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Within the context of early diagnosis of Alzheimer's disease (AD), there is a growing interest in neuropsychological screening tests. Amongst these tests, we focused on the largely used Memory Impairment Screen (MIS). The objective of the present work was to show that adding a 10-min delayed recall to the MIS, improves the test psychometric characteristics in order to detect dementia in the earliest stages. A prospective study was carried out on a cohort of 270 consecutive elderly ambulatory subjects attending the Broca Hospital Memory Clinic: normal controls (n = 67), mild cognitive impairment subjects (n = 98) and mildly demented patients [n = 105, Mini Mental State Examination (MMSE) = 23 +/- 4]. This study consisted in testing the advantage of the 10-min delayed recall entitled MIS-D compared with the MIS. At a cut-off score of 6, the MIS-D revealed satisfying psychometric characteristics with a sensitivity of 81% and a specificity of 91%, whilst the MIS alone indicated a sensitivity of 60% and a specificity of 88% in detecting dementia. In demented patients with MMSE score > or =26, MIS-D properties still remained satisfying (sensitivity: 75%, specificity: 92%). MIS-D is a more relevant screening test than MIS alone at very early stages of dementia.

The objective of our study was to evaluate the effects of the apolipoprotein E (ApoE) phenotype and gender on the response to tacrine treatment in Alzheimer's disease (AD). ApoE phenotyping was performed on 76 patients treated with tacrine for AD. This group comprised 33 ApoE epsilon4 allele carriers (epsilon4+) and 43 non-epsilon4 carriers (epsilon4-). Patients were treated blindly in relation to the ApoE phenotype, with incremental tacrine dosages ranging from 40 mg/day up to the highest dosage (160 mg) tolerated without side-effects. At least 6 weeks elapsed between each increase. Changes in the scores for the Alzheimer Disease Assessment Scale-Cognitive Component (ADAS-Cog) between baseline and each increment in dosage were assessed in the epsilon4- and epsilon4+ groups. The cut-off point for being considered as responsive to tacrine treatment was a 4-point decrease in the ADAS-Cog score. There was no tendency for the epsilon4- carriers to respond better than the epsilon4+ carriers. When patients were stratified by gender, no differences were found between the effects of the treatment on men and women. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to tacrine in AD patients.

Controversy exists regarding the apolipoprotein E (ApoE) epsilon4 allele association with vascular dementia (VaD), ranging from increased epsilon4 frequency, similar to that found for Alzheimer's disease (AD), to no association between the epsilon4 allele and VaD. To clarify further the relationship between ApoE alleles polymorphism and cerebrovascular disease (CVD) in demented and cognitively impaired patients, we examined the ApoE phenotypes in a sample of 280 patients: 155 with AD, 21 with VaD, 32 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) but without CVD, and 27 in which vascular disease was the most probable cause of cognitive decline [vascular mild cognitive impairment (VMCI)]. Our results show that the frequency of the ApoE epsilon4 allele in patients over 70 years old with clinically diagnosed VaD and VMCI does not differ significantly from that of controls. In contrast, ApoE epsilon4 allele-bearing individuals had greater risk of having late-onset AD (OR = 8.8; 95% CI 3.7-21.0), or non-vascular cognitive impairment (OR = 7.0; 95% CI 2.5-19.0)., (Copyright 1999 Lippincott Williams & Wilkins)

The efficacy of tacrine in the treatment of patients with probable Alzheimer's disease (AD) was evaluated in a double-blind, placebo-controlled, enriched population multicenter study in France. A total of 280 patients entered the dose titration phase of the study. The assessment of potential benefit of tacrine ("best dose") was based on demonstrating improvement on the Alzheimer's Disease Assessment Scale (ADAS) total score versus a blinded placebo. One hundred and thirty of 242 (54%) patients achieved a "best dose" and were eligible for the double-blind, parallel group (pivotal) phase. Primary efficacy measures were ADAS-Cognitive and Clinical Global Impression of Change; secondary efficacy measures of cognition and activities of daily living were also included. Results indicated that tacrine-treated patients showed improved functioning based on the ADAS-Cognitive in comparison to placebo-treated patients. Transaminase elevations above the upper limit of normal occurred in 32% of patients, were more frequent in women than in men, demonstrated a delayed onset, and returned to normal limits for all patients following discontinuation of treatment The results from this study are supportive of the efficacy of tacrine in the treatment of AD as demonstrated in a study of similar design conducted in the US and studies using different designs., (1995 Lippincott Williams & Wilkins.)