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Background The rising prevalence of dementia necessitates identifying early neurobiological markers of dementia risk. Reduced cerebral white matter volume and flattening of the slope of the electrophysiological 1/f spectral power distribution provide neurobiological markers of brain ageing alongside cognitive decline. However, their association with modifiable dementia risk remains to be understood. Methods A cross-sectional sample of 98 healthy older adults (79 females, mean age = 65.44) underwent structural magnetic resonance imaging (sMRI), resting-state electroencephalography (EEG), cognitive assessments and dementia risk scoring using the CogDrisk framework. Univariate and multivariate linear regression models were conducted to investigate the relationships between modifiable dementia risk and sMRI brain volumes, the exponent of EEG 1/f spectral power, and cognition, whilst controlling for non-modifiable factors. Results Smaller global white matter volume (F (1,87) = 6.884, R 2 = 0.073, P  = .010), and not grey (F (1,87) = 0.540, R 2 = 0.006, P  = .468) or ventricle volume (F (1,87) = 0.087, R 2 = 0.001, P  = .769), was associated with higher modifiable dementia risk. A lower exponent, reflecting a flatter 1/f spectral power distribution, was associated with higher dementia risk at frontal (F (1,92) = 4.096, R 2 = 0.043, P  = .046) but not temporal regions. No significant associations were found between cognitive performance and dementia risk. In multivariate analyses, both white matter volume and the exponent of the 1/f spectral power distribution independently associated with dementia risk. Conclusions Structural and functional neurobiological markers of early brain ageing, but not cognitive function, are independently associated with modifiable dementia risk in healthy older adults. [ABSTRACT FROM AUTHOR]

For older people, physical inactivity increases fall risk as well as other preventable health conditions. Despite the well-documented benefits of physical activity, uptake and adherence continue to challenge efforts aimed at increasing physical activity and reducing falls. Nested within a randomized controlled trial, this study reports on the factors influencing the physical activity behavior of people, aged between 70 and 90 years, engaged in StandingTall, a home-based balance exercise program proven to reduce falls in the community. The perception of aging, physical activity in older age, and the delivery of exercise were identified as major themes, with the perception of aging an overarching theme influencing both preferences for physical activity in older age and exercise delivery. Findings demonstrate the importance of considering the role of aging, the influence aging has on physical activity and exercise behavior, and how aging influences the delivery and design of exercise programs including falls prevention activities for older people. [ABSTRACT FROM AUTHOR]

Apathy is one of the most common neuropsychiatric features of Huntington's disease. A hallmark of apathy is diminished goal-directed behaviour, which is characterized by a lower motivation to engage in cognitively or physically effortful actions. However, it remains unclear whether this reduction in goal-directed behaviour is driven primarily by a motivational deficit and/or is secondary to the progressive cognitive and physical deficits that accompany more advanced disease. We addressed this question by testing 17 individuals with manifest Huntington's disease and 22 age-matched controls on an effort-based decision-making paradigm. Participants were first trained on separate cognitively and physically effortful tasks and provided explicit feedback about their performance. Next, they chose on separate trials how much effort they were willing to exert in each domain in return for varying reward. At the conclusion of the experiment, participants were asked to rate their subjective perception of task load. In the cognitive task, the Huntington's disease group were more averse to cognitive effort than controls. Although the Huntington's disease group were more impaired than controls on the task itself, their greater aversion to cognitive effort persisted even after controlling for task performance. This suggests that the lower levels of cognitive motivation in the Huntington's disease group relative to controls was most likely driven by a primary motivational deficit. In contrast, both groups expressed a similar preference for physical effort. Importantly, the similar levels of physical motivation across both groups occurred even though participants with Huntington's disease performed objectively worse than controls on the physical effort task, and were aware of their performance through explicit feedback on each trial. This indicates that the seemingly preserved level of physical motivation in Huntington's disease was driven by a willingness to engage in physically effortful actions despite a reduced capacity to do so. Finally, the Huntington's disease group provided higher ratings of subjective task demand than controls for the cognitive (but not physical) effort task and when assessing the mental (but not the physical) load of each task. Together, these results revealed a dissociation in cognitive and physical motivation deficits between Huntington's disease and controls, which were accompanied by differences in how effort was subjectively perceived by the two groups. This highlights that motivation is the final manifestation of a complex set of mechanisms involved in effort processing, which are separable across different domains of behaviour. These findings have important clinical implications for the day-to-day management of apathy in Huntington's disease. [ABSTRACT FROM AUTHOR]

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants. IMPORTANCE Despite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant’s host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1. [ABSTRACT FROM AUTHOR]

Habits play an important role in physical activity (PA) engagement; however, these associations in older people are not well understood. The present study aimed to investigate the relationship between engagement in types of PA and their automaticity in older people, using an observational, cross-sectional design. Current hours engaged in planned exercise (excluding walking), planned walking, and incidental activities and the automaticity of those PA behaviors were measured in 127 community-dwelling Australians aged 65 years and older via an online questionnaire. After controlling for demographic and health factors (age, gender, education level, body mass index, history of falls, and anxiety and depression symptoms), higher automaticity scores were associated with more hours undertaking planned walking and incidental activity but not planned exercise. Although preliminary, these findings indicate that the role of habit in maintaining PA in older people may, therefore, differ depending on the type of activity. [ABSTRACT FROM AUTHOR]

Background: Speech and language impairments are well-established in individuals with amyotrophic lateral sclerosis (ALS). However, knowledge about particular aspects of social communication and everyday conversational abilities is limited. Aims: To investigate self- and informant-report ratings of social communicative abilities in ALS participants and matched healthy controls. Methods & Procedures: Thirty-two participants with ALS and 24 controls completed the La Trobe Communication Questionnaire (LCQ). Participants nominated a close other to provide an informant report on the LCQ. Demographic and clinical information was also collected. Outcomes & Results: Informant ratings indicated greater difficulties in conversational initiation, effectiveness and partner sensitivity for ALS participants compared with controls. ALS participants did not rate their social communicative abilities as poorer than controls and self-reports only differed from informant ratings in the control group. LCQ scores were not significantly correlated with clinical/functional variables. Conclusions & Implications: Social communication can be reduced in ALS and individuals may lack insight into these difficulties. In order to understand and provide targeted interventions for such difficulties, clinical speech and language assessment should incorporate social communication assessment, including both a self- and informant-report format.

Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single‐ and paired‐pulse TMS measurements were collected before and after a 20 min bout of high‐intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre‐ to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age‐dependent decline in cortical plasticity and indicate that a preceding bout of high‐intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. Key points: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown.Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high‐intensity interval exercise and again after a plasticity‐inducing protocol, intermittent theta burst stimulation.In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition.Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults.Our findings demonstrate an age‐dependent decline in exercise‐enhanced cortical plasticity and indicate that a preceding bout of high‐intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. [ABSTRACT FROM AUTHOR]