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.

Epidemiology and long-term disease burden of herpes zoster and postherpetic neuralgia in Taiwan: a population-based, propensity score-matched cohort study.

BACKGROUND: The objectives of this study were to characterize the burden of herpes zoster, as well as the longitudinal and incremental changes of healthcare service utilization among individuals with herpes zoster and postherpetic neuralgia (PHN) compared to those without. METHODS: Using the National Health Insurance Research Database (NHIRD), we established a herpes zoster cohort of people diagnosed with herpes zoster between 2004 and 2008 as study cases. Another subset of the NHIRD, which was randomly selected from all elderly beneficiaries between 2004 and 2008 served as a non-herpes-zoster elderly control pool. Each case was then assigned one matched control according to age, gender, index date and propensity score. PHN cases were defined as those with persisting pain for more than 90 days after the onset of herpes zoster. RESULTS: Between 2004 and 2008, about 0.6 million patients were newly diagnosed with herpes zoster. The incidence increased with age, and most cases were identified during the summer period. Herpes zoster cases were found to have higher consumption of all types of healthcare services in the first year after the index date. Such increases were particularly obvious for patients with PHN, who showed incremental increases on average of 16.3 outpatient visits, 0.4 emergency room visits and 0.24 inpatient admissions per year. CONCLUSIONS: The incidence of herpes zoster increased with age and changed according to the seasons. Patients with herpes zoster were associated with higher healthcare utilization and this increase in healthcare utilization was most obvious for herpes zoster patients with PHN.

Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study.

BACKGROUND: Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. METHODS: We used Taiwan's Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. RESULTS: The study cohort comprised 59,042 older adults (65-74 yr: 39,358 [66.7%], 75-84 yr: 16,903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65-74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10-2.19), then among those aged 75-84 yr (+1.79, 95% CI 1.70-1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36-1.05). The number of potentially inappropriate medications increased among patients aged 65-74 years (+0.16 [0.15-0.18]) and 75-84 years (+0.09 [0.06-0.08]), but decreased in those aged 85 years and older (-0.15 [-0.26 to -0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5-9 drugs: odds ratio [OR] 1.18, 95% CI 1.12-1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42-1.66) and anticholinergic burden (score 1-2: 1.39, 95% CI 1.31-1.48; ≥ 3: 1.53, 95% CI 1.41-1.66) showed dose-response relations with fracture-specific admission to hospital. INTERPRETATION: The total number of drugs taken (polypharmacy), number of potentially inappropriate medications and anticholinergic risk changed during follow-up and varied across age groups in this cohort of older adult patients. These indicators showed dose-response relations with admission to hospital, but not with death.

Safeguarding vitality and cognition: The role of sarcopenia in intrinsic capacity decline among octogenarians from multiple cohorts.

BACKGROUND: Sarcopenia and intrinsic capacity (IC) declines pose significant challenges to healthy aging, particularly in the rapidly growing octogenarian population. This study aimed to elucidate the relationship between sarcopenia and declines in IC across multiple cohorts of community-dwelling older adults. METHODS: Data from four Taiwanese cohorts were analyzed. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria (algorithm 1: categorized as either having possible sarcopenia or not (robust); algorithm 2: categorized as robust, possible sarcopenia or sarcopenia). IC was operationalized using the World Health Organization's Integrated Care for Older People (ICOPE) framework (step 1 and step 2), encompassing six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being. Multivariable logistic regression models were adopted to assess the association between sarcopenia and IC decline. RESULTS: Among 599 octogenarians (median age 82.2 years, 54.8% male), the prevalence of possible sarcopenia (algorithm 1) was 64.6%. When adopting algorithm 2, the prevalence of possible sarcopenia and sarcopenia was 46,2% and 32.1%, respectively. After adjusting for covariates, participants with possible sarcopenia or sarcopenia (algorithm 2) were more likely to exhibit declines in vitality (ICOPE Step 1: possible sarcopenia aOR 3.65, sarcopenia aOR 4.74; ICOPE Step 2: possible sarcopenia aOR 5.11, sarcopenia aOR 14.77) and cognition (ICOPE Step 1: possible sarcopenia aOR 2.40, sarcopenia aOR 2.12; ICOPE Step 2: possible sarcopenia aOR 2.02, sarcopenia aOR 2.51) compared to robust individuals. CONCLUSIONS: This study underscores the robust association between sarcopenia and declines in vitality and cognition among octogenarians, highlighting the importance of sarcopenia screening and management in promoting healthy longevity in this vulnerable population.

Association of intrinsic capacity with functional decline and mortality in older adults: a systematic review and meta-analysis of longitudinal studies.

BACKGROUND: Together with environmental factors, intrinsic capacity (the composite of all the physical and mental capacities of an individual) has been proposed as a marker of healthy ageing. However, whether intrinsic capacity predicts major clinical outcomes is unclear. We aimed to explore the association of intrinsic capacity with functional decline and mortality in older adults. METHODS: In this systematic review and meta-analysis, we conducted a systematic search in MEDLINE (via PubMed), Scopus, and Web of Science from database inception to Feb 14, 2024, of observational longitudinal studies conducted in older adults (age ≥60 years) assessing the association of intrinsic capacity with impairment in basic activities of daily living (BADL) or instrumental activities of daily living (IADL) or risk of mortality. Estimates were extracted by two reviewers (JLS-S and W-HL) and were pooled using three-level meta-analytic models. The quality of each study was independently assessed by two authors (JLS-S and PLV) using the Newcastle-Ottawa Scale for longitudinal studies. Heterogeneity was evaluated using the I2 indicator at two levels: within-study (level 2) and between-study (level 3) variation. For associations between intrinsic capacity and IADL and BADL, we transformed data (standardised ß coefficients and odds ratios [ORs]) into Pearson product moment correlation coefficients (r) using Pearson and Digby formulas to allow comparability across studies. For associations between intrinsic capacity and risk of mortality, hazard ratios (HRs) with 95% CIs were extracted from survival analyses. This study is registered with PROSPERO, CRD42023460482. FINDINGS: We included 37 studies (206 693 participants; average age range 65·3-85·9 years) in the systematic review, of which 31 were included in the meta-analysis on the association between intrinsic capacity and outcomes; three studies (2935 participants) were included in the meta-analysis on the association between intrinsic capacity trajectories and longitudinal changes in BADL or IADL. Intrinsic capacity was inversely associated with longitudinal impairments in BADL (Pearson's r -0·12 [95% CI -0·19 to -0·04]) and IADL (-0·24 [-0·35 to -0·13]), as well as with mortality risk (hazard ratio 0·57 [95% CI 0·51 to 0·63]). An association was also found between intrinsic capacity trajectories and impairment in IADL (but not in BADL), with maintained or improved intrinsic capacity over time associated with a lower impairment in IADL (odds ratio 0·37 [95% CI 0·19 to 0·71]). There was no evidence of publication bias (Egger's test p>0·05) and there was low between-study heterogeneity (I2=18·4%), though within-study (I2=63·2%) heterogeneity was substantial. INTERPRETATION: Intrinsic capacity is inversely associated with functional decline and mortality risk in older adults. These findings could support the use of intrinsic capacity as a marker of healthy ageing, although further research is needed to refine the structure and operationalisation of this construct across settings and populations. FUNDING: None. TRANSLATIONS: For the Spanish and French translations of the abstract see Supplementary Materials section.

Integrative Multimodal Metabolomics to Early Predict Cognitive Decline Among Amyloid Positive Community-Dwelling Older Adults.

Alzheimer's disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals who progressed to cognitive decline from those who remained cognitively intact. A plasma-derived metabolite signature was developed from Supercritical Fluid chromatography coupled with high-resolution mass spectrometry (SFC-HRMS) and nuclear magnetic resonance (NMR) metabolomics. The 2 metabolomics data sets were analyzed by Data Integration Analysis for Biomarker discovery using Latent approaches for Omics studies (DIABLO), to identify a minimum set of metabolites that could describe cognitive decline status. NMR or SFC-HRMS data alone cannot predict cognitive decline. However, among the 320 metabolites identified, a statistical method that integrated the 2 data sets enabled the identification of a minimal signature of 9 metabolites (3-hydroxybutyrate, citrate, succinate, acetone, methionine, glucose, serine, sphingomyelin d18:1/C26:0 and triglyceride C48:3) with a statistically significant ability to predict cognitive decline more than 3 years before decline. This metabolic fingerprint obtained during this exploratory study may help to predict amyloid-positive individuals who will develop cognitive decline. Due to the high prevalence of brain amyloid-positivity in older adults, identifying adults who will have cognitive decline will enable the development of personalized and early interventions.

Reference centiles for intrinsic capacity throughout adulthood and their association with clinical outcomes: a cross-sectional analysis from the INSPIRE-T cohort.

Intrinsic capacity (IC), a function-centered construct, is defined as the composite of all physical and mental capacities of an individual. IC and surrounding environmental factors determine an individual's functional ability to do what they want or feel valued. Current literature lacks evidence on how IC varies throughout adulthood. In this study, we demonstrated a method to establish age-specific and sex-specific reference centiles for IC using the Human Translational Research Cohort of the INSPIRE Platform (975 adults, aged 20-102 years, living in the southwest France, Toulouse area). IC was operationalized as the mean score of the five key domains (cognition, locomotion, psychology, sensory and vitality) and the factor score from a bifactor model, respectively. Both IC operationalizations showed higher IC levels in young and middle age and markedly lower levels after age 65 years, with greater inter-individual variation in old age than in youth. Individuals with IC ≤10th percentile tended to have high comorbidity, prefrailty/frailty, difficulties in basic and instrumental activities of daily living and falls than individuals with IC >90th percentile. These findings suggest that IC reference centiles can help monitor the functional capacity of individuals during aging, similar to tracking children's development with growth charts.

Plasma inflammation-related biomarkers are associated with intrinsic capacity in community-dwelling older adults.

BACKGROUND: How inflammation relates to intrinsic capacity (IC), the composite of physical and mental capacities, remains undefined. Our study aimed to investigate the cross-sectional and longitudinal associations between plasma inflammation-related biomarkers and IC in older adults. METHODS: This secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT) included 1238 community-dwelling older individuals with IC assessments from 12 to 60 months. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor receptor-1 (TNFR-1), monocyte chemoattractant protein-1 (MCP-1) and growth differentiation factor-15 (GDF-15) were measured at 12 months. IC was operationalized as a score ranging from 0 to 100, derived from four domains: cognition, Mini-Mental State Examination; locomotion, Short Physical Performance Battery; psychological, Geriatric Depression Scale; and vitality, handgrip strength. A five-domain IC score (plus sensory) was investigated in a subsample (n = 535) with a 1-year follow-up as an exploratory outcome. RESULTS: The mean age of the 1238 participants was 76.2 years (SD = 4.3); 63.7% were female. Their initial four-domain IC scores averaged 78.9 points (SD = 9.3), with a yearly decline of 1.17 points (95% CI = -1.30 to -1.05; P < 0.001). We observed significant associations of lower baseline IC with higher CRP, IL-6, TNFR-1 and GDF-15, after controlling age, sex, MAPT group allocation and educational level [CRP: adjusted ß (95% CI) = -1.56 (-2.64 to -0.48); P = 0.005; IL-6: adjusted ß = -3.16 (-4.82 to -1.50); P < 0.001; TNFR-1: adjusted ß = -6.86 (-10.25 to -3.47); P < 0.001; GDF-15: adjusted ß = -7.07 (-10.02 to -4.12); P < 0.001]. Higher TNFR-1, MCP-1 and GDF-15 were associated with faster decline in four-domain IC over 4 years [TNFR-1: adjusted ß (95% CI) = -1.28 (-2.29 to -0.27); P = 0.013; MCP-1: adjusted ß = -1.33 (-2.24 to -0.42); P = 0.004; GDF-15: adjusted ß = -1.42 (-2.26 to -0.58); P = 0.001]. None of the biomarkers was significantly associated with the five-domain IC decline. CONCLUSIONS: Inflammation was associated with lower IC in older adults. Among all plasma biomarkers, TNFR-1 and GDF-15 were consistently associated with IC at the cross-sectional and longitudinal levels.

Multi-Trajectories of Intrinsic Capacity Decline and Their Impact on Age-Related Outcomes: A 20-Year National Longitudinal Cohort Study.

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p>0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p>0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p>.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well.

Association between aging-related biomarkers and longitudinal trajectories of intrinsic capacity in older adults.

Intrinsic capacity (IC), the composite of physical and mental capacities, declines with age at different rates and patterns between individuals. We aimed to investigate the association between longitudinal IC trajectories and plasma biomarkers of two hallmarks of aging-chronic inflammation and mitochondrial dysfunction-in older adults. From the Multidomain Alzheimer Preventive Trial (MAPT), we included 1271 community-dwelling older people (mean [SD] age = 76.0 [4.3] years) with IC data over four years. Group-based multi-trajectory modeling was performed to identify clusters of the participants with similar longitudinal patterns across four IC domains: cognition, locomotion, psychology, and vitality. Five IC multi-trajectory groups were determined: low in all domains (8.4%), low locomotion (24.6%), low psychological domain (16.7%), robust (i.e., high in all domains except vitality; 28.3%), and robust with high vitality (22.0%). Compared to the best trajectory group (i.e., robust with high vitality), elevated levels of plasma interleukin-6 (IL-6), tumor necrosis factor receptor-1 (TNFR-1), and growth differentiation factor-15 (GDF-15) were associated with a higher risk of belonging to the "low in all domains" group (IL-6: relative risk ratio (RRR) [95% CI] = 1.42 [1.07 - 1.88]; TNFR-1: RRR = 1.46 [1.09 - 1.96]; GDF-15: RRR = 1.99 [1.45 - 2.73]). Higher IL-6 and GDF-15 also increased the risk of being in the "low locomotion" group. GDF-15 outperformed other biomarkers by showing the strongest associations with IC trajectory groups. Our findings found that plasma biomarkers reflecting inflammation and mitochondrial impairment distinguished older people with multi-impaired IC trajectories from those with high-stable IC.

Associations of plasma neurofilament light chain and progranulin with frailty in older adults.

BACKGROUND: In previous studies, plasma neurofilament light chain (NfL) and progranulin (PGRN) levels are associated with cognitive and physical impairment in older individuals. However, evidence of their relationships with frailty is lacking. This study aims to explore the associations of plasma NfL and PGRN levels with frailty in community-dwelling older adults. METHODS: We included 507 older adults (mean [standard deviation] age, 76.7 [4.5] years) with plasma NfL and PGRN measurements from the Multidomain Alzheimer Preventive Trial (MAPT). The timepoint of biomarker measurements, either 12 or 24 months after study enrollment, was defined as the baseline for each participant. Frailty phenotype (robust, pre-frail, and frail) was assessed at 12, 24, 36, 48, and 60 months by Fried's frailty criteria. The cross-sectional associations between plasma neurodegenerative biomarkers and frailty severity were examined using logistic regressions. We further used Cox proportional hazard models to evaluate the associations between plasma biomarkers and incident frailty among robust or pre-frail participants at baseline (n = 403). RESULTS: At baseline, participants with high plasma NfL levels (>93.11 pg/ml [the upper quartile]) had a higher likelihood of pre-frailty or frailty compared to their normal NfL counterparts (odds ratio = 1.68; 95% confidence interval = 1.10-2.57); however, this association did not remain significant after controlling for covariates. Neither NfL nor PGRN levels showed prospective associations with incident frailty over 4 years. CONCLUSIONS: This study failed to find associations of circulating NfL and PGRN levels with frailty among community-dwelling older adults in adjusted analyses. Whether plasma neurodegenerative markers serve as potential biomarkers of frailty requires further investigation.

Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults.

We investigated combining a core AD neuropathology measure (plasma amyloid-beta [Aß] 42/40) with five plasma markers of inflammation, cellular stress, and neurodegeneration to predict cognitive decline. Among 401 participants free of dementia (median [IQR] age, 76 [73-80] years) from the Multidomain Alzheimer Preventive Trial (MAPT), 28 (7.0%) participants developed dementia, and 137 (34.2%) had worsening of clinical dementia rating (CDR) scale over 4 years. In the models utilizing plasma Aß alone, a tenfold increased risk of incident dementia (nonsignificant) and a fivefold increased risk of worsening CDR were observed as each nature log unit increased in plasma Aß levels. Models incorporating Aß plus multiple plasma biomarkers performed similarly to models included Aß alone in predicting dementia and CDR progression. However, improving Aß model performance for composite cognitive score (CCS) decline, a proxy of dementia, was observed after including plasma monocyte chemoattractant protein 1 (MCP1) and growth differentiation factor 15 (GDF15) as covariates. Participants with abnormal Aß, GDF15, and MCP1 presented higher CCS decline (worsening cognitive function) compared to their normal-biomarker counterparts (adjusted ß [95% CI], - 0.21 [- 0.35 to - 0.06], p = 0.005). In conclusion, our study found limited added values of multi-biomarkers beyond the basic Aß models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with Aß pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance.

Associations Between Nutritional Deficits and Physical Performance in Community-Dwelling Older Adults.

Background: Whether multiple nutritional deficiencies have a synergic effect on mobility loss remains unknown. This study aims to evaluate associations between multi-nutritional deficits and physical performance evolution among community-dwelling older adults. Methods: We included 386 participants from the Multidomain Alzheimer Preventive Trial (MAPT) (75.6 ± 4.5 years) not receiving omega-3 polyunsaturated fatty acid (PUFA) supplementation and who had available data on nutritional deficits. Baseline nutritional deficits were defined as plasma 25 hydroxyvitamin D <20 ng/ml, plasma homocysteine >14 µmol/L, or erythrocyte omega-3 PUFA index ≤ 4.87% (lower quartile). The Short Physical Performance Battery (SPPB), gait speed, and chair rise time were used to assess physical performance at baseline and after 6, 12, 24, 36, 48, and 60 months. We explored if nutrition-physical performance associations varied according to the presence of low-grade inflammation (LGI) and brain imaging indicators. Results: Within-group comparisons showed that physical function (decreased SPPB and gait speed, increased chair rise time) worsened over time, particularly in participants with ≥2 nutritional deficits; however, no between-group differences were observed when individuals without deficit and those with either 1 or ≥2 deficits were compared. Our exploratory analysis on nutritional deficit-LGI interactions showed that, among people with ≥2 deficits, chair rise time was increased over time in participants with LGI (adjusted mean difference: 3.47; 95% CI: 1.03, 5.91; p = 0.017), compared with individuals with no LGI. Conclusions: Accumulated deficits on vitamin D, homocysteine, and omega-3 PUFA were not associated with physical performance evolution in older adults, but they determined declined chair rise performance in subjects with low-grade inflammation. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT00672685], identifier [NCT00672685].

Impact of Multiple Prescriptions With Anticholinergic Properties on Adverse Clinical Outcomes in the Elderly: A Longitudinal Cohort Study in Taiwan.

The cumulative effect of multiple pharmaceutics with anticholinergic properties (i.e., anticholinergic burden), can serve as an indicator of suboptimal prescribing in the elderly. Yet, no research is available concerning the effect of different compositions of score on adverse outcomes under the same anticholinergic burden. This population-based cohort study investigated whether different combinations of medications with anticholinergic properties have different impacts on adverse outcomes in the elderly using the Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden Scale (ACB) scores. We included 116,043 people aged 65 years and older from Taiwan's Longitudinal Health Insurance Database and measured their monthly anticholinergic burden over a 10-year follow-up period (from January 1, 2002, to December 31, 2011). We analyzed the association between different anticholinergic score compositions and adverse outcomes (emergency department visits, all-cause hospitalizations, fracture-specific hospitalizations, and incident dementia) via generalized estimating equations. Cumulative effects of multiple medications with low anticholinergic activity were associated with a greater risk for emergency department visits and all-cause hospitalizations (emergency department visits for 65-74 year olds (y/o): ACB 1 + 1 + 1, adjusted odds ratio (aOR) 2.05 (1.99-2.12); ACB 1 + 2, aOR 2.04 (1.91-2.17); and ACB 3, aOR 1.62 (1.57-1.66)). In contrast, using medications with greater potency had a greater impact on central adverse outcomes (incident dementia for 65-74 y/o: ACB 1 + 1 + 1, aOR 3.30 (2.84-3.84); ACB 1 + 2, aOR 5.84 (4.59-7.41); and ACB 3, aOR 9.15 (8.38-9.99)). The quantity of anticholinergics (even with low score) an older person used matters in risk of emergency department visit and all-cause hospitalization but the potency of anticholinergics (i.e., those with high score) matters in risk of fracture-specific hospitalization and incident dementia.

Biological and Neuroimaging Markers as Predictors of 5-Year Incident Frailty in Older Adults: A Secondary Analysis of the MAPT Study.

BACKGROUND: This study aims to investigate the predictive value of biological and neuroimaging markers to determine incident frailty among older people for a period of 5 years. METHODS: We included 1394 adults aged 70 years and older from the Multidomain Alzheimer Preventive Trial, who were not frail at baseline (according to Fried's criteria) and who had at least 1 post-baseline measurement of frailty. Participants who progressed to frailty during the 5-year follow-up were categorized as "incident frailty" and those who remained non-frail were categorized as "without frailty." The differences of baseline biochemical factors (25-hydroxyvitamin D, homocysteine, omega-3 index, C-reactive protein), other biological markers (Apolipoprotein E genotypes, amyloid-ß deposits), and neuroimaging data (gray matter volume, hippocampal volume, white matter hyperintensities) were compared between groups. Cox proportional hazard model was used to evaluate the associations between biomarkers and incident frailty. RESULTS: A total of 195 participants (14.0%) became frail over 5 years. Although 25-hydroxyvitamin D deficiency, homocysteine levels, low-grade inflammation (persistently increased C-reactive protein 3-10 mg/L), gray matter, and hippocampal volume were significantly associated with incident frailty in unadjusted models, these associations disappeared after adjustment for age, sex, and other confounders. Omega-3 index was the sole marker that presented a trend of association with incident frailty (hazard ratio: 0.92; 95% confidence interval: 0.83-1.01; p = .082). CONCLUSIONS: This study failed to identify biomarkers able to predict frailty incidence in community-dwelling older adults for a period of 5 years. Further longitudinal research with multiple measurements of biomarkers and frailty is needed to evaluate the long-term relationships between changes in biomarkers levels and frailty evolution.

Cross-sectional and prospective associations between cerebral cortical thickness and frailty in older adults.

BACKGROUND: Several neurodegenerative markers measured by magnetic resonance imaging (MRI) have shown to be related with frailty. While most studies have focused on surrogates of cerebral vascular damage such as increased white matter lesions, the associations between cortical atrophy and frailty were less often investigated. OBJECTIVES: To investigate the cross-sectional and prospective associations between cortical thickness and frailty evolution in older adults. METHODS: We enrolled 484 community-dwelling adults aged ≥70 years, participants from the Multidomain Alzheimer Preventive Trial (MAPT), with data on cerebral cortical thickness and frailty. Cortical thickness was acquired by MRI for whole-brain and regional cortices. Two function-specific regions of interest, i.e., mobility-related regions and Alzheimer's disease (AD) signature, were selected on the basis of previous studies. Frailty status was assessed by the Fried frailty phenotype (i.e., weakness, slowness, involuntary weight loss, fatigue and low physical activity level) at baseline, after 6 months and every year until the end of the 5-year follow-up. RESULTS: Older adults with higher global cortical thickness were less likely to be pre-frail and frail at baseline (adjusted OR: 0.13, 95% CI: 0.03-0.65, p = 0.013). In addition, higher cortical thickness in mobility-related and AD-signature regions were associated with lower likelihood of being pre-frail and frail. Similar associations were observed for having weakness and slowness. However, neither global nor region-specific cortical thickness showed prospective associations with future frailty onset. CONCLUSIONS: The global and regional cortical thickness cross-sectionally associated with frailty in older adults, but no prospective associations with incident frailty were found. The longitudinal relationship between cortical thickness and frailty evolution requires further investigation.

Post-acute care regains quality of life among middle-aged and older stroke patients in Taiwan.

OBJECTIVE: This study aims to evaluate health-related quality of life (HRQoL) of middle-aged and older stroke patients receiving the stroke post care (PAC) program and to identify possible predictors. DESIGN, SETTING AND PARTICIPANTS: This is a retrospective cohort study. Demographic characteristics and functional outcomes (modified Rankin Scale, Barthel Index, Mini-Mental State Examination, and the Concise Chinese Aphasia Test) were collected at enrollment. EQ-5D HRQoL questionnaires were administered at the beginning and the end of PAC, and health state utilities were compared. RESULTS: The EQ-5D utilities of stroke patients aged 75-84 years and 85 years or above were estimated to be 0.091 and 0.159 lower than those aged less than 50 years. A decrease of the utility by 0.075 was observed among patients with the prior history of stroke. The EQ-5D utilities of patients having Barthel Index of 21-40, 41-60, and 61-100 were 0.1432, 0.1568, and 0.1387 higher than those having Barthel Index of 0-20, respectively. For patients reporting extreme problems in self-care or any dimension of EQ-5D questionnaires prior to PAC, increases in utilities by 0.0733 and 0.2875 were noted. The EQ-5D utility of PAC service duration rose by 0.0733 per one incremental day. CONCLUSIONS AND IMPLICATIONS: This study provides vital evidence regarding time-varying benefits of PAC services to HRQoL of stroke patients and to identify multiple predictors of HRQoL among stroke patients receiving PAC services. This study thus could serve as good reference to enhance quality of PAC services among stroke patients.