The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer's disease.

OBJECTIVE: This study examined the association between a history of heavy alcohol use and smoking, presence of the apolipoprotein-E epsilon 4 allele (APOE epsilon4), and age of disease onset in a community dwelling sample of 685 Alzheimer's disease (AD) patients spanning three ethnic groups. DESIGN: Cross-sectional study of AD patients evaluated at a University-affiliated outpatient memory disorders clinic. SUBJECTS: A clinic-based cohort of white non-Hispanic (WNH; n = 397), white Hispanic (WH; n = 264), and African-American (AA; n = 24) patients diagnosed with possible or probable AD according to NINCDS-ADRDA diagnostic criteria. MEASUREMENTS: The age of onset of AD was obtained from a knowledgeable family member. All patients were assessed for APOE genotype. History of alcohol and tobacco consumption prior to the onset of dementia was obtained via an interview with the patient and the primary caregiver. A history of heavy drinking was defined as >2 drinks per day and a history of heavy smoking was defined as > or =1 pack per day. RESULTS: Presence of an APOE epsilon4 allele, a history of heavy drinking, or a history of heavy smoking were each associated with an earlier onset of AD by 2-3 years. Patients with all three risk factors were likely to be diagnosed with AD nearly 10 years earlier than those with none of the risk factors. CONCLUSION: The results suggest that APOE epsilon4 and heavy drinking and heavy smoking lower the age of onset for AD in an additive fashion.

Using different memory cutoffs to assess mild cognitive impairment.

OBJECTIVE: Although mild cognitive impairment (MCI) is characterized by performance on memory and other measures below expected normative values, neither a scientific rationale nor a consensus exists regarding which measures have the most use or the optimal cutoffs to use to establish impairment. METHODS: Different memory measures were administered to 80 normal community-dwelling subjects divided into two age groups. This provided conormed data on eight different memory indices by which to compare 23 nondemented clinically diagnosed patients with MCI who met all other criteria for Alzheimer disease (AD). RESULTS: On immediate memory for passages, delayed visual reproduction, object memory, and a measure sensitive to semantic interference, 70%-78% of patients with MCI were identified as impaired at 1.5 standard deviations or greater below expected levels. Conditional logistical regression for age-matched samples indicated that consideration of raw scores for these neuropsychologic tests in combination did not significantly change the odds of MCI diagnosis. When impairment relative to the total normal elderly sample was calculated based on one or more impairments at a 1.5 or greater cutoff, specificity fell below acceptable levels when more than three memory measures were considered. CONCLUSION: An array of widely used neuropsychologic measures demonstrated utility in distinguishing patients with MCI-AD from cognitively normal community-dwelling elders. The appropriateness of more or less stringent cutoffs was highly influenced by the number of measures considered. These findings have important implications regarding the choice of cut points for impairment used for the diagnosis of MCI in both research and clinical settings.

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies.

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.