ABSTRACT
BACKGROUND AND OBJECTIVE: Amnestic mild cognitive impairment (aMCI), characterized by episodic memory impairment in the absence of clinical dementia, often represents a transitional stage between normal aging and Alzheimer's disease (AD). It is not known if non-expert primary-care physicians (PCPs) can differentiate individuals with no cognitive impairment (NCI), aMCI and mild AD in a primary-care practice setting. This study develops an approach to this question, which is necessary for aMCI to become a treatment target. METHODS: Fourteen experts assessed subjects with memory complaints in terms of their laboratory test results, magnetic resonance imaging findings and scores on the Mini-Mental State Examination, adapted Clinical Dementia Rating Scale and Alzheimer's Disease Assessment Scale-cognitive subscale Delayed Word Recall before designating each subject as having NCI, aMCI or AD. Subjects agreed upon by a consensus committee were assigned to non-expert PCPs who, following brief training, assessed them using the same clinical information and utilizing the same assessment instruments. The chance-corrected inter-rater reliability (expert versus non-expert) measure κ, based on binary outcome (aMCI/not-aMCI), was estimated. RESULTS: The study recruited 119 evaluable subjects (50 aMCI, 27 mild AD and 42 NCI) and demonstrated fair to moderate agreement (κ = 0.423) between experts and non-experts in designation of aMCI. The percent agreement was 72.3%, sensitivity 62.0% and specificity 79.7%. Overall, non-experts under-rated the level of impairment compared with experts. CONCLUSION: This study established the feasibility of making the aMCI designation in the community and identified some likely sources of error. The results suggest that when drugs with clear benefit for aMCI patients are developed, community-based PCPs, with additional, more optimized training, will be able to accurately identify those patients who should receive treatment.
Subject(s)
Alzheimer Disease/diagnosis , Amnesia/diagnosis , Cognition Disorders/diagnosis , Feasibility Studies , Geriatric Assessment/methods , Primary Health Care/methods , Aged , Aged, 80 and over , Alzheimer Disease/complications , Amnesia/complications , Cognition Disorders/complications , Diagnostic Techniques and Procedures/instrumentation , Early Diagnosis , Female , Humans , Male , Middle Aged , Observer Variation , Psychiatric Status Rating Scales , Sensitivity and SpecificityABSTRACT
Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer's tolerate donepezil better than patients with MCI.
