Investigating three ways of measuring the intrinsic capacity domain of vitality: nutritional status, handgrip strength and ageing biomarkers.

BACKGROUND: Vitality is conceptually considered as the underlying capacity influencing other intrinsic capacity (IC) domains and being related to nutrition, physiological reserve and biological ageing. However, there is no consensus on its operationalisation. OBJECTIVE: To investigate the structure and magnitude of the association of vitality with other IC domains and functional difficulties using three operational definitions of vitality. METHODS: We included 1,389 older adults from the Multidomain Alzheimer Preventive Trial with data on Mini Nutritional Assessment (MNA), handgrip strength and plasma biomarkers (comprising inflammatory and mitochondrial markers). Using path analysis, we examined the effects of vitality on difficulties in basic and instrumental activities of daily living (ADL and IADL) exerted directly and indirectly through the mediation of other IC domains: cognition, locomotion, psychological, vision and hearing. We further explored the longitudinal association of vitality with IC domains, ADL and IADL over 4 years using linear mixed-effect regression. RESULTS: We observed significant indirect effects of vitality on IADL, mainly through cognitive, locomotor and psychological domains, regardless of the vitality measurement. Participants with higher vitality had fewer IADL difficulties at follow-up (MNA score: ß [95% CI] = -0.020 [-0.037, -0.003]; handgrip strength: -0.011 [-0.023, 0.000]; plasma biomarker-based index: -0.015 [-0.028, -0.002]). Vitality assessed with the plasma biomarker-based index predicted improved locomotion over time. CONCLUSION: Vitality was associated with disability primarily through the mediation of other IC domains. The three indicators examined are acceptable measurements of vitality; biomarkers might be more suitable for the early detection of locomotion decline.

Fatigue in Alzheimer's disease: biological basis and clinical management-a narrative review.

BACKGROUND: Fatigue is a common symptom in neurodegenerative diseases and is associated with decreased cognitive performances. A full knowledge of the causes and physiopathological pathways leading to fatigue in Alzheimer's disease could help treating this symptom and obtain positive effects on cognitive functions. OBJECTIVES: To provide an overview of the clinical conditions and the biological mechanisms leading to fatigue in Alzheimer's disease patients. To review the recent advances on fatigue management and describe the landscape of future possibilities. METHODS: We performed a narrative review including all type of studies (e.g. cross-sectional and longitudinal analysis, reviews, clinical trials). RESULTS: We found very few studies considering the symptom fatigue in Alzheimer's disease patients. Populations, designs, and objectives varied across studies rendering comparability across studies difficult to perform. Results from cross-sectional and longitudinal analysis suggest that the amyloid cascade may be involved in the pathogenesis of fatigue and that fatigue may be a prodromal manifestation of Alzheimer's disease. Fatigue and neurodegeneration of Alzheimer's disease could share common brain signatures (i.e. hippocampal atrophy and periventricular leukoaraiosis). Some mechanisms of aging (i.e. inflammation, mitochondrial dysfunction, telomere shortening) may be proposed to play a common underlying role in Alzheimer's disease neurodegeneration and muscle fatigability. Considering treatments, donepezil has been found to reduce cognitive fatigue in a 6-week randomized controlled study. Fatigue is frequently reported as an adverse event in patients treated by anti-amyloid agents in clinical trials. CONCLUSION: The literature is actually inconclusive about the main causes of fatigue in Alzheimer's disease individuals and its potential treatments. Further research is needed to disentangle the role of several components such as comorbidities, depressive symptoms, iatrogenic factors, physical decline and neurodegeneration itself. Given the clinical relevance of this symptom, it seems to be important to systematically assess fatigue by validated tools in Alzheimer's disease clinical trials.

Cross-sectional associations of dietary intake with hearing and vision capacities and potential mediation effect of inflammation in older adults: the COGFRAIL study.

BACKGROUND: Considering their prevalence and burden, information on the sensory impairment etiology is essential. Links between nutrition and sensory impairment through inflammation have been suggested. Although the decline in sensory capacities is age-related, few research included a geriatric population. AIMS: Exploring the associations of nutrition with sensory capacities and test inflammation as a mediator among cognitively and physically impaired older adults. METHODS: Cross-sectional data from the COGFRAIL cohort, including 164 participants with no hearing aid and 20 participants wearing no visual aid. Hearing was evaluated using the Hearing Handicap Inventory for the Elderly-screening version (on 40 points, the lower the better), and the Monoyer chart (one to ten out of ten points, the higher the better), and the Parinaud scale (from 1.5, the best, to 28 points, the worst) assessed distant and near vision, respectively. Dietary intake was assessed through a diet history interview and inflammation was measured by the C-Reactive Protein level. Multivariate linear regressions were performed and Structural Equation Modeling (SEM) framework was used to explore the potential mediation effect of inflammation on the diet-hearing relationships. RESULTS: None of the nutrients was significantly associated with hearing acuity in the regressions or the SEM model. Regarding vision, a higher intake of saturated fatty acids was related to lower long-distance visual acuity, and greater Omega-3 consumption was associated with better near-vision capacity. DISCUSSION: No nutrient was associated with hearing capacity and relationships between fatty acids quality and vision acuity were suggested. CONCLUSION: These exploratory results require further investigations.

Effects of a 12-week Vivifrail exercise program on intrinsic capacity among frail cognitively impaired community-dwelling older adults: secondary analysis of a multicentre randomised clinical trial.

INTRODUCTION: The World Health Organisation recently defined the construct of intrinsic capacity (IC), a function-based marker of older adult's health encompassing all mental and physical capacities of the individual. Multicomponent physical exercise (MCE) is a potential intervention capable to maintain/increase IC at older age; however, evidence is scarce on the effects of MCE on IC in cognitively impaired pre-frail/frail older adults. METHODS: Secondary analyses of a randomised clinical trial. One hundred and eighty-eight older outpatients (age = 84.06 ± 4.77, 70.2% women) presenting with pre-frailty/frailty (according to Fried Criteria) and mild cognitive impairment (MCI)/mild dementia were recruited in the Geriatric clinics of three tertiary hospitals in Spain. Subjects were randomised to participate in the 12-week home-based individualised Vivifrail MCE or usual care. An IC index was created based on the z-score of the locomotion (Short Physical Performance Battery), cognitive (Montreal Cognitive Assessment), psychology (15-item Geriatric Depression Scale Yesavage) and vitality (handgrip strength) domains. RESULTS: After the 3-month intervention, linear mixed models showed significant between-group differences in the evolution of the IC composite score (ß=0.48; 95% confidence interval [CI] = 0.24, 0.74; P < 0.001), IC Locomotion (ß = 0.42; 95% CI = 0.10, 0.74; P < 0.001), IC Cognition (ß = 0.45; 95% CI = 0.03, 0.87; P < 0.05) and IC Vitality domains (ß = 0.50; 95% CI = 0.25, 0.74 at 3-month) favouring the MCE group. CONCLUSIONS: The 12-week Vivifrail multicomponent exercise program is an effective strategy to enhance IC, especially in terms of locomotion, cognition and vitality IC domains in community-dwelling older adults with pre-frailty/frailty and MCI/mild dementia, compared to usual care.

Z-drugs and falls in nursing home patients: data from the INCUR study.

BACKGROUND: Z-drugs are the most prescribed treatment for insomnia, but their negative effect on the body sway can increase the risk of falls. AIMS: Evaluating the association between Z-drugs and falls in a resident cohort. METHODS: Prospective observational study using the data collected in the Incidence of pNeumonia and related ConseqUences in nursing home Residents (INCUR) study. RESULTS: During the one-year follow-up, among the 800 participants (median age 87), 93 individuals fell (64 fracturing and 29 without fracturing). Lower calf circumference (adjusted OR 0.92, 95% CI 0.86-0.97, p = 0.006) and the use of selective serotonin reuptake inhibitors (adjusted OR 1.86, 95% CI 1.1-3.05, p = 0.01) predicted falls, whereas the use of Z-drugs (adjusted OR 2.37, 95% CI 1.13-4.94, p = 0.02) and lower body mass index (adjusted OR 0.9, 95% CI 0.84-0.97, p = 0.005) were associated with falls without fractures. CONCLUSIONS: Z-drugs predicted falls without fractures in residents. Alternative strategies to promote sleep in residents should be pursued.

Neuroimaging correlates of persistent fatigue in older adults: A secondary analysis from the Multidomain Alzheimer Preventive Trial (MAPT) trial.

OBJECTIVES: Fatigue has been suggested as a marker of biological aging. It seems plausible that this symptom might be associated with changes in brain health. The objective of this study was to examine the associations between persistent fatigue and neuroimaging correlates in a non-disease-specific population of community-dwelling older adults. METHODS: We performed a cross-sectional analysis using data from The Multidomain Alzheimer Preventive Trial (MAPT). We included 458 subjects. Persistent fatigue was defined as meeting exhaustion criterion of Fried frailty phenotype in two consecutive clinical visits six months apart between study baseline and one year. Brain imaging correlates, assessed by magnetic resonance imaging (MRI), were the outcomes. The associations between persistent fatigue and brain correlates were explored using mixed model linear regressions with random effect at the center level. RESULTS: The mean age of the participants was 74.8 ± 4 years old, and 63% of the subjects were women. Forty-seven participants (10%) exhibited a persistent fatigue profile. People with persistent fatigue were older compared to subjects without persistent fatigue (76.2 years ± 4.3 vs.74.7 ± 3.9 p = 0.009). Persistent fatigue was associated with higher white matter hyperintensity volume in the fully adjusted analysis. We did not find any cross-sectional association between persistent fatigue and sub-cortical volumes and global and regional cortical thickness. CONCLUSION: Persistent fatigue was cross-sectionnally associated with higher white matter hyperintensity volume in older adults. Further longitudinal studies, using an assessment tool specifically designed and validated for measuring fatigue, are needed to confirm our findings.

Malnutrition and physical performance in nursing home residents: results from the INCUR study.

We investigated the association between the risk of malnutrition, assessed through the Mini Nutritional Assessment-Short Form (MNA-SF), and physical performance, measured with the Short Physical Performance Battery (SPPB), in nursing home residents. Moreover, we evaluated which MNA-SF items were most related to the SPPB and the association of the MNA-SF with each SPPB subtest. A total of 499 older people enrolled in the Incidence of pNeumonia and related ConseqUences in nursing home Residents cohort study were examined. Higher scores of MNA-SF were associated with better physical performance (in particular with gait speed). Food intake deficiency, mobility impairment, and recent psychological stress or acute disease were the items of the MNA-SF most associated with the SPPB. In nursing home residents, the MNA-SF and three of its sub-items were significantly correlated with physical performance, independently of potential confounders. In particular, the association was evident for the gait speed subtask of the SPPB.

What day is today? Cognitive capacity and the risk of incident dementia in the context of integrated care for older people (ICOPE Step 1).

Based on clinical observations, our objective was to test if the older adults who failed to recall the name of the weekday, or had a higher number of mistakes in the word recall were at higher risk of mild cognitive impairment (MCI) or dementia. Longitudinal data of the Multidomain Alzheimer Preventive Trial (MAPT) was used to retrospectively measure the cognitive capacity according to the ICOPE Step 1 tool. Incident dementia was assessed by two multidisciplinary committees independent from each other. MCI was defined as Clinical Dementia Rating scale CDR = 0.5. Failure to recall the name of the weekday had a three-fold risk of incident dementia in the next 5 years (HRa = 3.11, 95%CI: 1.18-8.17). Having two or three mistakes in the word recall carried a higher risk of incident dementia, (HRa for two mistakes = 3.50, 95% CI: 1.49-8.26; HRa for three mistakes = 4.28, 95% CI: 1.60-11.46), but not MCI. People with impaired cognitive capacity according to the ICOPE Step 1 tool deserve further assessment and a closer follow-up.

Neuroimaging markers of chronic fatigue in older people: a narrative review.

BACKGROUND: Chronic fatigue is a common symptom in older adults. Although some studies have attempted to identify the neuronal correlates of fatigue associated with chronic diseases, the scientific evidence is scarce regarding fatigue in older people not suffering from a specific disease. AIMS: To gather available evidence of neuroimaging studies investigating the associations between fatigue and brain health in older adults out of the context of a specific disease, and to identify potential brain structures associated with this symptom. METHODS: Studies considering exclusively patients with a specific disease and/or studies focusing on physiological mechanisms of acute fatigue induced by the realization of cognitive and physical tasks were excluded. RESULTS: Very few studies on the associations of fatigue with neuroimaging markers are currently available. Fatigue was associated with reduced hippocampus volumes and with hippocampal amyloid deposition. Regarding the association between fatigue and the circuit of basal ganglia, putamen and thalamus were associated with physical fatigability, whereas amygdala and thalamus with mental fatigability. Very limited evidence about white matter integrity found that healthy individuals with high levels of fatigue had a greater total volume of leukoaraiosis. CONCLUSION: This review suggests that hippocampus damage and potentially loss of function in basal ganglia networks could play a role on chronic fatigue during aging. Further studies are needed to assess the associations of fatigue with white matter alterations.

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.

Reducing potentially inappropriate drug prescribing in nursing home residents: effectiveness of a geriatric intervention.

AIMS: Potentially inappropriate drug prescribing (PIDP) is frequent in nursing home (NH) residents. We aimed to investigate whether a geriatric intervention on quality of care reduced PIDP. METHODS: We performed an ancillary study within a multicentric individually-tailored controlled trial (IQUARE trial). All NH received a baseline and 18-month audit regarding drug prescriptions and other quality of care indicators. After the initial audit, NHs of the intervention group benefited of an in-site intervention (geriatric education for NH staff) provided by a geriatrician from the closest hospital. The analysis included 629 residents of 159 NHs. The main outcome was PIDP, defined as the presence of at least one of the following criteria: (i) drug with an unfavourable benefit-to-risk ratio; (ii) with questionable efficacy; (iii) absolute contraindication; (iv) significant drug-drug interaction. Multivariable multilevel logistic regression models were performed including residents and NH factors as confounders. RESULTS: PIDP was 65.2% (-3.6% from baseline) in the intervention group (n = 339) and 69.9% (-2.3%) in the control group (n = 290). The intervention significantly decreased PIDP [odds ratio (OR) = 0.63; 95% confidence interval 0.40-0.99], as a special care unit in NH (OR = 0.60; (0.42 to 0.85)), and a fall in the last 12 months (OR = 0.63; 0.44-0.90). Charlson Comorbidity Index [ORCCI = 1 vs. 0  = 1.38; 0.87-2.19, ORCCI ≥ 2 vs. 0  = 2.01; (1.31-3.08)] and psychiatric advice and/or hospitalization in a psychiatric unit (OR = 1.53; 1.07-2.18) increased the likelihood of PIDP. CONCLUSION: This intervention based on a global geriatric education resulted in a significant reduction of PIDP at patient level.

Cross-sectional associations of cortical ß-amyloid with erythrocyte membrane long-chain polyunsaturated fatty acids in older adults with subjective memory complaints.

Omega-3 (n-3) and 6 (n-6) polyunsaturated fatty acids (PUFAs) have been associated with reduced cognitive decline in observational studies. Hence, we examined the cross-sectional associations between cortical ß-amyloid (Aß) and erythrocyte membrane PUFAs in 61 non-demented elderly individuals reporting subjective memory complaints from the Multidomain Alzheimer Preventive Trial placebo arm. Cortical-to-cerebellar standard uptake value ratios were obtained using [18 F] florbetapir positron emission tomography. Fatty acids were measured in erythrocyte membranes by gas chromatography. Associations were explored using adjusted multiple linear regression models and were considered significant at p ≤ 0.005 after correction for multiple testing (10 comparisons). We found no significant associations between cortical Aß and erythrocyte membrane PUFAs. The associations closest to significance after adjustment were those between Aß and erythrocyte membrane arachidonic acid (without apolipoprotein E status adjustment: B-coefficient, 0.03; CI, 0.01, 0.05; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, 0.03; CI, 0.00, 0.06; p = 0.04) and Aß and erythrocyte membrane linoleic acid (without apolipoprotein E status adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.02. Including Apolipoprotein E adjustment: B-coefficient, -0.02; CI, -0.04, 0.00; p = 0.09). Furthermore, the association between Aß and erythrocyte membrane arachidonic acid seemed to be specific to Apolipoprotein E ε4 non-carriers (B-coefficient 0.03, CI: 0.00, 0.06, p = 0.03, n = 36). In contrast, no association was found between Aß and erythrocyte membrane linoleic acid in Apolipoprotein E ε4 stratified analysis. Investigating the relationships between Aß and PUFAs longitudinally would provide further evidence as to whether fatty acids, particularly arachidonic acid and linoleic acid, might modulate cognition through Aß-dependent mechanisms.

Effects of a geriatric intervention aiming to improve quality care in nursing homes on benzodiazepine use and discontinuation.

BACKGROUND: Benzodiazepines and "Z drugs" are often prescribed in residents of nursing homes (NH) despite their well-known deleterious effects. We aimed to investigate if a general intervention on quality of care led to discontinuation of benzodiazepine, and to examine which NH-related factors were associated in change of benzodiazepines use. METHODS: IQUARE is a quasi-experimental study, investigating the impact of an intervention based on a geriatric education with NH staff on several quality indicators of care (including appropriate prescriptions). All participating NH received an initial and 18-month audit regarding drug prescriptions and other quality of care variables. The analysis included 3973 residents, 2151 subjects (mean age: 84.6 ± 8.5 years; 74.3% women) in the control group and 1822 (mean age: 85.5 ± 8.1 years; 77.4% women) in the intervention group. Outcomes at 18 months were benzodiazepines use, long-acting benzodiazepines use, new-use of benzodiazepines, and discontinuation. The effect of the intervention was investigated using mixed-effect logistic regression models, including NH variables and residents' health status as confounders. RESULTS: Higher reductions in benzodiazepine use (-2.8% vs. -1.5%) and long-acting benzodiazepine (-3.7% vs. -3.5%) were observed in intervention group, but not statistically significant. None of the structural and organisational NH-related variables predicted either discontinuation or new-use of benzodiazepines; hospitalisations and initial use of meprobamate increased the likelihood of becoming a new-user of benzodiazepines. Multivariate analysis suggested that living in a particular NH could affect benzodiazepines discontinuation. CONCLUSIONS: A general intervention designed to improve overall NH quality indicators did not succeed in reducing benzodiazepines use. External factors interfered with the intervention. Further studies are needed to examine which NH-related aspects could impact benzodiazepines discontinuation.

How much exercise are older adults living in nursing homes doing in daily life? A cross-sectional study.

Information on the amount of exercise practised by nursing home (NH) residents is scarce. This study aimed at describing NH residents' participation in exercise classes, as well as to examine whether the presence of a professional exercise instructor in the facilities is associated with residents' exercise habits. The cross-sectional data of 5402 residents (median age = 88 years; mostly women (75.2%)) from 163 NHs in France were analysed. Adjusted logistic and linear regressions were performed to examine whether the presence of a professional exercise instructor in the NH was associated with exercise habits: exercise participation, frequency, duration, and levels. From the 5402 participants, 1914 were participating in exercise classes provided in the NH. Most of them had an exercise frequency of 1x/week or less. Median duration of exercise sessions was 45 min. Exercise levels were rated as: highly active (n = 487), intermediately active (n = 1096), and poorly active (n = 331). The presence of a professional exercise instructor working in the facility was significantly associated with exercise participation and with higher exercise frequencies and levels, and session duration. In conclusion, the presence of professional exercise instructors is associated with better exercise habits in NH residents. Improved exercise habits may potentially be translated into better health in this population.

Direct and indirect relationships between physical activity and happiness levels among older adults: a cross-sectional study.

OBJECTIVES: The purposes of this study were to examine if physical activity (PA) is associated to happiness and to investigate if social functioning and health status mediate this association. METHOD: Participants of this cross-sectional study were 323 men and women, age 60 or over, who were covered by the medical insurance of the French National Education System, France. They received by mail a self-report questionnaire that asked for information about general health, PA, and happiness. RESULTS: In multinomial logistic regressions, the total volume of PA was associated to higher levels of happiness, but this association disappeared in the presence of social functioning. A structural equation modelling (SEM) showed an indirect association between PA and happiness, which was mediated by participants' health status and social functioning; in this SEM model, social functioning was the only variable directly associated to happiness. CONCLUSION: Complex associations among PA, health status, and social functioning appear to determine happiness levels in older adults.

From rural to urban areas: differences in behavioural and psychological symptoms of dementia in nursing home residents according to geographical location.

BACKGROUND: We determined whether the prevalence of behavioural and psychological symptoms of dementia (BPSD) in institutionalized older adults differed according to the geographical location of different facilities. METHODS: This cross-sectional study covered 175 nursing homes (NH) in France (n = 6275; age, 86.0 ± 8.2 years; women, 73.7%). Information on NH residents' health status and NH structure and internal organization were recorded by the NH staff. Each participant was coded for the presence or absence of the following BPSD: aggressive, screaming, and wandering behaviours. NH were geographically defined as rural (<2000 inhabitants), low urban (2000 ≤ inhabitants < 10 000), intermediate urban (10 000 ≤ inhabitants < 100 000), or high urban (inhabitants ≥ 100 000). RESULTS: Adjusted binary logistic regressions showed that, compared with residents living in rural NH, those living in NH located in high-urban areas had a significantly higher risk of aggressiveness (odds ratio = 1.33; 95% confidence interval = 1.06-1.67) and screaming (odds ratio = 1.43; 95% confidence interval = 1.05-1.95). The likelihood of aggressiveness was also higher in residents living in NH located in intermediate-urban areas (odds ratio = 1.36; 95% confidence interval = 1.13-1.65). CONCLUSIONS: Rurality seems to play a positive role in the expression of BPSD. If this hypothesis were confirmed, it would encourage NH staff to develop activities that explore rural potentials for the management of BPSD.

Cross-sectional interactive associations of physical activity and sedentary behaviour with physical capacity across adulthood.

BACKGROUND: The way physical activity (PA) and sedentary behaviour (SB) independently and interactively modify the age-related decline in physical capacity remains poorly understood. This cross-sectional study investigated the independent and interactive associations of PA and SB with physical function and performance throughout the adult life course. METHODS: Data from 499 community-dwelling adults (63% female) aged 20-92 years, involved in the INSPIRE Human Translational Cohort, were used in this cross-sectional study. Daily time spent on moderate-to-vigorous PA (MVPA, min/day) and SB (h/day) was measured with activPAL triaxial accelerometers. Physical function and performance were assessed through the measurement of the 4-m usual gait speed (m/s), handgrip strength (kg), lower-limb strength (isokinetic knee extension torque, N·m), estimated lower-limb power (five-time chair-rise test performance, s) and cardiorespiratory fitness (V̇O2max, mL/kg/min). Confounder-adjusted multiple linear and curvilinear regressions were performed to investigate how MVPA, SB and their interactions were associated with the physical outcomes (all square root-transformed except gait speed) throughout the adulthood spectrum. RESULTS: Interaction analyses revealed that the combination of higher levels of MVPA with lower levels of SB favourably reshaped the negative relationship between handgrip strength and age (age2 × SB × MVPA: B = -7E-08, SE = 3E-08, P < 0.05). In addition, higher levels of MVPA were independently associated with an improved age-related profile in gait speed (age2 × MVPA: B = 3E-06, SE = 1E-06, P < 0.05), chair-rise performance (age × MVPA: B = -9E-05, SE = 4E-05, P < 0.05) and V̇O2max (MVPA at 21 years: B = 3E-02, SE = 7E-03, P < 0.05; age × MVPA: B = -5E-04, SE = 2E-04, P < 0.05). Conversely, the detrimental association of age with lower-limb muscle strength (age × SB: B = -1E-04, SE = 6E-05, P < 0.05) and chair-rise performance (age × SB: B = 1E-05, SE = 7E-06, P < 0.05) was exacerbated with increasing duration of SB, independently of MVPA. Supplementary analyses further revealed that some of these associations were age and sex specific. CONCLUSIONS: This cross-sectional study demonstrated that reduced sedentary time and increased activity duration were independently and synergistically associated with an attenuated age-related loss in physical capacity. These findings need to be confirmed with longitudinal data but encourage both adopting an active lifestyle and reducing sedentary time as preventive measures against physical aging.