Potentially inappropriate medication use in older adults with mild-moderate Alzheimer's disease:Prevalence and associations with adverse events

Aim: Potentially inappropriate medication (PIM) use is prevalent in older adults and is associated with adverse events, hospitalisation and mortality. We assessed the patterns and associations of PIM use in older adults with mild-to-moderate Alzheimer's Disease (AD), who may represent a particularly vulnerable group. Design: Analysis of data from NILVad, an 18-month Randomised Control Trial of Nilvadapine in mild-to-moderate AD. The v2 STOPP criteria were applied in duplicate to identify PIM use. Associations between PIM use and adverse events/unscheduled healthcare visits in addition to the associations between PIM use and AD progression were evaluated. Setting and Participants: 448 older adults with mild-to-moderate AD from 23 centres in nine European countries. Results: Of 448 participants (mean age: 72.56 ± 8.19 years), over half (55.8%) were prescribed a PIM with 30.1% being prescribed 2+ PIMs. The most frequent PIMs were (i) long-term benzodiazepines (11.6% N = 52/448), (ii) selective serotonin reuptake inhibitors without appropriate indication (11.1% N = 50/448), and (iii) Proton-Pump Inhibitors (PPIs) without appropriate indication (10.7% N = 48/448). Increasing number of PIMs was associated with a greater risk of adverse events (IRR 1.17, 1.13-1.19, P < 0.001), serious adverse events (IRR 1.27; 1.17-1.37, P < 0.001), unscheduled hospitalisations (IRR 1.16, 1.03-1.30, P = 0.016) and GP visits (IRR 1.22, 1.15-1.28, P < 0.001). PIM use was not associated with dementia progression. Conclusions and Implications: PIM use is highly prevalent in mild-to-moderate AD and is associated with adverse events and unscheduled healthcare utilisation. Further attention to de-prescribing in this vulnerable group is warranted

The role of SOAT-1 polymorphisms in cognitive decline and delirium after bypass heart surgery

Our study confirmed the expected cognitive decline and highly frequent delirium after bypass heart surgery and excluded the possible role of SOAT-1 genotype polymorphisms in their genesis

The role of apolipoprotein E in cognitive decline and delirium after bypass heart operations

Cognitive decline and delirium are common complications after heart bypass surgery. Based on the reported role of the APOE-epsilon 4 allele in neurodegenerative diseases, we studied its association with these complications. A neuropsychological test battery consisting of the Mini Mental State Examination, the Wechsler's Memory Scale Revised, the Brief Psychiatric Rating Scale, and the Delirium Rating Scale was applied to 137 APOE-genotyped patients on admission and 1 month after bypass surgery. We correlated the APOE (apolipoprotein E) polymorphism with the postoperative test outcome by taking into account all factors known to influence cognitive capacity after heart surgery. There was a significant decline in all test results 1 month after surgery and a high frequency of postoperative delirium. Neither this decline nor the frequency of delirium was associated with the APOE-epsilon 4 allele. This study confirms the high incidence of cognitive decline and delirium after coronary surgery, but it does not support the role of the APOE-epsilon 4 allele in the occurrence of these complications

Antidepressant Use and Orthostatic Hypotension in Older Adults Living with Mild-to-Moderate Alzheimer Disease

Objectives: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. Methods: We performed a cross-sectional analysis of baseline data from the NILVAD study. Participants with mild-moderate AD were recruited from 23 centres in 9 countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 & 5 minutes of standing. OH was defined as a drop of 6520 mmHg SBP/ 65 10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. Results: Of 509 participants (72.9 \ub1 8.3 years, 61.9% female), two-fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (\u3b2: 1.83, 0.16-3.50, P = 0.03 for SBP; \u3b2: 1.13, 0.02-2.25, P < 0.05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1-3.6, P = 0.02). Both findings persisted following robust covariate adjustment. Conclusions: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort. This article is protected by copyright. All rights reserved

Sedative Load in Community-Dwelling Older Adults with Mild-Moderate Alzheimer's Disease: Longitudinal Relationships with Adverse Events, Delirium and Falls

Background 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. Objectives 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). Methods 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. Results 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. Conclusions 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