obtained for all 5 cognitive tests in males, and 4 out of 5 tests in females.
Our findings confirm that individual variability in haemoglobin levels that give rise to group differences are an important confounding variable in BOLD-fMRI-based studies of functional connectivity. Controlling for haemoglobin variability as a potentially confounding variable is crucial to ensure the reproducibility of human brain connectome studies, especially in studies that compare groups of individuals, compare sexes, or examine connectivity-cognition relationships.
OBJECTIVE:To elucidate the neuropathology in cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS), a novel cerebellar ataxia comprised of the triad of cerebellar ...impairment, bilateral vestibular hypofunction, and a peripheral sensory deficit.
METHOD:Brain and spinal neuropathology in 2 patients with CANVAS, together with brain and otopathology in another patient with CANVAS, were examined postmortem.
RESULTS:Spinal cord pathology demonstrated a marked dorsal root ganglionopathy with secondary tract degeneration. Cerebellar pathology showed loss of Purkinje cells, predominantly in the vermis.
CONCLUSION:The likely underlying sensory pathology in CANVAS is loss of neurons from the dorsal root and V, VII, and VIII cranial nerve ganglia—in other words, it is a “neuronopathy” rather than a “neuropathy.” Clinically, CANVAS is a differential diagnosis for both spinocerebellar ataxia type 3 (or Machado-Joseph disease) and Friedreich ataxia. In addition, there are 6 sets of sibling pairs, implying that CANVAS is likely to be a late-onset recessive or autosomal dominant with reduced penetrance disorder, and identification of the culprit gene is currently a target of investigation.
The dominantly-inherited ataxias characterised by expanded polyglutamine tracts-spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA ...8-have all been shown to result in various degrees of cognitive impairment. We survey the literature on the cognitive consequences of each disorder, attempting correlation with their published neuropathological, magnetic resonance imaging (MRI) and clinical features. We suggest several psychometric instruments for assessment of executive function, whose results are unlikely to be confounded by visual, articulatory or upper limb motor difficulties. Finally, and with acknowledgement of the inadequacies of the literature to date, we advance a tentative classification of these disorders into three groups, based on the reported severity of their cognitive impairments, and correlated with their neuropathological topography and MRI findings: group 1-SCAs 6 and 8-mild dysexecutive syndrome based on disruption of cerebello-cortical circuitry; group 2-SCAs 1, 2, 3, and 7-more extensive deficits based largely on disruption of striatocortical in addition to cerebello-cerebral circuitry; and group 3-SCA 17 and DRPLA-in which cognitive impairment severe enough to cause a dementia syndrome is a frequent feature.
Late-life depression is common and often inadequately managed using existing therapies. Depression is also associated with increased markers of inflammation, suggesting a potential role for ...anti-inflammatory agents. ASPREE-D is a sub-study of ASPREE, a large multi-centre, population-based, double-blind, placebo-controlled trial of aspirin vs placebo in older Australian and American adults (median follow-up: 4.7 years) of whom 1879 were depressed at baseline. Participants were given 100 mg daily dose of aspirin or placebo. Depressive symptoms were assessed annually using the validated, self-rated short version of the Center for Epidemiological Studies Depression scale. There was a significant increase in depressive scores (0.6; 95% CI 0.2 to 0.9; χ
(1) = 10.37; p = 0.001) and a decreased score in the mental health component of a quality of life scale (-0.7; 95% CI -1.4 to -0.1; χ
(1) = 4.74; p = 0.029) in the aspirin group compared to the placebo group. These effects were greater in the first year of follow-up and persisted throughout the study, albeit with small to very small effect sizes. This study failed to demonstrate any benefit of aspirin in the long-term course of depression in this community-dwelling sample of older adults over a 5-year period, and identified an adverse effect of aspirin in the course of depression in those with pre-existing depressive symptoms.
We aimed to provide proof-of-principle evidence that intensive home-based speech treatment can improve dysarthria in complex multisystemic degenerative ataxias, exemplified by autosomal recessive ...spastic ataxia Charlevoix-Saguenay (ARSACS). Feasibility and piloting efficacy of speech training specifically tailored to cerebellar dysarthria was examined through a 4-week program in seven patients with rater-blinded assessment of intelligibility (primary outcome) and naturalness and acoustic measures of speech (secondary outcomes) performed 4 weeks before, immediately prior to, and directly after training (intraindividual control design). Speech intelligibility and naturalness improved post treatment. This provides piloting evidence that ataxia-tailored speech treatment might be effective in degenerative cerebellar disease.
Background There is evidence for a significant excess of kinetic upper limb tremor in non-FXTAS female FMR1 premutation carriers. The present study explores the possibility that this tremor is ...associated with various other features reminiscent of those occurring in syndromic FXTAS. Sample/methods This study analyzed the data from an Australian cohort of 48 asymptomatic premutation women. We utilized spiral drawings from CRST, representing action tremor; the CRST total tremor; and ICARS- kinetic tremors/cerebellar ataxia scales. Cognitive tests (involving executive functioning) included SDMT, TMT, two subtests of the WAIS-III: MR and Similarities. Spearman Rank correlations assessed the relationships between the above measures, and the Chi-square tested hypothesis about the association between the white matter hyperintensities ( wmhs ) in the splenium of corpus callosum assessed from MR images and spiral drawings scores. Results The spiral drawing scores were significantly correlated with all three non-verbal cognitive test scores, and with the CRST scores; the latter correlated with all four cognitive test measures. Similarities (verbal) scores correlated with CRST, ICARS, and with the remaining cognitive scores. Ordered spiral scores’ categories were significantly associated with the degree of splenium involvement. Conclusion This study showed that, in non-FXTAS premutation female carriers, sub-symptomatic forms of kinetic tremor were associated with a broader motor, and cognitive (especially executive) dysfunction.
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