Benjamin Seltzer

The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome

The objective of our study was to assess the efficacy and safety of donepezil in young adults with Down syndrome (DS) but no evidence of Alzheimer disease (AD). A 12‐week, randomized, double‐blind, placebo‐controlled study with a 12‐week, open‐label extension was conducted. The intervention consisted of donepezil (5–10 mg/day) in young adults (aged 18–35 years) with DS, but no AD. The primary measure was the Severe Impairment Battery (SIB) test and secondary measures were the Vineland Adaptive Behavior Scales (VABS), the Rivermead Behavioral Memory Test for Children, and the Clinical Evaluation of Language Fundamentals, Third Edition. At baseline, 123 subjects were randomly assigned treatment with donepezil or placebo. During the double‐blind phase, SIB scores improved significantly from baseline in both groups, with no significant between‐group differences. During the open‐label phase, SIB scores in the original donepezil group remained stable; the original placebo group showed an improvement similar to that seen in the double‐blind phase. VABS scores improved for donepezil, but not placebo, during the double‐blind phase (observed cases, P = 0.03; last observation carried forward, P = 0.07). Post hoc responder analyses were significant for donepezil using three of five response definitions (P ≤ 0.045). Adverse event rates were comparable to AD studies. In this first large‐scale, multicenter trial of a pharmacological agent for DS, donepezil appears safe. Efficacy interpretation was limited for the primary measure due to apparent learning/practice and ceiling effects. Outcomes in post hoc analyses suggested efficacy in some, but not all subjects, consistent with phenotypic variability of DS. Additional studies are required to confirm potential benefits of donepezil in this population.

Familial Dementia With Lewy Bodies With an Atypical Clinical Presentation

The authors report a case of a 64-year-old male with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB. (J Geriatr Psychiatry Neurol 2003; 16:59-64)

Unawareness of social interaction and emotional control deficits in alzheimer's disease

The purpose of this study was to examine unawareness of deficit in Alzheimers disease (AD) in a previously unexplored functional domain: social interaction and emotional control competency. Impairment of awareness was measured by calculating the degree to which patients and their caregivers disagreed on ratings of patient functioning. to assess potential underlying mechanisms or associated features of social/emotional unawareness, a regression equation examining disease and demographic correlates was created. In addition, to provide a basis of comparison for the social/emotional domain, unawareness of deficit was also assessed in two previously examined domains of functioning (i.e., cognitive and self-care competency). Results revealed that, as compared to caregivers, AD-diagnosed patients overestimated their social/emotional competency but to a lesser extent than they overestimated cognitive and self-care competencies. Regression analysis suggested that impaired awareness of social interaction and emotional control deficits was positively correlated with dementia severity and negatively correlated with education.

57 COGNITIVE FUNCTIONING AND CARDIOVASCULAR RISK: THE BOGALUSA HEART STUDY

Purpose of Study There is growing evidence that mid-life cardiovascular (CV) risk factors such as untreated hypertension, diabetes mellitus, hyperlipidemia and physical inactivity predispose people to various forms of late-life cognitive impairment, including Alzheimers disease. How early in life these factors begin to operate remains unknown. The Bogalusa Heart Study, an ongoing, long term community study of childhood and young adulthood CV risk factors in a biracial population, offers an ideal opportunity to examine the early antecedents of later life cognitive decline. Objective To examine the feasibility of evaluating cognitive function in the present middle-aged BHS cohort and its relation to present and early life CV risk factors. Methods Participants in the Bogalusa Heart Study, ages 24 to 44 years, were individually administered a battery of standard neuropsychological tests of verbal fluency, reading, digit span and similarities (Wechsler Adult Intelligence Scale), and the logical memory, verbal paired associates and visual reproduction tests from the Wechsler Memory Scale (third edition). Preliminary statistical correlations of test scores with various CV risk factors, e.g. systolic and diastolic blood pressure, were performed. Summary of Results The battery takes approximately 45 minutes to complete. Having flexible times to administer the battery was helpful in increasing enrollment. Participants were eager to participate. Although a few expressed some anxiety about their performance, all were able to complete the battery. Preliminary analysis of the correlations between the test results and CV risk data from the first 35 participants has allowed us to compute the power needed for a larger planned study. Conclusions The protocol is well received by participants, and a large scale study is feasible in the BHS cohort. Screening will continue until we obtain 100-120 participants. At that time we will examine correlations between test scores and CV risk factors and prepare a major proposal to examine the early CV risk factors that impact cognitive functioning in middle life.