F. Latour

Executive functions deficit in mild cognitive impairment.

ObjectiveTo investigate whether patients diagnosed with amnestic mild cognitive impairment (MCI) have also impairment in attention/executive functions, and therefore to clarify whether all subcomponents of executive control are equally affected in MCI. BackgroundMCI refers to the transitional state between normal aging and dementia. Amnestic MCI is characterized by impaired episodic memory, although subtle impairment of executive functions has been noted on neuropsychologic tests. MethodsWe investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. ResultsMCI patients had significantly lower scores on all measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on Modified Card Sorting Test and the lowest performance on the Stroop Test (P<0.02). ConclusionsOur findings showed impairment in episodic memory performance in MCI as compared with that of controls. In addition, MCI patients had problems with response inhibition, switching, and cognitive flexibility, which encompass various aspects of executive functions. This suggests that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone.

Patterns of memory impairment and perseverative behavior discriminate early Alzheimer's disease from subcortical vascular dementia

Previous research suggests that the neuropsychological deficits in Alzheimers disease (AD) are different from that of vascular dementia (VaD), especially with respect to memory, language and executive functions, but negative findings were reported. Our objective was to clarify the cognitive syndrome in AD and VaD in the early stage of these disorders. We investigated 45 patients with early AD, 23 patients with subcortical VaD and 35 normal controls. All subjects were assessed with neuropsychological battery designed to measure memory, language, praxis and executive functions. Patients with AD had significantly worse scores on Story Recall (p<0.02) and on all measures of the Free and Cued Selective Reminding Test (p<0.03 to 0.001) than did patients with VaD, as well as greater number of perseverations (p<0.02) on category fluency. Conversely, VaD patients had more perseverations (p<0.02) on the Modified Card Sorting Test. Despite the similar degree of overall cognitive deterioration, the findings show more impaired retrieval from long-term storage in AD than in VaD. Moreover, the data suggest that AD and subcortical VaD affect perseverative behavior in a different fashion. These results may be helpful in differentiating AD from VaD in the early stage of these disorders, when mental impairments are not pervasive yet.

Patients With Alzheimer's Disease Living at Home in France: Costs and Consequences of the Disease

Alzheimers disease (AD) creates a substantial burden on human and financial resources. However, there are few data relating to the cost of AD in France. This retrospective study assesses the total costs of caring for home-based patients with mild to moderate AD. Pattern of care, sociodemographic data, caregiver burden, and estimated net costs of caring for AD patients were assessed in a stratified sample of 50 untreated AD patients. The net costs of caring for all AD patients who completed all study parameters increased with decreasing cognitive ability. Unpaid assistance was the most costly component of the total cost of care. Mini-Mental State Examination scores correlated strongly with functional status, and instrumental activities of daily living scores were a robust indicator of the magnitude of behavioral, cognitive, and dependence problems. This study suggested a significant link between costs of caring for an AD patient at home and disease severity. (J Geriatr Psychiatry Neurol 2003; 16:140-145)

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 ε4 allele carriers (ε4+) and 43 non‐ε4 carriers (ε4–). 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 ε4– and ε4+ groups. The cut‐off point for being considered as responsive to tacrine treatment was a 4‐point decrease in the ADAS‐Cog score.

Association of the Apolipoprotein E ε4 Allele with Late-Onset Depression

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer’s disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE Ε4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE Ε4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE Ε4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0–14.0) or LOD (OR = 6.1, 95% CI, 1.9–19.0) than of EOD (OR = 0.7, 95% CI, 0.2–2.5). These results suggest an association between the ApoE Ε4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an Ε4-dependent pathway.

Detection of cerebral aging, an absolute need: predictive value of cognitive status

Cognitive performance is predictive of functional status, morbidity and mortality in the elderly. In the SYST-EUR study, the Vascular Dementia Project run on 3,111 subjects 60 years old and over, with isolated systolic hypertension, has shown that the cognitive status as measured by the MMSE was inversely correlated with systolic blood pressure (p < 0.001) and age (p < 0.001) and positively correlated with the level of education (p < 0.001). It is significantly lower in patients with cardiovascular complications (p = 0.0001). Moderate alcohol consumption is linked to a higher MMSE score in women (p < 0.001) but not in men. In this study, the incidence of dementia is low and significantly related to the baseline value of the MMSE score and further analysis will show the influence of the treatment of systolic hypertension with calcium antagonists as first step on this incidence.

The Apolipoprotein E ε4 Allele

The overlap between symptoms of depression and dementia in elderly patients has been well established. Depressed elderly patients often complain of poor memory. They may develop cognitive dysfunction which in some cases may be severe enough to meet the criteria for dementia. Some authors have suggested that depression in the elderly increases the risk of dementia. Alternatively, depression may be an early manifestation of dementia (Davanand et al., 1996).

E - 9 Les anticholinestérasiques dans la MA : efficacité à long terme sur les fonctions cognitives et impact des inhibiteurs calciques

Introduction L’efficacite a long terme des anticholinesterasiques dans la maladie d’Alzheimer (MA) est mal connue et l’impact des traitements antihypertenseurs sur le declin cognitif dans la MA est insuffisamment documente. Objectifs Determiner l’efficacite du traitement anticholinesterasique sur les fonctions cognitives a long terme chez des patients atteints de MA et apprecier l’influence des traitements antihypertenseurs sur la reponse au traitement. Methodes Une etude retrospective a ete menee chez 179 patients presentant une MA, traites par anticholinesterasiques pendant au moins trois ans. L’evaluation des fonctions cognitives a ete realisee tous les ans par le Mini Mental State Examination (MMSE). L’influence sur la reponse au traitement de l’âge, du sexe, du degre de severite de la demence, des facteurs de risque vasculaires et de differents traitements antihypertenseurs a ete evaluee grâce a une analyse de variance. Resultats La cohorte (âge moyen = 79 ans, MMSE moyen d’entree = 21,9 +/- 4,7) a ete suivie en moyenne 4 ans (range : 3-6,1). A 3 ans, 25 % des patients avaient conserve leur MMSE d’entree. Le taux de sujets repondeurs (maintien du MMSE a 3 ans) chez les sujets prenant des antagonistes calciques (ICA) etait de 44,8 % contre 18,7 % chez les non consommateurs de ce traitement (p = 0,0086) apres ajustement sur les facteurs confondants. Discussion Un quart de la population garde un MMSE stable a 3 ans et la baisse moyenne annuelle du MMSE apparait moindre que celle observee dans les cohortes de sujets atteints de MA, non traites, temoignant ainsi de l’efficacite a long terme des anticholinesterasiques. Les ICA apparaissent comme un facteur influencant positivement la reponse au traitement anticholinesterasique. Conclusion Le benefice des anticholinesterasiques se maintient a long terme. Les ICA pourraient ameliorer la reponse aux anticholinesterasiques grâce a un role neuroprotecteur, rendant necessaire la realisation d’etudes prospectives.

Réflexion éthique d’un Centre Mémoire de Ressources et de Recherche autour de la maladie d’Alzheimer et maladies apparentées

Resume Parce qu’elle atteint les fonctions superieures, la demence est une maladie particuliere et le patient dement est un malade singulier qui souleve de nombreuses et difficiles questions, tout particulierement en terme d’ethique.En effet, la dimension cognitive de la maladie nous place face a un patient vulnerable, qui ne sera plus a meme de choisir et de decider pour lui-meme, mais qui reste une personne qui, en tant que telle, doit etre ecoutee, entendue, informee, accompagnee et respectee dans sa dignite. La reflexion ethique vise a promouvoir des modalites de prise en charge adaptees a la dimension deficitaire de la maladie afin de preserver, a tous les stades de la maladie, la dignite, le respect et la protection de la personne. La commission ethique du Centre Memoire de Ressources et de Recherche d’Ile-de-France inscrit cette reflexion dans sa demarche pour definir les facteurs ethiques a prendre en consideration dans nos actions et nos pratiques.

Tratamiento de la demencia

Durante estos ultimos anos, se han realizado ensayos terapeuticos para el tratamiento de la enfermedad de Alzheimer (EA) y de las demencias vasculares. En concreto, el tratamiento sintomatico de la enfermedad de Alzheimer ha experimentado considerables progresos con la comercializacion de los anticolinesterasicos. En el campo de la prevencion, el beneficio de los inhibidores del calcio, de los tratamientos antirradicales, antiinflamatorios e inmunitarios, todavia esta en estudio. Las sustancias que actuan sobre la via beta-amiloide (por ejemplo, inhibidores de las beta y de las gamma-secretasas), los factores de crecimiento neuronal, las terapias genicas y los trasplantes neuronales son otras vias con un futuro prometedor. Por otra parte, se ha subrayado recientemente la relacion entre la enfermedad de Alzheimer y la demencia vascular. Los datos epidemiologicos han demostrado una correlacion entre la presencia de factores de riesgo vascular (hipertension arterial, diabetes, hipercolesterolemia o arritmia completa por fibrilacion auricular) y la posterior aparicion de declive cognitivo, e incluso de demencias, tanto vasculares como degenerativas. La identificacion de estos factores permite plantearse para los proximos anos una posible prevencion de las demencias mediante un tratamiento adecuado que comprenda tratamientos antihipertensores, hipocolesterolemiantes, antidiabeticos o antiagregantes plaquetarios. Los datos recientes de los grandes ensayos terapeuticos convergen en senalar el papel preventivo del tratamiento antihipertensor en la aparicion de la enfermedad de Alzheimer y de las demencias vasculares.