The association between apathy and frailty in older adults: a new investigation using data from the Mapt study.

INTRODUCTION: Apathy is a behavioral syndrome that has been suggested to share similar neuro-physiological pathways with frailty. OBJECTIVE: To investigate the cross-sectional association between apathy and frailty using original data from dementia-free, community-dwelling older adults. METHOD: A cross-sectional analysis was performed to test the association between frailty (according to Fried's frailty phenotype) and apathy (defined by three items from Geriatric Depression Scale) using data from MAPT, a 3-year, randomized, multicenter, placebo-controlled trial among community-dwelling, dementia-free participants (1.679 individuals with mean age of 75 years). RESULTS: The ordinal logistic regression showed that apathetic individuals had a two-fold more probability to be rated as frail (OR 2.20, 95% CI 1.7-2.9), when adjusting for confounders. Apathetic individuals display a two-fold more likelihood to be rated as pre-frail (RRR 2.1; 95% CI 1.5-2.8) and a three-fold higher probability to be rated as frail (RRR 3.5, 95% CI 1.8-6.9) compared to robust participants. CONCLUSION: Although data on the associations between apathy and frailty are scarce, these conditions potentially shares physiological mechanisms and were found to be closely associated. Temporal association between frailty and apathy deserve to be further investigated.

Six-month observational follow-up on activities of daily living in people with dementia living in nursing homes after a 6-month group based on either exercise or social activities.

BACKGROUND: Studies have demonstrated changes in activities of daily living after an exercise intervention in people with dementia (PWD) living in nursing homes (NH). However, some discrepancies are shown during follow-up. AIMS: Our objective was to measure activities of daily living (ADL) performance during a 6-month observational follow-up after a 6-month exercise or social activity intervention in PWD living in NH. METHODS: After cluster randomisation, 91 PWD living in NH performed a 6-month structured exercise intervention (n = 44) or a social activity intervention (n = 47). After the intervention, 85 PWD were assessed for post-intervention follow-up. Instrumental and basic activities of daily living (IADL, ADL) were measured at 6-month observational follow-up after the intervention using the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory for Severe Alzheimer's Disease (ADCS-ADL-sev) scale (scores ranging from 0 to 51, higher is better). RESULTS: Compared to participants in the social activity, those who participated to the exercise intervention had a significant decrease of their ADCS-ADL-sev score (between-group adjusted mean difference: 4.6 points, p = 0.001) with IADL having the most decrease (2.8 points, p = 0.004). DISCUSSION: Unexpectedly, exercisers declined sharply in the performance of ADLs and IADLs, whereas participants in the social intervention group maintained their levels. The potential mechanisms to explain these findings remain still to be elucidated.

The impact of post-resistance exercise protein consumption on subsequent appetite and daily energy intake of sarcopenic older men: a pilot study.

BACKGROUND: Because of its satiating effect, it has been widely purported that a high-protein beverage may reduce subsequent appetite and food intake in healthy aged individuals, therefore annihilating any supplemental effect. AIMS: The goal of the study was to examine the impact of a post-exercise protein supplement from dairy products in the hours following resistance exercise on subsequent energy intake, sensation of hunger, appetite and satiety in sarcopenic older men. METHODS: A randomized double-blind crossover study with three experimental conditions was performed. Nine sarcopenic older (64 ± 3 years) men participated in three experimental conditions: post-exercise protein supplementation made from (1) cow's milk (13 g of proteins); (2) rice milk (isocaloric protein-free beverage) and (3) water (control). Subsequent energy intake was measured with a test buffet and a food record over the rest of the day. Assessment of appetite, satiety and hunger were obtained by visual analogue scales at various times before and after the buffet. RESULTS: Appetite, feeling of hunger and satiety and subsequent energy intake were not significantly different between the three experimental conditions. However, when participants were supplemented with cow's milk, total fat intake during the day of the intervention was significantly lower than with other supplements (p ≤ 0.05). CONCLUSION: Post-exercise consumption of protein supplements made from dairy products appear not to compromise daily nutritional behavior and does not confer the anticipated negative impact on nutritional intake in sarcopenic older men.

Impact of Mild Hypohydration on Muscle Endurance, Power, and Strength in Healthy, Active Older Men.

Goulet, EDB, Mélançon, MO, Lafrenière, D, Paquin, J, Maltais, M, and Morais, JA. Impact of mild hypohydration on muscle endurance, power, and strength in healthy, active older men. J Strength Cond Res 32(12): 3414-3424, 2018-Under particular circumstances older persons may be vulnerable to developing mild chronic hypohydration. In young adults, hypohydration has been shown to impair muscle endurance, power and strength. Muscle performance declines with aging, a condition known as dynapenia. How hypohydration impacts muscle performance in older persons remains unclear. In this study, we examined this question, believing it may identify a factor exacerbating dynapenia. One-hour after having been passively exposed to heat where either a body mass loss of 1% was induced or euhydration maintained with fluid ingestion, 8 healthy, active older men (age: 68 ± 5 years) completed an exercise testing session where indices of muscle strength (30-second chair stand, grip strength, maximal isometric seated leg-press extension), endurance (seated leg-curl flexion + seated leg-press extension to exhaustion at 60% of 1 repetition maximum), and power (30-second Wingate test) were assessed. Gastrointestinal temperature before exercise testing was not significantly different from that measured before heat exposure with neither hydration regimen. Magnitude-based inferential statistics indicate that from a clinical perspective, the effect of hypohydration on 30-second chair stand (-1.0 ± 4.4%) is possibly harmful, for grip strength (-2.4 ± 4.1%), lower limbs endurance (-7.5 ± 11.2%), and anaerobic power (-3.9 ± 4.3%) likely detrimental, and unclear with respect to maximal isometric lower limb strength. Maintaining adequate hydration in older men is important, since hypohydration of only 1% body mass could impede muscle endurance, power and strength and, consequently, worsen the impact of dynapenia.

Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study.

The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 ± 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM.

Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study.

The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 ± 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM.

The Effect of Resistance Training and Different Sources of Postexercise Protein Supplementation on Muscle Mass and Physical Capacity in Sarcopenic Elderly Men.

The loss of muscle mass (sarcopenia) with aging is related to a progressive loss of muscle strength and physical capacity. Resistance exercise and milk-based protein supplementation have been demonstrated as significant countermeasures for sarcopenia and the loss of muscle strength. However, using high doses of proteins can act as a meal replacement in the elderly. Therefore, we sought to determine whether a standard supplementation (12 g per serving) of protein and resistance training could be an efficient strategy to promote muscle strength and physical capacity in sarcopenic men. Twenty-six participants were randomized in 3 groups in a double-blind control study. All the groups performed exercise and consumed a protein-rich supplement 12 g of protein, 7 g of essential amino acids from milk (n = 8), soy (n = 8), or rice milk (nonprotein control, n = 10). Body composition was measured using dual-energy x-ray absorptiometry. Strength was measured by 1 repetition maximum with different exercises. Different physical capacity measurements were assessed (timed up and go test, chair stand, and walking speed). The results indicated a significant increase in fat-free mass in all groups and changes in muscle strength, with no differences between groups. This study indicates that resistance training is an effective way to increase muscle mass and strength, regardless of protein supplementation. Higher doses of protein-rich foods may have to be recommended to promote muscle mass gains when executing resistance exercise in elderly sarcopenic individuals.

Exercise for Preventing Falls in People with Dementia: Time to Work Together.

Since the last two decades, many systematic reviews and meta-analyses found contradicting results on the effect of exercise in reducing falls in people with dementia. The recently published systematic review in the Journal of Alzheimer's Disease found positive results in reducing falls in only two studies. The authors conclude that insufficient data remains in reducing the number of falls by exercise interventions. This commentary focuses on interdisciplinary approaches that could reduce the number of falls in this vulnerable population.

Cross-sectional and prospective associations between homocysteine and a frailty index: A post-hoc analysis of the multidomain Alzheimer's prevention trial (MAPT).

BACKGROUND: Homocysteine (Hcy) has been associated with several health problems, including reduced physical capacity. No study appears to have looked at the role of Hcy values longitudinally on physical capacity deterioration in older adults. The objective is to examine cross-sectional and prospective associations between Hcy values and frailty in the elderly and investigate Hcy potential association with the onset of frailty. METHODS: 769 community-dwelling older adults from the MAPT study were recruited for this study. Total Hcy was measured at baseline. Frailty was evaluated at 5 different collection timepoints: baseline, 6-month, 1-, 2-, and 3-year using a frailty index (FI) composed of 19 items. Linear regressions adjusted for all the confounders (age, gender, educational level, MAPT group allocation and Omega-3) were performed to examine the cross-sectional associations of homocysteine values with the FI. A cox model was used to test the association of Hcy with the onset of frailty. RESULTS: Mean Hcy values (15.9 ± 5.6 µmol\L) were obtained from 769 community-dwelling adults (75.7 ± 4.6 years old). After adjustments, a significant (ß = 0.002, (00002-0.003)) and positive association between baseline Hcy values and FI was found (ß = 0.002). Additionally, higher values of Hcy were associated with a worsening of FI after 3 years (ß = 0.002, p = 0.003). A significant association between baseline Hcy values and the likelihood of developing frailty was discovered by incident event analysis (HR: 1.04 (1.01-1.06), p = 0.004). CONCLUSION: High levels of Hcy are associated with the fragility process in community-dwelling older adults.

Socio-Demographic Factors Associated With COVID-19 Vaccine Hesitancy Among Middle-Aged Adults During the Quebec's Vaccination Campaign.

Introduction: The objective of this study was to characterize the combinations of demographic and socioeconomic characteristics associated to the unwillingness to receive the COVID-19 vaccines during the 2021 Quebec's vaccination campaign. Materials and Methods: In March-June 2021, we conducted an online survey of the participants of the CARTaGENE population-based cohort, composed of middle-aged and older adults. After comparing the vaccinated and unvaccinated participants, we investigated vaccine hesitancy among participants who were unvaccinated. For identifying homogeneous groups of individuals with respect to vaccine hesitancy, we used a machine learning approach based on a hybrid tree-based model. Results: Among the 6,105 participants of the vaccine cohort, 3,553 (58.2%) had at least one dose of COVID-19 vaccine. Among the 2,552 participants, 221 (8.7%) did not want to be vaccinated (91) or were uncertain (130). The median age for the unvaccinated participants was 59.3 years [IQR 54.7-63.9]. The optimal hybrid tree-based model identified seven groups. Individuals having a household income lower than $100,000 and being born outside of Canada had the highest rate of vaccine hesitancy (28% [95% CI 19.8-36.3]). For those born in Canada, the vaccine hesitancy rate among the individuals who have a household income below $50,000 before the pandemic or are Non-retired was of 12.1% [95% CI 8.7-15.5] and 10.6% [95% CI 7.6-13.7], respectively. For the participants with a high household income before the pandemic (more than $100,000) and a low level of education, those who experienced a loss of income during the pandemic had a high level of hesitancy (19.2% [8.5-29.9]) whereas others who did not experience a loss of income had a lower level of hesitancy (6.0% [2.8-9.2]). For the other groups, the level of hesitancy was low of around 3% (3.2% [95% CI 1.9-4.4] and 3.4% [95% CI 1.5-5.2]). Discussion: Public health initiatives to tackle vaccine hesitancy should take into account these socio-economic determinants and deliver personalized messages toward people having socio-economic difficulties and/or being part of socio-cultural minorities.

Long-chain Omega-3 fatty acids supplementation and cognitive performance throughout adulthood: A 6-month randomized controlled trial.

OBJECTIVE: To investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) supplementation improve cognitive performance and if apolipoprotein E (APOE) genotype or age were effect modifiers. METHODS: Healthy adults of 20 to 80 years old (n = 193) were completed a 6-month double-blind randomized controlled trial with two groups: 2.5 g/day of n-3 PUFA or a placebo. Primary outcomes were visuospatial ability and working memory and secondary outcomes were episodic memory and executive function, measured at baseline and 6 months. RESULTS: Cognitive performances did not significantly differ between groups on primary or secondary outcomes after 6 months of treatment. APOE carriers and age were not effect modifiers for any outcomes. Those with low episodic memory scores and taking the n-3 PUFA supplement, significantly improved their scores (p = 0.043). CONCLUSIONS: A 6-month n-3 PUFA supplementation did not improve cognitive performance in cognitively healthy adults and APOE status or age were not effect modifiers.

Bidirectional relationship between depressive symptoms and physical performance in community-dwelling older people with subjective memory complaints.

PURPOSE: This study examined the bidirectional relationship between depressive symptoms and physical performance in community-dwelling older people with subjective memory complaints. METHODS: Secondary analyses using data from the Multidomain Alzheimer Preventive Trial (MAPT) study were performed. The participants were 1679 subjects (female, 64.8%; mean age, 75.3 ± 4.4 years). The outcome measures were depressive symptoms assessed by the 15-item Geriatric Depression Scale (GDS) and physical performance assessed by the Short Physical Performance Battery (SPPB) and handgrip strength (HGS). All measurements were performed at baseline and at 6, 12, 24, and 36 months. The bidirectional relationships of GDS with SPPB and HGS were examined using mixed-effect regression analysis. RESULTS: Baseline physical performance was significantly associated with a decreased GDS score (SPPB score: ß = - 0.210, 95% confidence interval [CI], - 0.283 to - 0.137; HGS: ß = - 0.038, 95% CI - 0.056 to - 0.019). The baseline GDS score was significantly associated with decreased physical performance (SPPB score: ß = - 0.082, 95% CI - 0.107 to - 0.056; HGS: ß = - 0.261, 95% CI - 0.370 to - 0.152). CONCLUSION: Since depressive symptoms and physical performance had a bidirectional relationship, prevention or improvement of decreased physical performance could play a role in reducing depressive symptoms, and addressing depressive symptoms may play a role in improving physical performance. TRIAL REGISTRATION NUMBER: NCT01513252.

Exercise Effects on Falls, Fractures, Hospitalizations, and Mortality in Older Adults With Dementia: An Individual-Level Patient Data Meta-analysis.

BACKGROUND: To study the effects of exercise on falls, fractures, hospitalizations, and death in people with dementia. METHOD: We conducted an individual-level patient data meta-analysis of 7 randomized controlled trials (RCTs). We looked for studies from the reference list of previous systematic reviews and undertook an electronic search for articles published between 2013 and 2019 in Ageline, CENTRAL, PsycINFO, PubMed, and SportsDiscus. Main (binary) outcome measures were the risk of mortality, hospitalization, faller, multiple faller, injurious faller, and fractures. Secondary (count) outcomes were the incident rates of hospitalizations, falls, and injurious falls. RESULTS: From the 1314 participants, 771 were allocated to the exercise group and 543 to the control group. The number of cases regarding the main outcome measures in exercisers and controls were, respectively: 45 (5.8%) and 31 (5.7%) deaths; 102 (14.4%) and 65 (13.4%) participants hospitalized; 221 (34.4%) and 175 (41.3%) had at least 1 fall; 128 (20.2%) and 92 (21.7%) had multiple falls; 78 (24.8%) and 92 (29.3%) had injurious falls; and 19 (2.9%) and 15 (3.5%) had suffered a fracture. Two-step meta-analysis found no effects of exercise on any outcome. One-step meta-analysis found exercise reduced the risk of falls (odds ratio 0.75; 95% CI: 0.57-0.99). Exploratory analysis showed exercise decreased the rate of incident falls in participants with the lowest functional ability (incident rate ratio 0.48; 95% CI: 0.30-0.79). CONCLUSIONS: Although the 2-step meta-analysis suggests exercise does not have an effect on the outcomes, 1-step meta-analysis suggested that exercise may reduce fall risk. Data from further high-quality RCTs are still needed.

Metabolism of Exogenous D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart and Kidney.

There is growing interest in the metabolism of ketones owing to their reported benefits in neurological and more recently in cardiovascular and renal diseases. As an alternative to a very high fat ketogenic diet, ketones precursors for oral intake are being developed to achieve ketosis without the need for dietary carbohydrate restriction. Here we report that an oral D-beta-hydroxybutyrate (D-BHB) supplement is rapidly absorbed and metabolized in humans and increases blood ketones to millimolar levels. At the same dose, D-BHB is significantly more ketogenic and provides fewer calories than a racemic mixture of BHB or medium chain triglyceride. In a whole body ketone positron emission tomography pilot study, we observed that after D-BHB consumption, the ketone tracer 11C-acetoacetate is rapidly metabolized, mostly by the heart and the kidneys. Beyond brain energy rescue, this opens additional opportunities for therapeutic exploration of D-BHB supplements as a "super fuel" in cardiac and chronic kidney diseases.

Prospective Associations Between Diffusion Tensor Imaging Parameters and Frailty in Older Adults.

BACKGROUND: Cross-sectional associations have been found between frail individuals and worse white matter (WM) integrity. However, the prospective association between WM integrity and frailty is still unclear. Our objectives were to measure associations between WM integrity using diffusion tensor imaging (DTI) and the 5-year worsening of frailty in community-dwelling older adults. DESIGN: Secondary analysis of the randomized controlled Multidomain Alzheimer Preventive Trial (MAPT). SETTING: Thirteen memory centers in France and Monaco between 2008 and 2011. PARTICIPANTS: Participants (mean age = 74.7 ± 3.9 years) with no dementia at baseline who had functional magnetic resonance imaging performed as part of the MAPT study (n = 227). MEASUREMENTS: Fractional anisotropy and mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) were acquired for 10 different brain regions. Frailty was assessed by the Fried frailty phenotype (score from 0 to 5, higher is worse) at up to seven time points for 5 years. Mixed effect ordinal logistic regression model was used to assess the prospective association between DTI parameters (independent variables) and frailty (dependent variable). All the analyses were adjusted for age, sex, baseline total intracranial volume, and the presence of one of the following cardiovascular risk factors (hypertension, diabetes, and/or hypercholesterolemia). RESULTS: A statistically significant association was found between the RD, AxD, and MD for different brain regions (anterior limb of internal capsule, external capsule, posterior corona radiata, posterior thalamic radiation, superior corona radiata, superior frontal occipital fasciculus, and superior longitudinal fasciculus) and worsening of frailty over 5 years after adjusting for multiple comparisons. CONCLUSIONS: This is the first study to show that WM integrity is associated with frailty in older adults. The mechanisms related to these results require further investigation. J Am Geriatr Soc 68:1050-1055, 2020.

Prospective associations between physical activity levels and white matter integrity in older adults: results from the MAPT study.

BACKGROUND: Higher levels of physical activity (PA) are known to be associated with better white matter integrity measured by diffusion tensor imaging (DTI) in older adults in cross-sectional studies. However, no studies have investigated the association between PA levels and the evolution of DTI parameters (fractional anisotropy and mean diffusivity). OBJECTIVES: To examine the cross-sectional associations between PA levels and DTI parameters, then to investigate the association between baseline PA levels and the evolution of DTI parameters in older adults. METHODS: Data on magnetic resonance imaging with DTI method from the Multidomain Alzheimer's Preventive Trial (MAPT) study were used; 228 participants had data on DTI measured at three time-points over five years. Fractional anisotropy and mean diffusivity were acquired for six different brain regions. RESULTS: No significant associations were found in the cross-sectional analyses. Only one association was found: compared with active individuals, a faster worsening in the mean diffusivity of the uncinate fasciculus region was found in inactive individuals (-5.0 × 10-6 (-9.5 × 10-5, 4.9 × 10-6)). CONCLUSIONS: In this study, we found that the condition of the uncinate fasciculus region may be susceptible to changes in PA levels in older adults. Longitudinal studies that assess fitness and PA using objective measurements (e.g. cardiorespiratory fitness and accelerometry) could shed some new light on this topic.

Association of Long-term Exercise Training With Risk of Falls, Fractures, Hospitalizations, and Mortality in Older Adults: A Systematic Review and Meta-analysis.

Importance: Long-term exercise benefits on prevalent adverse events in older populations, such as falls, fractures, or hospitalizations, are not yet established or known. Objective: To systematically review and investigate the association of long-term exercise interventions (≥1 year) with the risk of falls, injurious falls, multiple falls, fractures, hospitalization, and mortality in older adults. Data Sources: PubMed, Cochrane Central Register of Controlled Trials, SportDiscus, PsychInfo, and Ageline were searched through March 2018. Study Selection: Exercise randomized clinical trials (RCTs) with intervention length of 1 year or longer, performed among participants 60 years or older. Data Extraction and Synthesis: Two raters independently screened articles, abstracted the data, and assessed the risk of bias. Data were combined with risk ratios (RRs) using DerSimonian and Laird's random-effects model (Mantel-Haenszel method). Main Outcomes and Measures: Six binary outcomes for the risk of falls, injurious falls, multiple falls (≥2 falls), fractures, hospitalization, and mortality. Results: Forty-six studies (22 709 participants) were included in the review and 40 (21 868 participants) in the meta-analyses (mean [SD] age, 73.1 [7.1] years; 15 054 [66.3%] of participants were women). The most used exercise was a multicomponent training (eg, aerobic plus strength plus balance); mean frequency was 3 times per week, about 50 minutes per session, at a moderate intensity. Comparator groups were often active controls. Exercise significantly decreased the risk of falls (n = 20 RCTs; 4420 participants; RR, 0.88; 95% CI, 0.79-0.98) and injurious falls (9 RTCs; 4481 participants; RR, 0.74; 95% CI, 0.62-0.88), and tended to reduce the risk of fractures (19 RTCs; 8410 participants; RR, 0.84; 95% CI, 0.71-1.00; P = .05). Exercise did not significantly diminish the risk of multiple falls (13 RTCs; 3060 participants), hospitalization (12 RTCs; 5639 participants), and mortality (29 RTCs; 11 441 participants). Sensitivity analyses provided similar findings, except the fixed-effect meta-analysis for the risk of fracture, which showed a significant effect favoring exercisers (RR, 0.84; 95% CI, 0.70-1.00; P = .047). Meta-regressions on mortality and falls suggest that 2 to 3 times per week would be the optimal exercise frequency. Conclusions and Relevance: Long-term exercise is associated with a reduction in falls, injurious falls, and probably fractures in older adults, including people with cardiometabolic and neurological diseases.

Longitudinal associations of physical activity levels with morphological and functional changes related with aging: The MAPT study.

INTRODUCTION: The biological process of aging is characterized by molecular and physiological processes that lead to alterations in the organism. There is still a lack of a consensus about the measurement of biological aging, but physical activity (PA) could be a potential marker of an aging phenotype. METHODS: Measurements of body composition, muscle quality (MQ), blood biochemistry, and neurodegeneration were assessed over three years. Physical activity levels were measured using a self-reported questionnaire. RESULTS: Three-year progression of PA levels showed that those who maintained low levels of PA was significantly associated with the evolution of brain and hippocampal volume, compared to inactive individuals. Similar results were found always active individuals, but also had better cognition. CONCLUSION: PA levels are associated with some elements of biological aging, but more studies with objective-based PA measurements could provide a more in-depth knowledge on biological aging.

Prospective association of white matter hyperintensity volume and frailty in older adults.

BACKGROUND: Frailty is a prevalent geriatric condition and its association with brain health is still weakly investigated. The objective of this study was to examine whether brain white matter hyperintensities (WMH) were related to longitudinal changes in frailty severity in community-dwelling older adults. METHODS: 113 community-dwelling older adults, aged 70 years and over, enrolled in the placebo group from the 3-year Multidomain Alzheimer's Preventive Trial (MAPT). Frailty was assessed using Fried's frailty phenotype as an ordinal variable (range from 0 to 5, higher is worse) at baseline, 6, 12, 24 and 36 months. We obtained brain WMH data using magnetic resonance imaging (MRI) at the first and last year of the trial. The progression of WMH volume was evaluated. RESULTS: We included 113 baseline and 83 follow-up MRIs in this study. The median baseline WMH volume was 10.6 (6.0, 15.0) cm3 and the median progression of WMH was 1.1 (-0.3, 2.2) cm3. Our results indicate that people with higher baseline WMH had a 6% increased likelihood of increasing their frailty phenotype score (adjusted OR: 1.06, (1.00-1.12, p = 0.036)). No associations were found between the progression of WMH (slow vs. fast) volume accumulation and frailty severity. CONCLUSION: WMH were associated with frailty severity over time. Why the progression of WMH was not associated with changes in frailty severity requires further investigation.

Association Between Brain ß-Amyloid and Frailty in Older Adults.

BACKGROUND: We sought to determine whether cortical and regional ß-amyloid (Aß) were cross-sectionally and prospectively associated with change in frailty status in older adults. METHODS: We used data from 269 community-dwelling participants from the Multidomain Alzheimer's Preventive Trial (MAPT) who were assessed for brain Aß using positron-emission tomography scan. Regional and cortical-to-cerebellar standardized uptake value ratios were obtained. Frailty was assessed by a frailty index composed of 19 items not directly linked to cognition and Alzheimer's disease. RESULTS: A significant and positive cross-sectional and prospective relationship was found for Aß in the anterior putamen (cross-sectional: ß = 0.11 [0.02-0.20], p = .02; prospective: ß = 0.11 [0.03-0.19], p = .007), posterior putamen (cross-sectional: ß = 0.12 [0.009-0.23], p = .03; prospective: ß = 0.11 [0.02-0.21], p = .02), and precuneus regions (cross-sectional: ß = 0.07 [0.01-0.12], p = .01; prospective: ß = 0.07 [0.01-0.12], p = .01) with increasing frailty. CONCLUSIONS: This study has found new information regarding cross-sectional and prospective positive associations between region-specific brain Aß deposits and worsening frailty. The potential mechanisms involved require further investigation.