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1.
Neuropsychologia ; 50(8): 1871-81, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22525705

ABSTRACT

Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a 12-week computer-based memory-attention training program based on recognition in subjects with A-MCI and compared their performances with those of A-MCI controls trained in cognitively stimulating activities. The effect of training was assessed by comparing outcome measures in pre- and post-tests 15 days before and after training. To evaluate the duration of training benefits, a follow-up test session was performed 6 months after memory and attention training or cognitively stimulating activities. Outcome measures showed that the trained group, compared to control group, improved episodic recall and recognition. Six months after training, scores remained at the level of the post-test. Since the training program was exclusively based on recognition, our results showed a generalization from recognition to recall processes, which are memory components that represent part of the core cognitive impairments in individuals at risk of converting to AD. Thus, cognitive training based on recognition holds promise as a preventive therapeutic method and could be proposed as a non-pharmacological early-intervention strategy. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action.


Subject(s)
Cognitive Dysfunction/rehabilitation , Computer-Assisted Instruction/methods , Memory , Mental Recall , Neuronal Plasticity , Recognition, Psychology , Aged , Alzheimer Disease/prevention & control , Attention , Case-Control Studies , Female , Humans , Male , Neuropsychological Tests
2.
Encephale ; 36(4): 314-25, 2010 Sep.
Article in French | MEDLINE | ID: mdl-20850603

ABSTRACT

INTRODUCTION: The early diagnosis of Alzheimer's disease is a new challenge. This study concerns 50 patients, 34 females (68 %) and 16 males (32 %) with Alzheimer (AD), according to NINCDS-ADRDA diagnostic criteria. OBJECTIVES: To systematically evaluate in all patients behavioral and psychological signs and symptoms of dementia (BPSSD), according to the stage of AD, with the patients of our population separated into two MMS groups. METHODS: The first group was composed of patients with an MMS score from 10 to 20 (eight males and 19 females). Patients of the second group had an MMS score between 21 and 28 (eight males and 19 females). The Neuro-Psychiatric Inventory (NPI) was used to collect information on the presence of BPSSD in AD patients. NPI scores were correlated to the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog) that permits evaluation of the severity of cognitive impairment in AD patients. Before starting the study, all patients gave their informed consent to participate in the study of BPSSD in AD. Statistical treatment of data was performed using STATVIEW. RESULTS: Our study demonstrates that BPSSD are present not only in early but also in moderate stages of AD. As cognitive impairment, BPSSD are an integrate part of the clinical picture. With a frequency of 74 % for the whole population, "anxiety" represented the more predominant BPSSD for all our patients at all stages of AD. At the very early stages of AD, BPSSD appeared to precede cognitive disorders. CONCLUSION: The symptomatic association of "depression", "agitation", and "irritability of mood" may remain in a steady state for a few months before the appearance of verbal episodic memory impairment, which is characteristic of hippocampus involvement. "Irritability" seems to specifically characterise the initial phase of AD. On the other hand, two BPSSD are characteristic of the late stages of AD: "sleep disorder" and "hallucinations".


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Mental Disorders/diagnosis , Mental Disorders/psychology , Aged , Aged, 80 and over , Alzheimer Disease/classification , Alzheimer Disease/pathology , Cognition Disorders/classification , Cognition Disorders/diagnosis , Cognition Disorders/pathology , Cognition Disorders/psychology , Delusions/classification , Delusions/diagnosis , Delusions/pathology , Delusions/psychology , Depressive Disorder/classification , Depressive Disorder/diagnosis , Depressive Disorder/pathology , Depressive Disorder/psychology , Disease Progression , Female , Frontal Lobe/pathology , Hallucinations/classification , Hallucinations/diagnosis , Hallucinations/pathology , Hallucinations/psychology , Hippocampus/pathology , Humans , Irritable Mood , Magnetic Resonance Imaging , Male , Mental Disorders/classification , Mental Disorders/pathology , Mental Status Schedule , Middle Aged , Neocortex/pathology , Neuropsychological Tests/statistics & numerical data , Psychometrics , Psychomotor Agitation/classification , Psychomotor Agitation/diagnosis , Psychomotor Agitation/pathology , Psychomotor Agitation/psychology , Sleep Wake Disorders/classification , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/pathology , Sleep Wake Disorders/psychology
3.
Neurology ; 72(19): 1669-76, 2009 May 12.
Article in English | MEDLINE | ID: mdl-19433740

ABSTRACT

BACKGROUND: Frontotemporal dementia associated with motor neuron disease (FTD-MND) is a rare neurodegenerative disorder that may be inherited by autosomal dominant trait. No major gene has been identified but a locus was mapped on chromosome 9 (9p21.3-p13.3). METHODS: Ten French families with FTD-MND were tested for linkage to the 9p21.3-p13.3 region. We report extensive mutation screening in 9p-linked families and their clinical characteristics. RESULTS: We identified six new families with evidence for linkage to the chromosome 9p. Cumulative multipoint LOD score values were positive between markers D9S1121 and D9S301, reaching a peak of 8.0 at marker D9S248. Haplotype reconstruction defined the telomeric boundary at marker AFM218xg11, slightly narrowing the candidate interval. We found no disease-causing mutations by sequencing 29 candidate genes including IFT74 and no copy number variations in the 9p region. The mean age at onset was 57.9 +/- 10.3 years (range, 41-84), with wide heterogeneity within and among families suggesting age-dependant penetrance. The patients presented isolated FTD (32%), isolated MND (29%), or both disorders (39%). The general characteristics of the disease did not differ, except for an older age at onset and shorter disease duration in the 9p-linked compared to nonlinked families. TDP-43-positive neuronal cytoplasmic inclusions were found in cortex and spinal cord in 3 patients. CONCLUSIONS: This study increases the number of 9p-linked families now reported and shows that this locus may have a major effect on frontotemporal dementia (FTD) and motor neuron disease (MND). Considering our results, the causative gene might be implicated in at least 60% of the families with FTD-MND disorder.


Subject(s)
Chromosomes, Human, Pair 9/genetics , Dementia/genetics , Genetic Linkage/genetics , Genetic Predisposition to Disease/genetics , Motor Neuron Disease/genetics , Mutation/genetics , Adult , Age of Onset , Aged , Aged, 80 and over , Chromosome Mapping , DNA Mutational Analysis , Dementia/complications , Female , Genetic Markers/genetics , Genetic Testing , Genotype , Humans , Male , Middle Aged , Motor Neuron Disease/complications , Pedigree , Penetrance , Young Adult
5.
Encephale ; 33(2): 211-5, 2007.
Article in French | MEDLINE | ID: mdl-17675917

ABSTRACT

The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.


Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use , Indans/pharmacology , Indans/therapeutic use , Piperidines/pharmacology , Piperidines/therapeutic use , Thiamine/analogs & derivatives , Aged , Aged, 80 and over , Attention/drug effects , Donepezil , Drug Therapy, Combination , Female , Hippocampus/drug effects , Humans , Male , Middle Aged , Prefrontal Cortex/drug effects , Severity of Illness Index , Thiamine/pharmacology , Thiamine/therapeutic use
6.
Neuropsychologia ; 45(8): 1948-60, 2007 Apr 09.
Article in English | MEDLINE | ID: mdl-17275041

ABSTRACT

It has been proposed that visual recognition memory and certain attentional mechanisms are impaired early in Alzheimer disease (AD). Little is known about visuospatial recognition memory in AD. The crucial role of the hippocampus on spatial memory and its damage in AD suggest that visuospatial recognition memory may also be impaired early. The aim of the present study was to evaluate which modality, i.e. visual or visuospatial, is more implicated in the early memory impairment in AD. First, to determine onset of memory impairment, we compared the performances of patients with AD to those with amnestic mild cognitive impairment (MCI). Second, to determine the relative contribution of attentional impairment on the performance of MCI and AD patients, we tested the influence of a distractor in the interval between the memory image and recognition tests. Results showed that visuospatial short-term deficits appear earlier than visual short-term ones. In addition to mnemonic deficits, results showed attentional deficiency in both MCI and AD patients. Deficits of performances in visual modality seemed of attentional origin whereas those of visuospatial modality seemed of memory origin. The combination of attentional and mnemonic evaluation is likely to be a promising approach to finding predictive markers that distinguish MCI patients that convert to AD.


Subject(s)
Alzheimer Disease/physiopathology , Attention/physiology , Cognition Disorders/physiopathology , Memory, Short-Term/physiology , Space Perception/physiology , Aged , Aged, 80 and over , Analysis of Variance , Case-Control Studies , Female , Humans , Male , Neuropsychological Tests , Pattern Recognition, Visual , Photic Stimulation/methods , Predictive Value of Tests , Reaction Time
8.
Neurology ; 61(1): 46-54, 2003 Jul 08.
Article in English | MEDLINE | ID: mdl-12847155

ABSTRACT

BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.


Subject(s)
Alzheimer Disease/immunology , Alzheimer Vaccines/adverse effects , Amyloid beta-Peptides/adverse effects , Meningoencephalitis/immunology , Peptide Fragments/adverse effects , Adrenal Cortex Hormones/administration & dosage , Aged , Aged, 80 and over , Alzheimer Disease/complications , Alzheimer Disease/therapy , Alzheimer Vaccines/administration & dosage , Alzheimer Vaccines/immunology , Amyloid beta-Peptides/administration & dosage , Amyloid beta-Peptides/immunology , Antibodies/blood , Brain/pathology , Brain/physiopathology , Disease Progression , Europe , Female , Humans , Magnetic Resonance Imaging , Male , Meningoencephalitis/diagnosis , Meningoencephalitis/drug therapy , Meningoencephalitis/etiology , Middle Aged , Neuropsychological Tests , Peptide Fragments/immunology , Pilot Projects , Plasmapheresis , Safety , Treatment Outcome
9.
J Neuroradiol ; 30(1): 37-45, 2003 Jan.
Article in French | MEDLINE | ID: mdl-12624590

ABSTRACT

DFT (fronto-temporal dementia) was diagnosed in 33 patients (17 males and 16 females), mean age 74.9 years, using the criteria from Neary et al. (1998). The severity of the disease was evaluated based on the presence or absence of 4 clinical groups of signs (behavioral, affective, neurological signs and language) allowing the calculation of a global clinical ratio on 20. A CT-scan and a Single Photon Emission Computed Tomography (SPECT) scan using Tc99m-ECD with quantification of brain perfusion were then performed. This study confirmed the classical clinical forms of DFT: a psycho-affective form (21%), where negative symptoms are predominant, and a behavioral disinhibited form (9%). Most of our cases (40%) corresponded to a global form. Finally we also identified a fourth clinical form: cognitive form because of predominance of language disturbances (30%). Concerning SPECT, we found 4 topographic forms: frontal global (46%), frontal superior (24%), frontal inferior (15%) and frontal unilateral (12%). In the frontal inferior form, behavioral disturbances were correlated to the intensity of frontal inferior hypoperfusion, corresponding to an orbito-frontal dysfunction. In the frontal superior form, psycho-affective disturbances (apathy) were correlated with frontal superior hypoperfusion (anterior cingulum and superior dorso-lateral cortex). Finally, in global and frontal inferior SPECT forms, language disturbances were correlated with a frontal inferior hypoperfusion (prefrontal and inferior left frontal cortex).


Subject(s)
Dementia/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Aged , Dementia/pathology , Female , Humans , Male
10.
Therapie ; 56(1): 29-34, 2001.
Article in French | MEDLINE | ID: mdl-11322014

ABSTRACT

Ursodeoxycholic acid is a protective agent against liver toxicity caused by some drugs. In the present pilot study, we assessed the effect of this bile acid on tacrine-induced hepatotoxicity. Fourteen patients with a diagnosis of Alzheimer's disease received tacrine and ursodeoxycholic acid (13 mg/kg/day) for 105 days. Serum ALAT was the main evaluation criterion. Serum levels of ALAT were compared with those of 100 patients who had been treated with tacrine in the same centre. In patients receiving ursodeoxycholic acid, ALAT serum levels were normal in 93 per cent of cases vs. 69 per cent in control patients and moderate hepatotoxicity (ULN < ALAT < 3 ULN) did not occur while it was present in 25 per cent of controls (p = 0.036). In contrast, the percentage of patients with ALAT > 3 ULN was similar in the two groups (7 per cent vs. 6 per cent). These present findings suggest that UDC could prevent moderate tacrine-induced hepatotoxicity. These results should be confirmed in a controlled therapeutical trial.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Nootropic Agents/adverse effects , Tacrine/adverse effects , Ursodeoxycholic Acid/therapeutic use , Aged , Aged, 80 and over , Alzheimer Disease/complications , Alzheimer Disease/drug therapy , Female , Humans , Liver Function Tests , Male , Nootropic Agents/therapeutic use , Tacrine/therapeutic use
11.
Rev Neurol (Paris) ; 157(11 Pt 1): 1365-75, 2001 Nov.
Article in French | MEDLINE | ID: mdl-11924005

ABSTRACT

We describe the follow-up of a cohort of 255 Alzheimer's disease (AD) patients (81 males, 174 females) treated by tacrine during 4 years. We performed the survey of hepatic, cholinergic and general tolérance. Drug efficacy was measured by MMS examination on weeks 0, 18, 30, 52, 104, 156 and 208. A total of 190 patients (74.5 percent) were dropped out of this study, 75 (29 percent) for adverse events. We found 85 hepatic (33 percent), 79 cholinergic (31 percent), 31 (12 percent) neuropsychiatric and 72 general (28 percent) side effects. In term of drug efficacy we observed a global decline of 2.5 MMS points during the first year and 2 MMS points between W52 and W156. Tacrine's symptomatic efficacy, defined as the number of patients improved or stabilized at W30, was present in 50 patients (46 percent) among the 109 patients reaching W30. The intensity of symptomatic efficacy was expressed by a 2.7 MMS points increase in 37 patients improved on W30. The long term effects of Tacrine, measured by the MMS score at one year, showed a positive impact as the MMS was 2.5 points above the expected score in non treated AD patients. This study raises the practical problem of optimal cholinesterase inhibitors use in AD and the theoretical question of long term action of cholinesterase inhibitors on cerebral lesions of AD.


Subject(s)
Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/therapeutic use , Tacrine/therapeutic use , Aged , Cholinesterase Inhibitors/adverse effects , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Patient Dropouts/statistics & numerical data , Tacrine/adverse effects , Time Factors
12.
Therapie ; 53(1): 67-76, 1998.
Article in French | MEDLINE | ID: mdl-9773102

ABSTRACT

We report our first 100 cases of Alzheimer's (AD) patients treated with tacrine (Cognex) for a period of one year. At the beginning of treatment the mean Mini-Mental-Status (MMS) score was 15.1. To date 71 patients are still under treatment (12 for more than 12 months). Forty-three instances of side-effects were observed, of which 31 involved hepatic side-effects with an increase in ALAT > IN (normal value) (6 cases > 3N), the mean date of appearance was 10.4 +/- 6.8 weeks, there were 16 cholinergic side-effects (nausea, vomiting, diarrhoea), plus 4 neurologic and 2 cutaneous side-effects. These side-effects led to the arrest of the treatment in 19 cases (16 for hepatic toxicity). Treatment was reattempted after interruption in 13 cases; successfully in 3 instances only. The measure of tacrine efficacy was based on 52 MMS score re-evaluations in week 18: there was an increase of the MMS score in 22 cases (3.3 points +/- 2.5), a stabilisation in 11 cases and a decrease in 19 cases (3.3 points +/- 2.2.). In week 30, the MMS scores (35 patients) increased in 9 cases (3.6 points +/- 2.4), stabilized in 5 cases and decreased in 21 cases (3.9 points +/- 3.3). At week 52, only 28 per cent of the patients were considered as either improved or stabilized. We conclude that there is a necessity for close follow-up of tacrine-treated patients, and that globally at 8 months there is an improvement or a stabilization in 40 per cent of patients and long term (at one year) a stabilizing effect on AD patients.


Subject(s)
Alzheimer Disease/drug therapy , Nootropic Agents/therapeutic use , Tacrine/therapeutic use , Aged , Aged, 80 and over , Alanine Transaminase/blood , Alzheimer Disease/psychology , Female , Follow-Up Studies , Humans , Liver/drug effects , Liver/pathology , Male , Mental Status Schedule , Middle Aged , Nootropic Agents/adverse effects , Tacrine/adverse effects , Time Factors , Treatment Outcome
13.
Therapie ; 52(5): 481-2, 1997.
Article in French | MEDLINE | ID: mdl-9501581

ABSTRACT

Follow-up of patients in memory units raises problems of structure, team, diseases, evaluation and organization. Structures could be within the hospital, for early diagnosis, or outside hospital for prevention. The medical team is organized around the neurologist, must integrate different medical specialists (neurologist, psychiatrist, geriatrician) and be composed minimally of a clinician and a psychologist. Diseases range from memory complaint to very serious diseases such as Alzheimer's, vascular or post-traumatic dementia. Therapy includes cognitive stimulation and drug clinical trials. Evaluation requires medico-psycho-social analysis of the patient and his/her family. Memory consulting units could be integrated in a caring network organised in a modular fashion or like a geriatric hospital.


Subject(s)
Memory Disorders/therapy , Follow-Up Studies , France , Hospital Units/organization & administration , Humans , Memory Disorders/diagnosis , Memory Disorders/psychology , Patient Care Team
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