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Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild–moderate Alzheimer’s disease (AD) has not been explored to date. Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild–moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs). The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild–moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant’s medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score ≥ 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline. Over half (55.7% [284/510]) of those with mild–moderate AD (age 72.8 ± 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (≥ 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11–1.19; p < 0.001), serious AEs (IRR 1.23; 95% CI 1.11–1.36; p < 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13–1.34; p < 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11–1.53; p < 0.001) and falls (IRR 1.20; 95% CI 1.03–1.42; p = 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression. In the current study, over half of older adults with mild–moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort.

Contains fulltext : 218263.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Benzodiazepines and related drugs (BDZRs) have been associated with an increased risk of Alzheimer's disease (AD) in later life. Despite this, it remains unclear whether ongoing BDZR use may further accelerate cognitive decline in those diagnosed with mild to moderate AD. DESIGN: This study was embedded within NILVAD, a randomized controlled trial of nilvadipine in mild to moderate AD. Cognition was measured at baseline and 18 months using the Alzheimer Disease Assessment Scale, Cognitive Subsection (ADAS-Cog). We assessed predictors of long-term BDZR use and analyzed the effect of ongoing BDZR use on ADAS-Cog scores at 18 months. Additionally, the impact of BDZR use on adverse events, incident delirium, and falls over 18-month follow-up was assessed adjusting for relevant covariates. SETTING AND PARTICIPANTS: 448 participants with mild to moderate AD recruited from 23 academic centers in 9 European countries. RESULTS: Overall, 14% (62/448) were prescribed an ongoing BDZR for the study duration. Increasing total number of (non-BDZR) medications was associated with a greater likelihood of BDZR prescription (odds ratio 1.16, 95% confidence interval 1.05-1.29). At 18 months, BDZR use was not associated with greater cognitive decline on the ADAS-Cog controlling for baseline ADAS-Cog scores, age, gender, study arm, and other clinical covariates (beta = 1.62, -1.34 to 4.56). However, ongoing BDZR use was associated with a greater likelihood of adverse events [incidence rate ratio (IRR) 1.19, 1.05-1.34], incident delirium (IRR 2.31, 1.45-3.68), and falls (IRR 1.66, 1.02-2.65) over 18 months that persisted after robust adjustment for covariates. CONCLUSIONS AND IMPLICATIONS: This study found no effect of ongoing BDZR use on ADAS-Cog scores in those with mild to moderate AD over 18 months. However, ongoing use of these medications was associated with an increased risk of adverse events, delirium, and falls. Thus, BDZR use should be avoided where possible and deprescribing interventions should be encouraged in older adults with AD.

Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4–74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4–72.0]), and 47 controls (69.4 years [95% CI, 68.3–70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity ( P =0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index ( P =0.011) and lower transfer function gain ( P =0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14–4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51–0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04–5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44–0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35–4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59–0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.