Associations between physical activity, sedentary behaviour and cognitive domain performance of people living with mild cognitive impairment in the community.

INTRODUCTION: Physical activity is known to positively influence cognitive performance. For adults with mild cognitive impairment (MCI), the relationship between physical activity levels and cognitive performance is unknown. This cross-sectional study aimed to determine if cognitive performance [as measured by the Montreal Cognitive Assessment (MoCA)] of people living in the community with MCI is associated with their physical activity levels or sedentary behaviour. METHODS: ActivPAL™ accelerometers were used to objectively measure physical activity and sedentary behaviour for seven full days. Cognitive performance was measured using the MoCA. CONSUMER AND COMMUNITY INVOLVEMENT: No involvement other than as research participants RESULTS: Eighty-two participants from the Balance on the Brain randomised controlled trial were included. Most participants were retired (88%), with 33 (40%) reporting a fall in the last year. The median MoCA score was 24 (IQR 22-26). Participants achieved a mean of 6296 (±2420) steps per day and were sedentary for 10.6 (±2) hours per day. The only physical activity outcomes that had a fair, positive correlation were moderate- to vigorous-intensity physical activity measures of total stepping time and total number of steps (with a cadence of ≥100 steps/min) with the orientation MoCA domain score (r(82) = 0.36, p ≤ 0.001 and r(82) = 0.37, p ≤ 0.001, respectively). Higher total sedentary time had a weak, positive correlation with better visuospatial/executive performance (r(82) = 0.23, p = 0.041). The orientation outcomes remained significant when analysed in an adjusted logistic regression model. CONCLUSION: This study found that performance in the MoCA orientation domain had a fair-positive correlation with moderate-intensity physical activity (i.e., stepping time and step count with a cadence of ≥100 steps/min) as measured by a thigh-worn accelerometer for community-dwelling older adults with MCI. When considering the relationship between cognitive domains and sedentary behaviour, consideration may be needed regarding whether cognitive enhancing activities (such as crosswords and other brain games) are being performed, which may confound this relationship. Further investigation is required to confirm these results.

Linking self-perceived cognitive functioning questionnaires using item response theory: The subjective cognitive decline initiative.

OBJECTIVE: Self-perceived cognitive functioning, considered highly relevant in the context of aging and dementia, is assessed in numerous ways-hindering the comparison of findings across studies and settings. Therefore, the present study aimed to link item-level self-report questionnaire data from international aging studies. METHOD: We harmonized secondary data from 24 studies and 40 different questionnaires with item response theory (IRT) techniques using a graded response model with a Bayesian estimator. We compared item information curves to identify items with high measurement precision at different levels of the self-perceived cognitive functioning latent trait. Data from 53,030 neuropsychologically intact older adults were included, from 13 English language and 11 non-English (or mixed) language studies. RESULTS: We successfully linked all questionnaires and demonstrated that a single-factor structure was reasonable for the latent trait. Items that made the greatest contribution to measurement precision (i.e., "top items") assessed general and specific memory problems and aspects of executive functioning, attention, language, calculation, and visuospatial skills. These top items originated from distinct questionnaires and varied in format, range, time frames, response options, and whether they captured ability and/or change. CONCLUSIONS: This was the first study to calibrate self-perceived cognitive functioning data of geographically diverse older adults. The resulting item scores are on the same metric, facilitating joint or pooled analyses across international studies. Results may lead to the development of new self-perceived cognitive functioning questionnaires guided by psychometric properties, content, and other important features of items in our item bank. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Physical Activity for Cognitive Health: A Model for Intervention Design for People Experiencing Cognitive Concerns and Symptoms of Depression or Anxiety.

BACKGROUND: People experiencing cognitive concerns and symptoms of depression or anxiety are at risk for Alzheimer's disease and dementia. We know physical activity can benefit cognition but understanding how to best support engagement is an ongoing challenge. Evidence-based conceptual models of factors underpinning physical activity engagement in target populations can inform intervention tailoring to address this challenge. OBJECTIVE: This study (part of a pragmatic physical activity implementation trial) aimed to develop a specified model of physical activity engagement in people experiencing depressive or anxiety symptoms and cognitive concerns, to enable optimized dementia risk reduction intervention tailoring. METHODS: We employed a qualitative design, triangulating data from three sources: semi-structured individual interviews with people experiencing cognitive concerns and mild to moderate depressive or anxiety symptoms; review of published evidence; and the Capability, Opportunity and Motivation system of behavior, an existing behavioral science model. Findings were integrated to develop a contextualized model of mechanisms of action for optimizing engagement. RESULTS: Twenty-one participants were interviewed, and 24 relevant papers included. Convergent and complementary themes extended understanding of intervention needs. Findings highlighted emotional regulation, capacities to enact intentions despite barriers, and confidence in existing skills as areas of population-specific need that have not previously been emphasized. The final model provides specificity, directionality, and linked approaches for intervention tailoring. CONCLUSION: This study demonstrated that people experiencing cognitive concerns and symptoms of depression or anxiety require different interventions to improve physical activity engagement. This novel model can enable more precise intervention tailoring, and, ultimately, benefits for a key at-risk population.

Examination of the Feasibility, Acceptability, and Efficacy of the Online Personalised Training in Memory Strategies for Everyday Program for Older Adults: Single-Arm Pre-Post Trial.

BACKGROUND: Memory strategy training for older adults helps maintain and improve cognitive health but is traditionally offered face-to-face, which is resource intensive, limits accessibility, and is challenging during a pandemic. Web-based interventions, such as the Online Personalised Training in Memory Strategies for Everyday (OPTIMiSE) program, may overcome such barriers. OBJECTIVE: We report on OPTIMiSE's feasibility, acceptability, and efficacy. METHODS: Australians aged ≥60 years reporting subjective cognitive decline participated in this single-arm pre-post web-based intervention. OPTIMiSE is a 6-module web-based program offered over 8-weeks with a 3-month booster. It has a problem-solving approach to memory issues, focusing on psychoeducation about memory and aging, knowledge and practice of compensatory memory strategies, and personalized content related to individual priorities. We examined the feasibility (recruitment, attrition, and data collection), acceptability (recommendation to others, suggestions for improvement, and withdrawal reasons), and efficacy (change in goal satisfaction, strategy knowledge and use, self-reported memory, memory satisfaction and knowledge, and mood; thematic content analysis of the most significant change; and the application of knowledge and strategies in daily life) of OPTIMiSE. RESULTS: OPTIMiSE was feasible, demonstrated by strong interest (633 individuals screened), a satisfactory level of attrition (158/312, 50.6%), and minimal missing data from those completing the intervention. It was acceptable, with 97.4% (150/154) of participants agreeing they would recommend OPTIMiSE, the main suggestion for improvement being more time to complete modules, and withdrawal reasons similar to those in in-person interventions. OPTIMiSE was also efficacious, with linear mixed-effects analyses revealing improvements, of moderate to large effect sizes, across all primary outcomes (all P<.001): memory goal satisfaction (Cohen d after course=1.24; Cohen d at 3-month booster=1.64), strategy knowledge (Cohen d after course=0.67; Cohen d at 3-month booster=0.72) and use (Cohen d after course=0.79; Cohen d at 3-month booster=0.90), self-reported memory (Cohen d after course=0.80; Cohen d at 3-month booster=0.83), memory satisfaction (Cohen d after course=1.25; Cohen d at 3-month booster=1.29) and knowledge (Cohen d after course=0.96; Cohen d at 3-month booster=0.26), and mood (Cohen d after course=-0.35; nonsignificant Cohen d at booster). Furthermore, the most significant changes reported by participants (strategy use, improvements in daily life, reduced concern about memory, confidence and self-efficacy, and sharing and shame busting with others) reflected the course objectives and were consistent with themes arising from previous in-person interventions. At the 3-month booster, many participants reported continued implementation of knowledge and strategies in their daily lives. CONCLUSIONS: This feasible, acceptable, and efficacious web-based program has the potential to enable access to evidence-based memory interventions for older adults worldwide. Notably, the changes in knowledge, beliefs, and strategy use continued beyond the initial program. This is particularly important for supporting the growing number of older adults living with cognitive concerns. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000979954; https://tinyurl.com/34cdantv. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3233/ADR-200251.

Factors Influencing Long-Term Physical Activity Maintenance: A Qualitative Evaluation of a Physical Activity Program for Inactive Older Adults at Risk of Cognitive Decline: The INDIGO Follow-Up Study.

BACKGROUND: Physical inactivity is a modifiable risk factor for dementia, but there remains a research translation gap in effective physical activity (PA) implementation, particularly in the longer-term. The INDIGO trial investigated the effectiveness of a six-month PA intervention for inactive older adults at risk of cognitive decline with subjective cognitive decline or mild cognitive impairment. OBJECTIVE: This follow-up study aimed to collect feedback from INDIGO participants about their experience of involvement in the trial, including barriers and enablers to longer-term maintenance of PA. METHODS: A qualitative study using semi-structured individual interviews was conducted and transcripts analyzed thematically. All INDIGO trial completers were invited, with 29 participating (follow-up period 27-66 months post-baseline). RESULTS: At long-term follow-up, participants described INDIGO trial participation as beneficial. The theme of "Motivation" (subthemes: structure and accountability, knowledge and expected benefits, preferences and motivation, tools) followed by "Situation" (subthemes: environment and time, social aspects, aging and physical health) appeared to be critical to PA "Action". Most participants had a positive view of goal-setting and peer mentoring/support, but there was some polarization of opinion. Key factors to longer-term "Maintenance" of PA were self-efficacy and perceived benefits, habit formation, and for some participants, enjoyment. CONCLUSION: PA interventions for older adults at risk of cognitive decline should include behavior change techniques tailored to the individual. Effective techniques should focus on "Motivation" (particularly structure and accountability) and "Situation" factors relevant to individuals with the aim of developing self-efficacy, habit formation, and enjoyment to increase the likelihood of longer-term PA maintenance.

Behavioral Activation in Nursing Homes to Treat Depression (BAN-Dep): Results From a Clustered, Randomized, Single-Blinded, Controlled Clinical Trial.

OBJECTIVES: To determine if behavioral activation (BA) delivered by trained staff decreases prevalence of clinically significant symptoms of depression among older adults living in residential aged care facilities (RACFs). METHODS: Clustered, randomized, single-blinded, controlled trial of BA for adults aged over 60 years living permanently in a RACF with symptoms of depression (Patient Health Questionnaire, PHQ-9 ≥ 5). BA was delivered over 8-12 weeks using a structured workbook. The proportion of residents with PHQ-9 ≥ 10 at weeks 12, 26, and 52, as well as anxiety symptoms (GAD-7), physical (PCS), and mental (MCS) quality of life, loneliness, and loss to follow-up were main outcomes of interest RESULTS: We recruited 54 RACFs (26 intervention) and 188 of their residents (89 intervention). Participants were aged 61-100 years and 132 (70.2%) were women. PHQ-9 ≥ 10 interacted with BA at week 12 (OR = 0.34, 95%CI = 0.11-1.07), but differences between the groups were not statistically significant at any time-point. GAD-7 ≥ 10 interacted with BA at week 26 (OR = 0.12, 95%CI = 0.02-0.58), but not at any other time-point. Overall, the intervention had no effect on the scores of the PHQ-9, GAD-7, PCS, MCS, and loneliness scale. Loss to follow-up was similar between groups. Adherence to all stages of the intervention was poor (36.2%). CONCLUSIONS: Disruption by the COVID-19 pandemic and staffing issues in RACFs undermined recruitment and adherence. In such a context, a BA program delivered by RACF staff was not associated with better mental health outcomes for residents over 52 weeks.

Balance on the Brain: a randomised controlled trial evaluating the effect of a multimodal exercise programme on physical performance, falls, quality of life and cognition for people with mild cognitive impairment-study protocol.

INTRODUCTION: Exercise and physical activity have been shown to improve cognition for people living with mild cognitive impairment (MCI). There is strong evidence for the benefits of aerobic exercise and medium evidence for participating in regular strength training for people with MCI. However, people living with MCI fall two times as often as those without cognitive impairment and the evidence is currently unknown as to whether balance training for people with MCI is beneficial, as has been demonstrated for older people without cognitive impairment. The aim of this study is to determine whether a balance-focused multimodal exercise intervention improves balance and reduces falls for people with MCI, compared with a control group receiving usual care. METHODS AND ANALYSIS: This single blind randomised controlled trial (Balance on the Brain) will be offered to 396 people with MCI living in the community. The multimodal exercise intervention consists of two balance programmes and a walking programme to be delivered by physiotherapists over a 6-month intervention period. All participants will be followed up over 12 months (for the intervention group, this involves 6-month intervention and 6-month maintenance). The primary outcomes are (1) balance performance and (2) rate of falls. Physical performance, levels of physical activity and sedentary behaviour, quality of life and cognition are secondary outcomes. A health economic analysis will be undertaken to evaluate the cost-effectiveness of the intervention compared with usual care. ETHICS AND DISSEMINATION: Ethics approval has been received from the South Metropolitan Health Service Human Research Ethics Committee (HREC), Curtin University HREC and the Western Australia Department of Health HREC; and approval has been received to obtain data for health costings from Services Australia. The results will be disseminated through peer-review publications, conference presentations and online platforms. TRIAL REGISTRATION NUMBER: ACTRN12620001037998; Australian New Zealand Clinical Trials Registry (ANZCTR).

Effects of a physical activity intervention on brain atrophy in older adults at risk of dementia: a randomized controlled trial.

Lack of physical activity is a risk factor for dementia, however, the utility of interventional physical activity programs as a protective measure against brain atrophy and cognitive decline is uncertain. Here we present the effect of a randomized controlled trial of a 24-month physical activity intervention on global and regional brain atrophy as characterized by longitudinal voxel-based morphometry with T1-weighted MRI images. The study sample consisted of 98 participants at risk of dementia, with mild cognitive impairment or subjective memory complaints, and having at least one vascular risk factor for dementia, randomized into an exercise group and a control group. Between 0 and 24 months, there was no significant difference detected between groups in the rate of change in global, or regional brain volumes.

The Support Person's Preferences and Perspectives of Physical Activity Programs for Older Adults With Cognitive Impairment.

Objectives: Physical activity (PA) is beneficial for older adults' cognition. There is limited research investigating perspectives of support persons (SPs) of next-of-kins (NOKs) with cognitive impairment. This exploratory study aimed to investigate perspectives of SPs of older adults with Alzheimer's Dementia (AD) or Mild Cognitive Impairment (MCI). Methods: A telephone survey of 213 SPs of NOKs from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing (AIBL) was undertaken to quantitatively assess SPs' beliefs and knowledge about PA benefits, current PA level of their NOK, and PA program preferences. The contribution of age, gender, diagnosis and mental health symptoms was assessed using multiple logistic regression analyses. Results: Many SPs were aware of PA benefits for memory (64%) and believed it would help their NOK (72%). Older SP age was associated with less awareness of benefits (p = 0.016). SPs caring for male NOKs were more likely to believe that PA would be helpful than those caring for female NOKs (p = 0.049). NOK AD diagnosis (rather than MCI) (p = 0.014), older age (p = 0.005) and female gender (p = 0.043) were associated with lower PA levels. SPs were mixed regarding preference for their NOKs to participate in individual (45%) or group (54%) PA. Many SPs wanted to participate in PA with their NOK (63%). Conclusions: The results highlight that SPs have high levels of awareness of the cognitive benefits of PA, and describe their preferences regarding PA programs. The findings provide new information to inform targeted public health messaging, PA prescribers and providers, and future research directions.

A Randomized Controlled Trial on the Effects of a 6-Month Home-Based Physical Activity Program with Individual Goal-Setting and Volunteer Mentors on Physical Activity, Adherence, and Physical Fitness in Inactive Older Adults at Risk of Cognitive Decline: The INDIGO Study.

BACKGROUND: Increasing physical activity (PA) in those who have memory concerns requires innovative approaches. OBJECTIVE: To compare in this randomized controlled trial (RCT) the effects on PA, adherence, and fitness of two approaches to deliver a 6-month home-based PA program in older, inactive individuals at risk of cognitive decline. METHODS: Individuals (n = 52) aged 60-85 years, inactive with mild cognitive impairment or subjective cognitive decline were recruited from the community and memory clinics. Randomization was to 6 months of 150 min/week moderate intensity PA with either: goal-setting with mentor support; or education and peer contact. A subset of participants (n = 36) continued for a further 6 months. PA, moderate and vigorous PA, and secondary outcomes, fitness, goal performance/satisfaction and self-efficacy were assessed at baseline, 6 and 12 months. Modelling of primary and secondary outcomes was conducted with linear mixed models. RESULTS: Participants were mean age (±sd) 70.1 (6.4) years. Six-month retention was 88.5%(n = 46). No significant between-group differences were observed for PA or fitness. Post-hoc combined group data showed a significant, moderate-large effect size increase in PA with time. PA increased by a mean 1,662 (943, 2383) steps/day (95%CI) and 1,320 (603, 2037) steps/day at 6 and 12 months (p < 0.001). Median (quartiles Q1-Q3) 6 and 6-12 month combined group adherence was 88.9 (74.4-95.7)%and 84.6 (73.9-95.4)%respectively. CONCLUSION: In this target group, no differences were detected between groups both intervention strategies were highly effective in increasing PA and fitness.

Ethnic Differences in Barriers and Enablers to Physical Activity Among Older Adults.

Despite its well-known health benefits, most older adults do not commit to undertaking sufficient physical activity (PA). In this study we aimed to examine the perceived benefits of and barriers and enablers to PA from the perspectives of older Caucasian and Chinese adults living in Australia. Individual and group interviews with 17 Caucasian (mean age: 72.8 years) and 47 Chinese adults (mean age: 74.0 years) were conducted and analysed using thematic analysis. Overall, participants knew about the benefits of PA on physical health but had inconsistent views on its benefits on mental and cognitive health. Older Caucasian and Chinese adults reported similar barriers (e.g., health issues, costs, bad weather and lack of time) and enablers (e.g., improving health; environmental enablers such as adequate and walkable spaces and good natural environment; peer support; and self-motivation) to PA. In comparison, older Chinese adults reported barriers more often, and reported some unique barriers relating to language and culture issues. The findings contribute to developing targeted PA programs for older Caucasian and Chinese adults.

Fifteen Years of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study: Progress and Observations from 2,359 Older Adults Spanning the Spectrum from Cognitive Normality to Alzheimer's Disease.

BACKGROUND: The Australian Imaging, Biomarkers and Lifestyle (AIBL) Study commenced in 2006 as a prospective study of 1,112 individuals (768 cognitively normal (CN), 133 with mild cognitive impairment (MCI), and 211 with Alzheimer's disease dementia (AD)) as an 'Inception cohort' who underwent detailed ssessments every 18 months. Over the past decade, an additional 1247 subjects have been added as an 'Enrichment cohort' (as of 10 April 2019). OBJECTIVE: Here we provide an overview of these Inception and Enrichment cohorts of more than 8,500 person-years of investigation. METHODS: Participants underwent reassessment every 18 months including comprehensive cognitive testing, neuroimaging (magnetic resonance imaging, MRI; positron emission tomography, PET), biofluid biomarkers and lifestyle evaluations. RESULTS: AIBL has made major contributions to the understanding of the natural history of AD, with cognitive and biological definitions of its three major stages: preclinical, prodromal and clinical. Early deployment of Aß-amyloid and tau molecular PET imaging and the development of more sensitive and specific blood tests have facilitated the assessment of genetic and environmental factors which affect age at onset and rates of progression. CONCLUSION: This fifteen-year study provides a large database of highly characterized individuals with longitudinal cognitive, imaging and lifestyle data and biofluid collections, to aid in the development of interventions to delay onset, prevent or treat AD. Harmonization with similar large longitudinal cohort studies is underway to further these aims.

Online Personalised Training in Memory Strategies for Everyday (OPTIMiSE) Program for Older Adults with Cognitive Concerns: Pilot Study Protocol.

Memory interventions for older adults with cognitive concerns result in improved memory performance and maintenance of cognitive health. These programs are typically delivered face-to-face, which is resource intensive and creates access barriers, particularly for those with reduced mobility, limited transportation, and living in rural or remote areas. The COVID-19 pandemic has created an additional access barrier, given the increased risk this disease poses to older adults. Internet-based interventions seek to overcome these barriers. This paper describes the protocol of a pilot study that aims to evaluate the feasibility, acceptability, and efficacy of one such internet-based intervention: the Online Personalised Training in Memory Strategies for Everyday (OPTIMiSE) program. OPTIMiSE focuses on improving knowledge regarding memory and providing training in effective memory strategies for everyday life. The pilot study described in this protocol will be a single-arm pre-post study of 8 weeks duration, with a single maintenance session 3 months post-intervention. Participants will be Australian adults aged ≥60 years reporting cognitive changes compared with 10 years ago. Primary outcome measures will address feasibility, acceptability, and efficacy. Secondary outcome measures assessing sense of community and self-efficacy will be administered at the 8-week and 3-month timepoints. Data collection will conclude mid-2021, and results will be presented in a subsequent publication. Translation of memory interventions to internet-based delivery has the potential to remove many access barriers for older adults; however, the acceptability and feasibility of this modality needs investigation. OPTIMiSE is the initial step in what could be an important program enabling access to an evidence-based memory intervention for older adults worldwide. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12620000979954.

Dementia knowledge and associated factors among older Chinese adults: a cross-national comparison between Melbourne and Beijing.

OBJECTIVES: This study compared dementia knowledge between older Chinese adults in Melbourne, Australia, and Beijing, China, and explored factors associated with dementia knowledge between these two groups. Ultimately, this study aimed to inform the development of tailored dementia education programs for older Chinese adults. DESIGN: A cross-sectional design was employed in this study. SETTING: Participants were recruited from 5 Chinese community senior groups in Melbourne and 10 community health centers in Beijing from March to May 2019. PARTICIPANTS: A total of 379 older Chinese adults aged 50 and over completed the questionnaire, including 153 from Melbourne and 226 from Beijing. MEASUREMENTS: Dementia knowledge was assessed using the Alzheimer's Disease Knowledge Scale (ADKS). Demographic characteristics, dementia-related experience, and the mental health status of participants were collected. Stepwise linear regression was used to analyze the factors associated with dementia knowledge. RESULTS: In general, older Chinese adults in Melbourne and Beijing reported similar levels of dementia knowledge for both the overall ADKS scale (mean ± SD: 17.2 ± 2.9 in Melbourne vs. 17.5 ± 2.9 in Beijing, p > 0.05) and the seven subdomains. Of the subdomains, the highest correct response rates were observed in the life impact of the dementia subdomain, and the lowest rates were observed in the caregiving subdomain. Stepwise linear regression analysis revealed that younger age and self-reported dementia worry were significantly associated with higher levels of dementia knowledge in the Melbourne group, whereas a positive family history of dementia was significantly associated with higher levels of dementia knowledge in the Beijing group. CONCLUSIONS: Older Chinese adults living in Melbourne and Beijing share similar levels of dementia knowledge, but factors associated with their knowledge are different. These findings will inform the development of culturally and socially appropriate dementia education programs for older Chinese populations in different countries.

Assessment of the DTI-ALPS Parameter Along the Perivascular Space in Older Adults at Risk of Dementia.

BACKGROUND AND PURPOSE: Recently, there has been growing interest in the glymphatic system (the functional waste clearance pathway for the central nervous system and its role in flushing solutes (such as amyloid ß and tau), metabolic, and other cellular waste products in the brain. Herein, we investigate a recent potential biomarker for glymphatic activity (the diffusion tensor imaging along the perivascular space [DTI-ALPS] parameter) using diffusion MRI imaging in an elderly cohort comprising 10 cognitively normal, 10 mild cognitive impairment (MCI), and 16 Alzheimer's disease (AD). METHODS: All 36 participants imaged on a Siemens 3.0T Tim Trio. Single-SE diffusion weighted Echo-planar imaging scans were acquired as well as T1 magnetization prepared rapid gradient echo, T2 axial, and susceptibility weighted imaging. Three millimeter regions of interest were drawn in the projection and association fibers adjacent to the medullary veins at the level of the lateral ventricle. The DTI-ALPS parameter was calculated in these regions and correlated with cognitive status, Mini-Mental State Examination (MMSE), and ADASCog11 measures. RESULTS: Significant correlations were found between DTI-ALPS and MMSE and ADASCog11 in the right hemisphere adjusting for age, sex, and APoE ε4 status. Significant differences were also found in the right DTI-ALPS indices between cognitively normal and AD groups (P < .026) and MCI groups (P < .025) in a univariate general linear model corrected for age, sex, and APoE ε4. Significant differences in apparent diffusion coefficient between cognitively normal and AD groups were found in the right projection fibers (P = .028). CONCLUSION: Further work is needed to determine the utility of DTI-ALPS index in larger elderly cohorts and whether it measures glymphatic activity.

Aggregation of Abnormal Memory Scores and Risk of Incident Alzheimer's Disease Dementia: A Measure of Objective Memory Impairment in Amnestic Mild Cognitive Impairment.

OBJECTIVES: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer's disease (AD) dementia. METHODS: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ -1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. RESULTS: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81-.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40-2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. CONCLUSIONS: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

Combined physical and cognitive training for older adults with and without cognitive impairment: A systematic review and network meta-analysis of randomized controlled trials.

Combining physical exercise with cognitive training is a popular intervention in dementia prevention trials and guidelines. However, it remains unclear what combination strategies are most beneficial for cognitive and physical outcomes. We aimed to compare the efficacy of the three main types of combination strategies (simultaneous, sequential or exergaming) to either intervention alone or control in older adults. Randomized controlled trials of combined cognitive and physical training were included in multivariate and network meta-analyses. In cognitively healthy older adults and mild cognitive impairment, the effect of any combined intervention relative to control was small and statistically significant for overall cognitive (k = 41, Hedges' g = 0.22, 95 % CI 0.14 to 0.30) and physical function (k = 32, g = 0.25, 95 % CI 0.13 to 0.37). Simultaneous training was the most efficacious approach for cognition, followed by sequential combinations and cognitive training alone, and significantly better than physical exercise. For physical outcomes, simultaneous and sequential training showed comparable efficacy as exercise alone and significantly exceeded all other control conditions. Exergaming ranked low for both outcomes. Our findings suggest that simultaneously and sequentially combined interventions are efficacious for promoting cognitive alongside physical health in older adults, and therefore should be preferred over implementation of single-domain training.

Combined effects of continuous exercise and intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides in adults with obesity: a randomized crossover trial.

BACKGROUND: Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides. METHODS: Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m- 2 SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points. RESULTS: When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1-4.1%] and EX+BR by 3% [0.6-4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11-22%] and 21% [8-33%], respectively; and EX+BR reduced values by 25% [19-31%] and 28% [15-38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1-10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1-8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides. CONCLUSIONS: Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ( ACTRN12614000737639 ).

Impact of APOE-ε4 carriage on the onset and rates of neocortical Aß-amyloid deposition.

Neocortical Aß-amyloid deposition, one of the hallmark pathologic features of Alzheimer's disease (AD), begins decades prior to the presence of clinical symptoms. As clinical trials move to secondary and even primary prevention, understanding the rates of neocortical Aß-amyloid deposition and the age at which Aß-amyloid deposition becomes abnormal is crucial for optimizing the timing of these trials. As APOE-ε4 carriage is thought to modulate the age of clinical onset, it is also important to understand the impact of APOE-ε4 carriage on the age at which the neocortical Aß-amyloid deposition becomes abnormal. Here, we show that, for 455 participants with over 3 years of follow-up, abnormal levels of neocortical Aß-amyloid were reached on average at age 72 (66.5-77.1). The APOE-ε4 carriers reached abnormal levels earlier at age 63 (59.6-70.3); however, noncarriers reached the threshold later at age 78 (76.1-84.4). No differences in the rates of deposition were observed between APOE-ε4 carriers and noncarriers after abnormal Aß-amyloid levels had been reached. These results suggest that primary and secondary prevention trials, looking to recruit at the earliest stages of disease, should target APOE-ε4 carriers between the ages of 60 and 66 and noncarriers between the ages of 76 and 84.

Baseline White Matter Is Associated With Physical Fitness Change in Preclinical Alzheimer's Disease.

White matter (WM) microstructure is a sensitive marker to distinguish individuals at risk of Alzheimer's disease. The association of objective physical fitness (PF) measures and WM microstructure has not been explored and mixed results reported with physical activity (PA). Longitudinal studies of WM with PA and PF measures have had limited investigation. This study explored the relationship between objective PF measures over 24-months with "normal-appearing" WM microstructure. Data acquired on magnetic resonance imaging was used to measure "normal-appearing" WM microstructure at baseline and 24-months. Clinical variables such as cognitive and blood-based measures were collected longitudinally. Also, as part of the randomized controlled trial of a PA, extensive measures of PA and fitness were obtained over the 24 months. Bilateral corticospinal tracts (CST) and the corpus callosum showed a significant association between PF performance over 24-months and baseline WM microstructural measures. There was no significant longitudinal effect of the intervention or PF performance over 24-months. Baseline WM microstructural measures were significantly associated with PF performance over 24-months in this cohort of participants with vascular risk factors and at risk of Alzheimer's disease with distinctive patterns for each PF test.