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ObjectiveTo determine whether orthostatic hypotension (OHYPO) and visit-to-visit blood pressure (BP) postural changes variability are associated with incident dementia.MethodsWe studied 2,131 older adults from the Health, Aging, and Body Composition cohort study. Orthostatic BP was repeatedly assessed over a 5-year baseline period. OHYPO was defined as a fall ≥15 mm Hg in systolic or ≥7 mm Hg in diastolic BP after standing from a sitting position for one-third or more of the visits. Systolic OHYPO and diastolic OHYPO were also examined separately. BP postural changes variability over time was evaluated with several indicators, including SD and coefficient of variation (CV). Incident dementia was determined over 12 years after the baseline period by dementia medication use, ≥1.5 SD decline in Modified Mini-Mental State Examination score, or hospitalization records.ResultsOf 2,131 participants (mean age 73 years, 53% female, 39% Black), 309 (14.5%) had OHYPO, 192 (9.0%) had systolic OHYPO, 132 (6.2%) had diastolic OHYPO, and 462 (21.7%) developed dementia. After adjustment for demographics, seated systolic BP (SBP), antihypertensive drugs, cerebrovascular disease, diabetes mellitus, depressive symptoms, smoking, alcohol, body mass index, and presence of 1 or 2 APOE ε4 alleles, systolic OHYPO was associated with greater dementia risk (adjusted hazard ratio [HR] 1.37, 95% confidence interval [CI] 1.01-1.88), unlike diastolic OHYPO and OHYPO. SBP postural changes variability was also associated with higher dementia risk (highest tertile of variability [CV]: adjusted HR 1.35, 95% CI 1.06-1.71).ConclusionSystolic OHYPO and visit-to-visit SBP postural changes variability were associated with greater dementia risk. Our findings raise the question of potential preventive interventions to control orthostatic SBP and its fluctuations.

Frailty is a clinical state reflecting a decrease in physiological reserve capacities, known to affect numerous biological pathways and is associated with health issues, including neurodegenerative diseases. However, how global protein expression is affected in the central nervous system in frail subject remains underexplored. In this post hoc cross‐sectional biomarker analysis, we included 90 adults (52–85 years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers of neurodegenerative diseases. We investigated the human proteomic profile of cerebrospinal fluid associated with frailty defined by an established cumulated frailty index (FI, average = 0.32), not enriched for neurology clinical features. Using a label‐free quantitative proteomic approach, we identified and quantified 999 proteins of which 13 were positively associated with frailty. Pathway analysis with the top positively frailty‐associated proteins revealed enrichment for proteins related to inflammation and immune response. Among the 60 proteins negatively associated with frailty, functional pathways enriched included neurogenesis, synaptogenesis and neuronal guidance. We constructed a frailty prediction model using ridge regression with 932 standardized proteins. Our results showed that the "proteomic model" could become an equivalent predictor of FI in order to study chronological age. This study represents the first comprehensive exploration of the proteomic profile of frailty within cerebrospinal fluid. It sheds light on the physiopathology of frailty, particularly highlighting processes of neuroinflammation and inhibition of neurogenesis. Our findings unveil a range of biological mechanisms that are dysregulated in frailty, in NPH subjects at risk of neurodegenerative impairment, offering new perspectives on frailty phenotyping and prediction. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether visit-to-visit blood pressure (BP) variability (BPV) is associated with incident frailty. We included 1 394 nonfrail community-dwelling participants aged ≥70 years from the Multidomain Alzheimer Preventive Trial (MAPT) who underwent repeated clinical examinations, including BP and frailty, over a 5-year follow-up period. Systolic BPV (SBPV), diastolic BPV (DBPV), mean arterial pressure variability (MAPV), and pulse pressure variability (PPV) were evaluated using standard deviation (SD), coefficient of variation (CV), average real variability, successive variation, variation independent of mean, and residual SD. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Higher SBPV was significantly associated with greater risk of frailty (1-SD increase of CV: hazard ratio [HR] = 1.18, 95% confidence interval [CI]: 1.02-1.36) after adjustment for demographics, systolic BP, antihypertensive drugs, body mass index, diabetes, ischemic heart disease, congestive heart failure, stroke, atrial fibrillation, MAPT randomization group, and frailty status. Similar results were observed with all indicators of variability. Higher PPV was associated with a greater risk of developing frailty over time (1-SD increase of CV: HR = 1.17, 95% CI: 1.01-1.35). DBPV and MAPV were not significantly associated with incident frailty. Higher SBPV and PPV were associated with greater risk of incident frailty. Our findings support the concept of BP physiological dysregulation underlying the frail state and suggest that BP instability could be an early marker of frailty. [ABSTRACT FROM AUTHOR]

Objectives: Pubmed literature search show that the prescription of potentially inappropriate medications is a major concern in older hospitalized patients, both from a clinical and financial perspective. This study aims to identify factors associated with exposure and potentially inappropriate medication costs in older hospitalized patients and to assess the financial impact of substituting these medications with safer alternatives. Methods: We performed an observational cross-sectional study of all patients aged 75 years or older hospitalized in a university hospital (except geriatric wards) on a given day. Potentially inappropriate medications were identified using European and French guidelines. Results: A total of 365 patients were included. At least one potentially inappropriate medication was prescribed in 50.4% of these patients. This contributed 19.7% [16.1; 23.6] to the average cost of medication per patient. Substitution of these medications with recommended alternatives was cost saving: average incremental cost per patient: -3.97 € [-7.21; -1.58]. Both polypharmacy and type of ward providing care were associated with increased costs of potentially inappropriate medications. Conclusions: This study assessed the prevalence of potentially inappropriate medications in older hospitalized patients and established that their substitution by alternative medications provided a cost saving. [ABSTRACT FROM AUTHOR]