GREFON recommendations for assessment of instrumental activities of daily living in memory clinics.

Following a review of the available assessment scales and current practices of evaluation of instrumental activities of daily living (IADL) in French memory centres by GREFON (Groupe de réflexion sur l'évaluation fonctionnelle; Working Group on Functional Assessment), the main aim of this position paper was to provide good clinical practice (GCP) guidelines for the assessment of IADL. Another aim was to highlight the need for innovative tools adapted to the present and future evolution of such activities in real life, including the use of new technologies, the need for earlier detection of IADL impairment during the diagnostic process of mild neurocognitive disorders, and greater sensitivity to IADL changes during follow-up to allow adaptation of clinical management and evaluation of the impact of therapeutic interventions.

DAD-6: A 6-ltem version of the Disability Assessment for Dementia scale which may differentiate Alzheimer's disease and mild cognitive impairment from controls.

BACKGROUND: The need to detect early changes in instrumental activities of daily life led us to modify the Disability Assessment for Dementia Scale (DAD) by focusing on executive components of 6 instrumental items (DAD-6). AIM: To evaluate the relevance of the DAD-6 for detecting early impairment in a nondemented population. METHODS: The DAD-6 was administered to informants of 84 patients: 31 with mild dementia (MD), 53 with mild cognitive impairment (MCI) and 55 healthy controls. RESULTS: DAD-6 scores gradually decreased with increasing severity of the cognitive status [18 in healthy controls vs. 15.1 ± 3.2 in MCI versus 9.6 ± 3.5 in MD, p < 0.0001). Receiver-operating characteristic curve analyses yielded an optimal cut score of 14 to distinguish MCI from MD with a sensitivity of 0.83 (95% confidence interval 0.74-0.92) and a specificity of 0.84 (0.71-0.94), and a cut score of 15 to distinguish single-domain MCI from multi-domain MCI with a sensitivity of 0.96 (0.90-0.99) and a specificity of 0.54 (0.33-0.75). CONCLUSION: The DAD-6 reliably detects early loss of autonomy due to cognitive impairment.

Relevance of 10-min delayed recall in dementia screening.

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.

[A global intervention program for institutionalized demented patients]. / Méthode de prise en charge globale non médicamenteuse des patients déments institutionnalisés.

INTRODUCTION: Over the last decades many approaches have been developed to manage cognitive and behavioral disturbances in dementia. The present work describes a global intervention program carried out with moderately to severely demented institutionalized patients. The aims of the intervention program are to stimulate and maintain the preserved abilities of demented patients in a supportive context, to decrease the behavioral disturbance and to avoid burnout of care-unit staff. METHODS: This intervention combines different means: psychosocial care (validation therapy, social interaction), cognitive stimulation (memory and verbal training), and motor and sensitive stimulation. The global intervention program requires a special trained team composed of a supervisor, six aid-nurses, an occupational therapist, a speech therapist, a psychomotor therapist and a psychologist. The team cared for the patients five days per week over a three-month period. Assessments were conducted before and after the intervention program to measure the benefit. RESULTS: Positive effects were shown for cognitive abilities, nutritional problems and staff burnout. However, due to the small sample size for this study, more research is needed to verify the effectiveness of this global intervention program, particularly the implications for nutrition. CONCLUSION: This global intervention combined with pharmacological treatment seems to be useful for managing psychological and behavioral disorders of institutionalized demented patients.

[Critical review of psychometric tests]. / Revue critique des tests psychométriques.

In this paper, a critical review of psychometric tests is proposed. The first part describes several aspects of modern, theoretical psychometry and the influence of cognitive psychology. The second part focuses on application of tests to dementia and preliminary results of a longitudinal study of cognitive evolution of patients with mild dementia. Based on this longitudinal study, the batteries of tests to be used for diagnosis, or experimental research, or clinical trials are described. The authors underline the fact that tests are not "good" or "bad" in themselves, and suggest a number of rules for selecting inclusion, evaluation and improvement criteria, related to drug treatment.

Cognitive intervention programmes on patients affected by Mild Cognitive Impairment: a promising intervention tool for MCI?

PURPOSE: This paper examines and reviews studies on the efficacy of computer-based cognitive intervention programmes in the elderly affected by Mild Cognitive Impairment (MCI). MCI patients are at higher risk to progress to dementia. Recent effort has been made to slow the cognitive decline and delay the onset of dementia in this population. METHOD: MEDLINE sources were searched with the following subject headings: computer-based cognitive intervention, cognitive stimulation, cognitive training, aging, elderly, cognitive impairment. Selected studies were quality assessed and data extracted by two reviewers. RESULTS: Several studies reported encouraging results on cognitive interventions programmes as a means to improve cognitive abilities and emotional states and to decrease subjective memory complaints in MCI patients. CONCLUSION: Though both traditional and computer-based cognitive intervention programmes seem to be effective, the computer-based ones present more advantages: 1) they could individualize the programme tailored to the patient's neuropsychological pattern and needs. 2) they permit the user to make an immediate objective comparison with data collected earlier and thus help in setting up a systematic training plan by providing instant value-free feedback. 3) they offer a possibility of a widescale dissemination.

Amnestic syndrome of the medial temporal type identifies prodromal AD: a longitudinal study.

OBJECTIVE: To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). BACKGROUND: Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. METHODS: A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. RESULTS: A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). CONCLUSIONS: The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters.

Accidental MCI in healthy subjects: a prospective longitudinal study.

A study was realized on 130 healthy and autonomous volunteers (60-80 years old) who met specific medical and functional inclusion criteria. A comprehensive battery of neuropsychological tests was performed at baseline (M0), 6 and 12 months (M6, M12). At M0 the results indicated that 65% were cognitively normal on each of all the neuropsychological tests, whereas 35% presented a cognitive deficit on one or more tests. At M12, 52% of the subjects who had a cognitive deficit at M0 remained impaired, whereas 48% normalized their scores: they performed as well as the subjects classified normal at M0. The results also indicated that the subjects who remained impaired at M12, had at M0 low scores on three tests or more, whereas the ones who normalized their scores had one or two failed tests. This study focuses on the risk of false positive cases and shows that low scores can be accidental. The authors propose decision rules allowing to reduce the risk of false positive cases. The observation of accidental impairment invites to be cautious and makes this 1-year follow-up study particularly relevant, since a 1-year follow-up is generally needed to diagnose very mild dementia.

Psychometric tests in ageing.

In order to detect and analyze early cognitive disorders related to ageing, we selected a battery of psychometric techniques. This battery includes a generally accepted test (the PRM of A. Rey) and new computerized tests (reaction-time test and video objects test) designed by ourselves. We used this battery with aged adults ('normal' and 'impaired' outpatients) and young adults ('normal'). Preliminary results indicate an early decline of spatial structuralization and intellectual associative mechanisms necessary to the efficiency of memory, and also confirm the slowing down in the visual-auditory-motor coordination. The data show how new computerized techniques can be helpful tools to quantify early cognitive disorders.

The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer's disease.

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.

Apolipoprotein E phenotypes in demented and cognitively impaired patients with and without cerebrovascular disease.

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).

A double-blind, placebo-controlled, enriched population study of tacrine in patients with Alzheimer's disease.

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.