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  • 1
    Online Resource
    Online Resource
    Heightened effort discounting is a common feature of both apathy and fatigue
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-11-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-11-15)
    Abstract: Apathy and fatigue have distinct aetiologies, yet can manifest in phenotypically similar ways. In particular, each can give rise to diminished goal-directed behaviour, which is often cited as a key characteristic of both traits. An important issue therefore is whether currently available approaches are capable of distinguishing between them. Here, we examined the relationship between commonly administered inventories of apathy and fatigue, and a measure of goal-directed activity that assesses the motivation to engage in effortful behaviour. 103 healthy adults completed self-report inventories on apathy (the Dimensional Apathy Scale), and fatigue (the Multidimensional Fatigue Inventory, and/or Modified Fatigue Impact Scale). In addition, all participants performed an effort discounting task, in which they made choices about their willingness to engage in physically effortful activity. Importantly, self-report ratings of apathy and fatigue were strongly correlated, suggesting that these inventories were insensitive to the fundamental differences between the two traits. Furthermore, greater effort discounting was strongly associated with higher ratings across all inventories, suggesting that a common feature of both traits is a lower motivation to engage in effortful behaviour. These results have significant implications for the assessment of both apathy and fatigue, particularly in clinical groups in which they commonly co-exist.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-01287-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 2
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    Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-05-09)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-05-09)
    Abstract: Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a “visual tetanus”. Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-34749-w
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 3
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    Statins for extension of disability-free survival and primary prevention of cardiovascular events among older people: protocol for a randomised controlled trial in primary care (STAREE trial)
    BMJ ; 2023
    In:  BMJ Open Vol. 13, No. 4 ( 2023-04), p. e069915-
    Details
    In: BMJ Open, BMJ, Vol. 13, No. 4 ( 2023-04), p. e069915-
    Abstract: The world is undergoing a demographic transition to an older population. Preventive healthcare has reduced the burden of chronic illness at younger ages but there is limited evidence that these advances can improve health at older ages. Statins are one class of drug with the potential to prevent or delay the onset of several causes of incapacity in older age, particularly major cardiovascular disease (CVD). This paper presents the protocol for the STAtins in Reducing Events in the Elderly (STAREE) trial, a randomised double-blind placebo-controlled trial examining the effects of statins in community dwelling older people without CVD, diabetes or dementia. Methods and analysis We will conduct a double-blind, randomised placebo-controlled trial among people aged 70 years and over, recruited through Australian general practice and with no history of clinical CVD, diabetes or dementia. Participants will be randomly assigned to oral atorvastatin (40 mg daily) or matching placebo (1:1 ratio). The co-primary endpoints are disability-free survival defined as survival-free of dementia and persistent physical disability, and major cardiovascular events (cardiovascular death or non-fatal myocardial infarction or stroke). Secondary endpoints are all-cause death, dementia and other cognitive decline, persistent physical disability, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, heart failure, atrial fibrillation, fatal and non-fatal cancer, all-cause hospitalisation, need for permanent residential care and quality of life. Comparisons between assigned treatment arms will be on an intention-to-treat basis with each of the co-primary endpoints analysed separately in time-to-first-event analyses using Cox proportional hazards regression models. Ethics and dissemination STAREE will address uncertainties about the preventive effects of statins on a range of clinical outcomes important to older people. Institutional ethics approval has been obtained. All research outputs will be disseminated to general practitioner co-investigators and participants, published in peer-reviewed journals and presented at national and international conferences. Trial registration number NCT02099123 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/bmjopen-2022-069915
    DOI: 10.1136/bmjopen-2022-069915.supp1
    DOI: 10.1136/bmjopen-2022-069915.supp2
    DOI: 10.1136/bmjopen-2022-069915.supp3
    DOI: 10.1136/bmjopen-2022-069915.supp4
    DOI: 10.1136/bmjopen-2022-069915.supp5
    DOI: 10.1136/bmjopen-2022-069915.supp6
    DOI: 10.1136/bmjopen-2022-069915.supp7
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2599832-8
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  • 4
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Neurology Vol. 13 ( 2022-8-3)
    Details
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-8-3)
    Abstract: There is variability across individuals in cognitive aging. To investigate the associations of several modifiable factors with high and low cognitive performance. Methods Data came from 17,724 community-dwelling individuals aged 65–98 years. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed over up to seven years. Group-based multi-trajectory modeling identified distinct cognitive trajectories. Structural equation modeling examined the direct/indirect associations of social/behavioral factors and several chronic conditions with cognitive trajectories. Results Seven trajectory subgroups were identified. In the structural equation modeling we compared two subgroups-participants with the highest (14.2%) and lowest (4.1%) cognitive performance with the average subgroup. Lower education, never alcohol intake, and frailty directly predicted increased risk of low performance, and decreased likelihood of high performance. Hypertension (RR: 0.69, 95%CI: 0.60–0.80), obesity (RR: 0.84, 95%CI: 0.73–0.97), diabetes (RR: 0.69, 95%CI: 0.56–0.86) and depression (RR: 0.68, 95%CI: 0.54–0.85) only predicted lower likelihood of high cognitive performance, while dyslipidemia was only associated with low performance (RR: 1.30, 95%CI: 1.07–1.57). Living alone predicted increased risk of low cognitive performance and several comorbidities. Smoking did not predict cognitive trajectories but was associated with increased risk of diabetes, obesity and frailty. Findings were similar when examining the direct associations between modifiable risk factors and all seven cognitive subgroups. Conclusions Although several modifiable factors were associated with high performance, and reversely with low performance, this was not observed for obesity, hypertension and dyslipidemia. Further, health behaviors may affect cognitive function indirectly, via geriatric conditions. This indicates that strategies to promote healthy cognitive aging, may be distinct from those targeting dementia prevention.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    URL: Article
    URL: Article
    DOI: 10.3389/fneur.2022.950644
    DOI: 10.3389/fneur.2022.950644.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 5
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    A qualitative examination of apathy and physical activity in Huntington's and Parkinson's disease
    Future Medicine Ltd ; 2022
    In:  Neurodegenerative Disease Management Vol. 12, No. 3 ( 2022-06), p. 129-139
    Details
    In: Neurodegenerative Disease Management, Future Medicine Ltd, Vol. 12, No. 3 ( 2022-06), p. 129-139
    Abstract: Aim: In Huntington's disease (HD) and Parkinson's disease (PD), apathy is a frequently cited barrier to participation in physical activity. Current diagnostic criteria emphasize dissociable variants of apathy that differentially affect goal-directed behavior. How these dimensions present and affect physical activity in HD and PD is unknown. Methods: Using a qualitative approach, we examined the experience of apathy and its impact on physical activity in 20 people with early-manifest HD or idiopathic PD. Results: Two major themes emerged: the multidimensionality of apathy, including initiation or goal-identification difficulties, and the interplay of apathy and fatigue; and facilitators of physical activity, including routines, safe environments and education. Conclusion: Physical activity interventions tailored to apathy phenotypes may maximize participant engagement.
    Type of Medium: Online Resource
    ISSN: 1758-2024 , 1758-2032
    URL: Article
    DOI: 10.2217/nmt-2021-0047
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
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  • 6
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    Validation of newly derived polygenic risk scores for dementia in a prospective study of older individuals
    Wiley ; 2023
    In:  Alzheimer's & Dementia
    Details
    In: Alzheimer's & Dementia, Wiley
    Abstract: Recent genome‐wide association studies identified new dementia‐associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. Methods We used Cox models and area under the curve (AUC) to validate new PRSs (PRS‐83SNP, PRS‐SBayesR, and PRS‐CS) compared with an older PRS‐23SNP in 12,031 initially‐healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV) criteria. Results PRS‐83SNP, PRS‐SBayesR, and PRS‐CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [ APOE ] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23–1.47), 1.37 (1.25–1.50), and 1.42 (1.30–1.56), respectively. The AUC of a model containing conventional/non‐genetic factors and APOE was 74.7%. This was improved to 75.7% ( p  = 0.007), 76% ( p  = 0.004), and 76.1% ( p  = 0.003) with addition of PRS‐83SNP, PRS‐SBayesR, and PRS‐CS, respectively. The PRS‐23SNP did not improve AUC (74.7%, p  = 0.95). Conclusion New PRSs for dementia significantly improve risk‐prediction performance, but still account for less risk than APOE genotype overall.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Article
    DOI: 10.1002/alz.13113
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
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  • 7
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    Grip strength, gait speed, and trajectories of cognitive function in community‐dwelling older adults: A prospective study
    Wiley ; 2023
    In:  Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring Vol. 15, No. 1 ( 2023-01)
    Details
    In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Wiley, Vol. 15, No. 1 ( 2023-01)
    Abstract: This study investigated whether grip strength and gait speed predict cognitive aging trajectories and examined potential sex‐specific associations. Methods Community‐dwelling older adults ( n  = 19,114) were followed for up to 7 years, with regular assessment of global function, episodic memory, psychomotor speed, and executive function. Group‐based multi‐trajectory modeling identified joint cognitive trajectories. Multinomial logistic regression examined the association of grip strength and gait speed at baseline with cognitive trajectories. Results High performers (14.3%, n  = 2298) and low performers (4.0%, n  = 642) were compared to the average performers (21.8%, n  = 3492). Grip strength and gait speed were positively associated with high performance and negatively with low performance ( P ‐values  〈  0.01). The association between grip strength and high performance was stronger in women (interaction P   〈  0.001), while gait speed was a stronger predictor of low performance in men (interaction P   〈  0.05). Discussion Grip strength and gait speed are associated with cognitive trajectories in older age, but with sex differences. Highlights There is inter‐individual variability in late‐life cognitive trajectories. Grip strength and gait speed predicted cognitive trajectories in older age. However, sex‐specific associations were identified. In women, grip strength strongly predicted high, compared to average, trajectory. In men, gait speed was a stronger predictor of low cognitive performance trajectory.
    Type of Medium: Online Resource
    ISSN: 2352-8729 , 2352-8729
    URL: Issue
    URL: Article
    DOI: 10.1002/dad2.v15.1
    DOI: 10.1002/dad2.12388
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2832898-X
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  • 8
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    Multidimensional Apathy: The Utility of the Dimensional Apathy Scale in Huntington's Disease
    Wiley ; 2021
    In:  Movement Disorders Clinical Practice Vol. 8, No. 3 ( 2021-04), p. 361-370
    Details
    In: Movement Disorders Clinical Practice, Wiley, Vol. 8, No. 3 ( 2021-04), p. 361-370
    Abstract: Apathy is a disorder of motivation common to Huntington's disease (HD). Recent conceptual frameworks suggest that apathy is not unitary but consists of discrete subtypes (“dimensions”). Which of the proposed dimensions are preferentially affected in HD, and how these dimensions evolve with disease progression is unknown. Objectives The Dimensional Apathy Scale (DAS) separates apathy into Executive, Initiation and Emotional subscales. Using the DAS, we aimed to: 1) Determine the apathy subtypes prevalent in HD; 2) Compare the DAS against a unitary measure of apathy (Apathy Evaluation Scale, AES); 3) Assess the reliability of self‐ and observer‐ratings; and 4) Determine the relationship between the DAS, and disease burden, total functional capacity (TFC) and the AES. Method Fifty pre‐manifest, 51 manifest‐HD, 87 controls, and 50 HD‐observers completed the DAS, AES, and TFC. Results Manifest‐HD participants had the highest levels of apathy across all dimensions (30.4% on Executive subscale, 34.8% on Initiation subscale, and 15.2% on Emotional subscale), relative to pre‐manifest and control participants. Self‐ and observer‐ratings on the DAS did not differ. Hierarchical regressions across the entire gene‐expanded sample showed that scores on the Initiation subscale correlated with AES scores; higher Executive subscale scores were related to higher disease burden; and Emotional subscale scores with lower total functional capacity. Conclusions In this first study of the DAS in HD, manifest‐HD participants were more apathetic than pre‐manifest and control participants across all apathy subtypes. The DAS may be a useful tool for measuring different aspects of apathy in people with HD.
    Type of Medium: Online Resource
    ISSN: 2330-1619 , 2330-1619
    URL: Issue
    URL: Article
    DOI: 10.1002/mdc3.v8.3
    DOI: 10.1002/mdc3.13147
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2772809-2
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  • 9
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    Dissociable Motivational Deficits in Pre-manifest Huntington’s Disease
    Elsevier BV ; 2020
    In:  Cell Reports Medicine Vol. 1, No. 9 ( 2020-12), p. 100152-
    Details
    In: Cell Reports Medicine, Elsevier BV, Vol. 1, No. 9 ( 2020-12), p. 100152-
    Type of Medium: Online Resource
    ISSN: 2666-3791
    URL: Article
    DOI: 10.1016/j.xcrm.2020.100152
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 3019420-9
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  • 10
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    Associations of body habitus and its changes with incident dementia in older adults
    Wiley ; 2024
    In:  Journal of the American Geriatrics Society
    Details
    In: Journal of the American Geriatrics Society, Wiley
    Abstract: This study examined the associations of body mass index (BMI) and waist circumference (WC), as well as their short‐ and long‐term changes over time, with incident dementia in older individuals. Methods Data came from 18,837 community‐dwelling individuals aged 65+ years from Australia and the United States, who were relatively healthy without major cognitive impairment at enrolment. Anthropometric measures were prospectively assessed at baseline, as well as change and variability from baseline to year two (three time‐points). In a subgroup ( n = 11,176), self‐reported weight at age 18 and 70+ years was investigated. Dementia cases satisfied DSM‐IV criteria. Cox regression was used to examine the associations between anthropometric measures and incident risk of dementia. Results Compared to normal weight, an overweight (HR: 0.67, 95%CI: 0.57–0.79, p 〈 0.001) or obese BMI (HR: 0.73, 95%CI: 0.60–0.89, p = 0.002), or a larger WC (elevated, HR: 0.71, 95%CI: 0.58–0.86, p 〈 0.001; highly elevated, HR: 0.65, 95%CI: 0.55–0.78, p 〈 0.001; relative to low) at baseline was associated with lower dementia risk. In contrast, substantial increases in BMI ( 〉 5%) over 2 years after baseline were associated with higher dementia risk (HR: 1.49, 95% CI: 1.17–1.91, p = 0.001). Increased dementia risk was also seen with an underweight BMI at baseline and a 2‐year BMI decrease ( 〉 5%), but these associations appeared only in the first 4 years of follow‐up. Compared to normal weight at both age 18 and 70+ years, being obese at both times was associated with increased dementia risk (HR: 2.27, 95%CI: 1.22–4.24, p = 0.01), while obesity only at age 70+ years was associated with decreased risk (HR: 0.70, 95%CI: 0.51–0.95, p = 0.02). Conclusions Our findings suggest that long‐term obesity and weight gain in later life may be risk factors for dementia. Being underweight or having substantial weight loss in old age may be early markers of pre‐clinical dementia.
    Type of Medium: Online Resource
    ISSN: 0002-8614 , 1532-5415
    URL: Article
    DOI: 10.1111/jgs.18757
    Language: English
    Publisher: Wiley
    Publication Date: 2024
    detail.hit.zdb_id: 2040494-3
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