Attention Measures of Accuracy, Variability, and Fatigue Detect Early Response to Donepezil in Alzheimer's Disease: A Randomized, Double-blind, Placebo-Controlled Pilot Trial.

OBJECTIVE: Donepezil is widely used to treat Alzheimer's disease (AD), but detecting early response remains challenging for clinicians. Acetylcholine is known to directly modulate attention, particularly under high cognitive conditions, but no studies to date test whether measures of attention under high load can detect early effects of donepezil. We hypothesized that load-dependent attention tasks are sensitive to short-term treatment effects of donepezil, while global and other domain-specific cognitive measures are not. METHOD: This longitudinal, randomized, double-blind, placebo-controlled pilot trial (ClinicalTrials.gov Identifier: NCT03073876) evaluated 23 participants newly diagnosed with AD initiating de novo donepezil treatment (5 mg). After baseline assessment, participants were randomized into Drug (n = 12) or Placebo (n = 11) groups, and retested after approximately 6 weeks. Cognitive assessment included: (a) attention tasks (Foreperiod Effect, Attentional Blink, and Covert Orienting tasks) measuring processing speed, top-down accuracy, orienting, intra-individual variability, and fatigue; (b) global measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, Dementia Rating Scale); and (c) domain-specific measures (memory, language, visuospatial, and executive function). RESULTS: The Drug but not the Placebo group showed benefits of treatment at high-load measures by preserving top-down accuracy, improving intra-individual variability, and averting fatigue. In contrast, other global or cognitive domain-specific measures could not detect treatment effects over the same treatment interval. CONCLUSIONS: The pilot-study suggests that attention measures targeting accuracy, variability, and fatigue under high-load conditions could be sensitive to short-term cholinergic treatment. Given the central role of acetylcholine in attentional function, load-dependent attentional measures may be valuable cognitive markers of early treatment response.

Therapy Update for Insomnia in the Elderly.

OBJECTIVE: To offer an update on insomnia in older adults and treatment options. DATA SOURCES: A search of PubMed using the terms "insomnia" and "older adults" was performed. Current guidelines, review articles, and drug database and manufacturer package inserts were utilized to provide relevant information. STUDY SELECTION: All English-language articles from 2012 to February 2017 and their bibliographies were reviewed for relevance. Current guidelines from the American College of Physicians, the American Academy of Sleep Medicine, and the American Geriatrics Society's Beers criteria were reviewed. DATA SYNTHESIS: Insomnia is a frequent complaint in the elderly. Treatment guidelines for this specific population are lacking. Anticholinergics, doxepin > 6 mg, benzodiazepines (BZDs), and non BZD receptor agonists (BzDRAs) are potentially inappropriate drugs for older adults. For adults with chronic insomnia, sleep hygiene practices and cognitive behavioral therapy should be considered as the initial treatments. If drug therapy is required or desired, the guidelines recommend short-term uses of BZDs (triazolam or temazepam), BzDRAs, low-dose doxepin (≤ 6 mg), ramelteon, or suvorexant. Risks and benefits of pharmacotherapy should be discussed with patients and caregivers prior to treatment initiation. Frequent and regular monitoring for adverse events is warranted to prevent detrimental outcomes. CONCLUSION: Nonpharmacologic interventions are the first-line therapy for adults with chronic insomnia. Short-term drug therapy may be considered as an alternative or add-on treatment. Hypnotic use is associated with harm and requires close monitoring, especially in older adults.

Smoking rates in dementia patients in the outpatient setting.

The purpose of this study is to determine the prevalence of tobacco use in patients diagnosed with dementia or cognitive impairment in an outpatient setting as they may be unsafe smokers and present safety risks to themselves and others. We conducted a retrospective chart review of new patients between 1/06 and 8/07 who were diagnosed with dementia or cognitive impairment in a geriatric outpatient practice. The data collected included age, gender, tobacco use patterns and mini-mental state examination (MMSE) score. Data was analyzed using SAS 9.1 for Windows (SAS Institute, Cary, NC). Former tobacco use rates in our study were similar to nationwide published rates for elderly over 65 (39.9% vs. 39.5%, respectively, p=0.99). However, only two patients in our study (1.32%, 95%CI=0.16-4.70) were current tobacco users compared with published census data that 10.2% of those over 65 are current smokers nationwide (p<0.001). Our study revealed a much lower rate of current tobacco use in our series of cognitively impaired patients. Further research is needed to explore the reasons for decreased smoking in those with cognitive impairment and its clinical implications.

Effects of graded levels of physical similarity and density on visual selective attention in patients with Alzheimer's disease.

A multitarget visual cancellation test was administered to patients with Alzheimer's disease (AD) and age-matched healthy controls (HC). Attentional loads--physical similarity (number of features shared by target and distractors; 3 levels) and density (number of items per page; 3 levels)--were varied systematically. As physical similarity increased, both groups slowed their search, but whereas the HC group maintained accuracy, the AD group increased commission errors and tended to miss more targets. Increased density yielded slower search and more target omissions in the AD group. Commission errors are additional indicators of higher order attentional deficits, especially in early disease. The findings suggest that patients with AD may rely increasingly on physical features of stimuli during a search, leading to inefficient bottom-up processing strategies.