Characteristics of Alzheimer's Disease Patients with Severe Executive Disorders.

BACKGROUND: Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations. OBJECTIVE: The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction. METHODS: The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery. RESULTS: 381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as ≥2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months. CONCLUSIONS: Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes.

Cross-validation of a Shortened Battery for the Assessment of Dysexecutive Disorders in Alzheimer Disease.

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

Validation of the Test Your Memory (F-TYM Test) in a French memory clinic population.

The Test Your Memory (TYM) test has been proposed for screening dementia. We present a French version and its validation in memory clinics. F-TYM was administered to 201 patients with memory complaints visiting five secondary referral hospital centers. Final diagnosis was dementia in 34%, amnestic mild cognitive impairment (MCI) in 32%, non-amnestic MCI in 11%, absence of cognitive disorder in 23% and F-TYM scores were respectively (M ± SD) 30.9 ± 7.6, 40.5 ± 6.3, 44.3 ± 4.5 and 43.5 ± 6.6 (p < .0001). F-TYM showed high correlation with MMSE (r = .78), excellent internal consistency, no effect of educational level, sex, or mood but a significant effect of age (p = .004). A F-TYM score ≤ 39 had 0.90 sensitivity and 0.70 specificity for diagnosis of dementia. F-TYM was unable to discriminate MCI and patients without cognitive disorders. F-TYM could be proposed for screening of dementia in patients with memory complaints.

Parkinson's disease dementia can be easily detected in routine clinical practice.

Parkinson's disease (PD) is mainly characterized by its motor manifestations, but it is also frequently associated with dementia. Early diagnosis of PD dementia (PDD) is particularly important because effective cholinesterase inhibitor treatments are available. This study aimed at validating a short procedure for screening for PDD in routine clinical practice and which adopts recently published diagnostic criteria. One hundred eighty-eight patients with PD participated in the study. The examination procedure comprised three steps: standard clinical examination, a short cognitive function assessment fulfilling the requirements of the Movement Disorders Society (Mini Mental State Examination, five-word test, word generation task, and impact on daily life, including a questionnaire on compliance with medication) and an extensive evaluation of cognitive functions and behavior. After each step, the suspected presence or absence of dementia was recorded. After the short cognitive function assessment, PDD was suspected in 18.62% of the patients [95% confidence interval (CI): 13.32-24.93%]. After the extensive assessment, 21.81% (95% CI: 16.13-28.40%) met the criteria for probable PDD. The short battery's sensitivity and specificity were 65.85% (95% CI = 49.41-79.92%) and 94.56% (95% CI = 89.56-97.62%), respectively. A stepwise logistic regression analysis showed that use of a specific cut-off considerably enhanced the short battery's sensitivity (85.37%, 95% CI = 70.83-94.43%) without decreasing its specificity (83.67%, 95% CI = 76.69-89.25%). With an easy-to-use, short battery of tests that are commonly used in routine clinical practice, it is possible to diagnose PDD in accordance with reference criteria and with the same sensitivity and specificity as in a more extensive evaluation.

Fast cognitive decline at the time of dementia diagnosis: a major prognostic factor for survival in the community.

BACKGROUND/AIMS: Current findings suggest the existence of a category of fast cognitive decliners with a poorer prognosis but better treatment response. Our study aimed at confirming the concept of fast decliners at the time of Alzheimer's disease (AD) diagnosis which best predicts mortality, in an unselected sample. METHODS: 245 incident cases of AD were selected from the French longitudinal cohort PAQUID. We investigated a different threshold of cognitive decline [measured by the annual loss of points in the Mini Mental State Examination (MMSE) score] to define when a subject could be considered as a fast decliner. We used Cox proportional hazards models to study the relation between cognitive decline and mortality. RESULTS: The significant threshold of decline associated with a higher mortality rate was a loss of 3 points per year in the MMSE score. Among the 245 AD cases, 83 (33.9%) subjects were considered as fast decliners. Of them, 78.3% died during the follow-up compared with 63.0% of the slow decliners (RR = 1.7, 95% CI 1.2-2.5). CONCLUSION: These results constitute an empirical validation of the concept of fast decliners in community-based AD patients and justify the cutoff of 3 points for the definition of this condition.

Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson's disease.

INTRODUCTION: The severe, cortical, cholinergic depletion accompanying Parkinson's disease (PD) is considered as a highly probable correlate of cognitive and behavioural dysfunction. Recent studies have demonstrated that cholinesterase inhibitors (notably rivastigmine) are beneficial in patients suffering from dementia associated with PD (PDD). However, the primary efficacy variables used in such work came from scales designed for Alzheimer's disease (AD), even though the cognitive symptoms in PD and AD dementia do not overlap completely. The aim of the present study (a double-blind, placebo-controlled clinical trial) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N Engl J Med 2004) participated in this study. They suffered from mild to moderately severe dementia (MMSE scores above 10 and below 24), with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD. Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per day) or placebo. The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits. RESULTS: Compared with placebo, a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale (p = 0.031), with a trend towards a significant improvement in the "Attention" subscale score (p = 0.061). Correlation analysis showed that in the rivastigmine group, performance on the Mattis "Attention" and "Initiation" subscales appeared to contribute heavily to the improvement in the overall score. Moreover, the latter was also related to an improvement in activities of daily living and a reduction in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating scale (which comprises items that are sensitive to executive dysfunction), the present study confirmed that rivastigmine has a beneficial effect on cognitive function in PDD. Despite our study's small sample size, the Mattis scale was able to detect this improvement and could thus be considered as an interesting outcome measure in further work.

[Oestro-progestagen treatment combined with rivastigmine in menopausal women suffering from Alzheimer's disease. The results of a 28-weeks controlled study]. / Traitement estroprogestatif en association à la rivastigmine chez des femmes ménopausées atteintes de la maladie d'Alzheimer. Résultats d'un essai contrôlé de 28 semaines.

OBJECTIVE: To compare the efficacy on cognitive function of the combination of hormone replacement therapy with rivastigmine, acetylcholinesterase inhibitor, in menopausal women suffering from mild to moderately severe Alzheimer's disease. METHOD: This was a randomised double blind study of 117 women suffering from mild to moderately severe Alzheimer-like dementia (MMSE between 10 and 26). The patients were randomly assigned to continuous hormone therapy (n=59) and placebo (n=58), all receiving treatment with rivastigmine. Follow-up was of 28 weeks. ASSESSMENT CRITERIA: ADAS-Cog (Alzheimer's disease assessment scale--cognitive subscale) (primary endpoint); MMSE (mini mental state examination), GDS (global deterioration scale), CGC-Plus (clinical global change-plus), NPI (neuropsychiatric inventory), IADL (instrumental activities of daily living). Data regarding tolerance was recorded. RESULTS: No significant difference was observed in the parameters assessing efficacy (cognitive function, global assessment, functioning, neuropsychiatric symptoms) and tolerance between the two groups of treatment. CONCLUSION: Oestro-progestagen treatment did not provide further improvement when combined with rivastigmine during mild to moderately severe Alzheimer's disease.