Alzheimer Disease: Rigaud AS

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM, Anonymous00344. · CHU Casselardit, Toulouse. · Rev Neurol (Paris). · Pubmed #16244574 No free full text.

Abstract: Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

Traykov L, Rigaud AS, Cesaro P, Boller F. · CHU Henri-Mondor, Université Paris XII, 51, avenue du Maréchal de Tassigny, 94010 Créteil. · Encephale. · Pubmed #17675928 No free full text.

Abstract: This analysis is centered on the study of cognitive disorders in Alzheimer's disease (AD), mainly for major neuro-psychological functions. We insist on the heterogeneity of the clinical picture peculiarly in the early stages of the illness, even if the deficits of episodic memory and of attentional/executive capacities are the first to deteriorate, preceding impairment in perceptual and language function and potentially having a substantial impact on the patient's capacity to cope independently. An episodic memory deficit is the hallmark of AD, but it must be stressed that this deficit may take different forms and its origin may be traced back to different cognitive mechanisms. One of the most striking aspects of episodic memory impairment in AD is the rapidity of forgetfulness on which screening and diagnostic tests of AD are based. There is some evidence that the episodic memory deficit in AD is one of learning (encoding and storage) of information rather than to a deficit of retrieval. Furthermore, episodic memory performance in AD depends on the integrity of semantic memory abilities, so giving support to a hierarchical model of organization of human memory. Finally, recent results show that an impairment of conscious recollection is responsible for the poor performance of AD patients in recognition memory. Executive deficits appear predominantly in tasks requiring cognitive flexibility and self-monitoring. With the progression of the disease, additional deficits are observed in the verbal concept formation abilities. These findings might be also very useful in the differential diagnosis between AD and the other cortical and subcortical dementias, as well as in the differentiation between AD and fronto-temporal dementia. We consider that studying early stages of the illness is necessary to delineate the diagnostic signs, to validate the new therapeutic experiments, to predict stages of decline. Recent research suggested that onset of AD is commonly preceded by an interim phase known as mild cognitive impairment (MCI). MCI refers to the clinical condition in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. Persons who experience this condition are at increased risk for the development of AD. In MCI, despite the comparable global cognitive functioning, the findings show more impaired retrieval from long-term storage than in NC. The cued recall improves slightly the total recall but the recognition is significantly impaired. Moreover, the data indicate that MCI patients had additional problems with response inhibition, switching and cognitive flexibility. 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. As preventive strategies are developed and new cognitive enhancing therapies emerge, these results may also help us to define which domains are expected to improve in MCI populations.

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM. · No affiliation provided · J Nutr Health Aging. · Pubmed #16222399 No free full text.

This publication has no abstract.

Antoine V, Rigaud AS. · Consultation de la mémoire, CHI Poissy-Les Maisonnées, rue du Champ-Gaillard, 78300 Poissy, France. · Rev Med Interne. · Pubmed #15951064 No free full text.

Abstract: BACKGROUND: Dementia is nowadays of major importance in public health. Alzheimer's disease and vascular cognitive impairments are its main aetiology in the elderly. The cause of Alzheimer's disease remains unknown. The factor initiating the physiopathology of this neurodegenerative disease is source of controversy. CURRENT KNOWLEDGE AND KEY POINTS: The theory of a neurotoxicity initiated by amyloid deposition is questioned. A growing number of data suggest a central role of cardiovascular risk factors and alteration of arterial walls, inducing chronic brain hypoperfusion, as the primary trigger in the physiopathology of the disease. These data are based on epidemiological, physiopathological, neuroimaging, neuropathological and pharmacological studies. However, the exact link between arteriosclerosis, vascular cognitive impairment and Alzheimer's disease remains controversial. FUTURE PROSPECTS AND PROJECTS: These debates point out the crucial importance of the assessment of cardiovascular risk factors, as a preventable cause, either of cognitive decline, morbidity and mortality. In this aim, major targets could be different when primary or secondary prevention are at stake. These controversies also suggest new research directions towards Alzheimer's disease physiopathology, and for pharmacological interventions aimed on the prevention of cognitive decline or the curative treatment for this disease.

Baudic S, Traykov L, Rigaud AS, Césaro P. · Inserm/UPVM unité 421, faculté de médecine, 8, rue du Général-Sarrail, 94010 Créteil cedex, France. · Rev Med Interne. · Pubmed #15913849 No free full text.

Abstract: PURPOSE: Neuropsychology provides essential information to all participants (physicians, psychologists, occupational therapists) involved in the treatment of the elderly. When treating depressed elderly patients, a comprehensive neuropsychological examination is required for diagnosis, prognosis and to control the effectiveness of antidepressant treatment. KEY MESSAGE AND RECENT FACTS: Depression in elderly people is frequent and difficult to diagnose. Some forms of depression usher in or are associated with a neurodegenerative disease. In the case of diagnosis, the neuropsychological examination should furnish useful information to guide the clinician. The qualitative analysis of results (strategies used and type of errors) and the weakening of cognitive processes efficiency provides supplementary information and increases the reliability of the diagnosis. It also gives information about the long term evolution of cognitive deficits. It should reveal the presence of characteristics which help to distinguish patients who are developing dementia (predictive power of certain tests). Finally, it enables the clinician to evaluate the outcome of antidepressant treatment, to adjust the prescription according to the performance and to adapt an holistic treatment. PERSPECTIVE AND PROJECTS: A neuropsychological examination may provide new perspectives, such as the possibility of predicting the outcome of dementia which are accompanied by affective disorders, such as Alzheimer's disease, vascular dementia and frontotemporal dementia. Neuropsychology may thus improve the treatment of these patients by providing information to a better understanding of their deficits and their impact on daily living abilities.

Olde Rikkert MG, Rigaud AS. · Dept. Geriatric Medicine, University Hospital Nijmegen, Code 318, PO Box 9101, 6500 HB Nijmegen, The Netherlands. · Z Gerontol Geriatr. · Pubmed #11828891 No free full text.

Abstract: BACKGROUND: Melatonin is a hormone and antioxidant produced by the pineal gland of which four neurobiological roles have been claimed in the aged population: anti-ageing agent; free-radical scavenger; regulator of circadian rhythm; endogeneous sleep-inducer. The "melatonin replacement" hypothesis states that 1) the well-evidenced age-related decline contributes to insomnia and that 2) replacement with physiological doses of melatonin improves sleep. The aim of this review was to determine the evidence for the efficacy of melatonin in elderly insomniacs. METHODS: MEDLINE's database from 1990-2000 was searched with "melatonin", "geriatrics" and "(frail)-elderly" as major sub-headings. This resulted in 78 articles: only studies with empirical treatment data were reviewed (N = 12). RESULTS: Six reports (abstract, research letter, retrospective case study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep quality improved and in patients with Alzheimer's disease sundowning was reduced. In 6 double blind, randomised crossover trials, a total number of 95 patients (mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6 mg; most took a single dose 30-120 min before bedtime. In 3 studies a slow release form was used. Sleep quality was objectively measured by wrist actigraphy (n = 4) and polysomnography (n = 2), and additionally subjective sleep quality was assessed (n = 2). Sleep latency decreased significantly in 4 studies. In 3 studies other measures of sleep quality (sleep efficiency, total sleep time and wake time during sleep) improved. Subjective sleep quality did not improve. No early-morning sleepiness occurred. Comparison of the studies suggests that melatonin is most effective in elderly insomniacs who chronically use benzodiazepines and/or with documented low melatonin levels during sleep. CONCLUSION: There is sufficient evidence that low doses of melatonin improve initial sleep quality in selected elderly insomniacs. However, larger randomized controlled trials, with less strict inclusion criteria are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric patients who suffer from insomnia, before wide-spread use can be advocated.

Lebert F, Robert P, Rigaud AS. · Centre de la Mémoire, Hôpital Roger Salengro, Centre Hospitalier Universitaire, Lille. · Rev Neurol (Paris). · Pubmed #10992121 No free full text.

Abstract: Behavioral disorders are major manifestations of Alzheimer's disease and other forms of dementia. They are associated with caregiver distress, increase the likelihood of institutionalization and may be associated with more rapid cognitive decline. The first step of treatment strategy is an assessment of these disorders. Treatment of behavioral signs is an etiological treatment. Acute behavioral signs are often related to an unknown somatic disease. Chronic signs are often symptoms of the neurological dementia and can be reduced, especially by serotonergic agents and anticonvulsivants. The new antipsychotics are a good alternative to classic neuroleptics known for their frequent cognitive side effects in demented patients. Anticholinesterasic drugs can positively influence noncognitive signs. The treatment of behavioral and psychological symptoms of dementia (BPSD) involves a number of specific interventions including cognitive stimulation which has shown effectiveness on both cognitive functions and quality of life. Prevention of BPSD includes safety measures such as evaluation of suicidality and violence, vigilance regarding neglect and abuse, planning for legal issues due to the patient's incapacity. Families or caregivers should be provided with counseling, education and support. The treatment of BPSD is part of a global and multimodal care which involves general practioners, nurses, social workers, physiotherapists, neuropsychologists, speech therapists, memory centers, psychogeriatric and geriatric units, and respite care units, nursing homes and long-term care facilities. The coordination of the professionals is a critical aspect of providing effective care for patients with Alzheimer's disease.

Lôo H, Rigaud AS, Dubois B, Gallarda T, Aurenche S. · No affiliation provided · Encephale. · Pubmed #17115480 No free full text.

This publication has no abstract.

Rigaud AS, André G, Vellas B, Touchon J, Pere JJ, Loria-Kanza Y. · Département de gériatrie, Service du Pr F. Forette, Hôpital Broca, Paris. · Presse Med. · Pubmed #14631268 No free full text.

Abstract: 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.

Rigaud AS, André G, Vellas B, Touchon J, Pere JJ, Anonymous00011. · Department of Geriatrics, Broca Hospital, Paris, France. · Neurology. · Pubmed #12525745 No free full text.

This publication has no abstract.

Traykov L, Rigaud AS, Baudic S, Smagghe A, Boller F, Forette F. · INSERM Unit 324, Paris, France. · J Neurol Sci. · Pubmed #12417380 No free full text.

Abstract: Controversy exists regarding the apolipoprotein E (ApoE) epsilon 4 allele association with vascular dementia (VaD). The results range from increased epsilon 4 frequency, similar to that found for Alzheimer's disease (AD), to no association at all. Our objective was to clarify the relationship between ApoE epsilon 4 allele and cerebrovascular disease (CVD) in demented and cognitively impaired patients. We examined the ApoE phenotypes in a sample of 452 subjects: 219 with AD, 45 with VaD, 62 with mixed dementia (MD), 45 with mild cognitive impairment (MCI) without CVD, 27 in which vascular disease was the most probable cause of cognitive decline (vascular mild cognitive impairment, VMCI) and 54 normal controls (NC). The study of the epsilon 4 allele frequency showed significant differences between: AD group and the VaD, VMCI and NC groups; MCI group compared with VMCI and NC groups; and MD group versus the VaD and NC groups (p<0.05-0.0001). The frequency of the epsilon 4 allele in the VaD and VMCI groups did not differ significantly from NC. In contrast to other studies, we did not detect a relationship between ApoE epsilon 4 allele and clinically diagnosed VaD. Our results also show that the epsilon 4 allele is not associated with cognitive impairment of vascular origin. In addition, we have confirmed that the ApoE epsilon 4 allele occurs frequently in late-onset AD and we have found similar association in cognitively impaired individuals without clinical CVD. These findings should contribute to the assessment of dementia risk profile in the elderly.

Rigaud AS, Traykov L, Latour F, Couderc R, Moulin F, Forette F. · Hôpital Broca, Paris, France. · Pharmacogenetics. · Pubmed #12142731 No free full text.

Abstract: The objective was to evaluate the effects of the apolipoprotein E (ApoE) genotype and gender on the response to donepezil treatment in Alzheimer's disease. ApoE genotyping was performed on 117 patients with mild to moderate Alzheimer's disease who were included in a 36-week open label trial of donepezil therapy. Of these 117 patients, who constituted the intent-to-treat population (ITT), 80 completed the trial, and constituted the evaluable population. Patients were treated blindly in relation to ApoE genotype. Outcome measures were Alzheimer's disease Assessment Scale-Cognitive Component (ADAS-Cog), the Mini Mental State Examination, Instrumental Activities of Daily Living, and the Caregiver-rated Clinical Global Impression of Change. ITT analysis did not reveal significant differences between the responses of epsilon 4- and epsilon 4+ carriers according to the ADAS-Cog (P = 0.28). No differences were found either between the responses of men and women (P = 0.81), and there was no significant interaction between genotype and gender (P = 0.09). Other outcome measures all exhibited similar patterns of change to those seen using the ADAS-Cog. Consequently, these results do not support the hypothesis that the ApoE phenotype and gender are predictors of the response to donepezil in Alzheimer's disease patients.

Rigaud AS, Traykov L, Caputo L, Guelfi MC, Latour F, Couderc R, Moulin F, de Rotrou J, Forette F, Boller F. · Hôpital Broca, 54-56 Rue Pascal, 75013, Paris, France. · Eur J Neurol. · Pubmed #10886308 No free full text.

Abstract: 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.

Traykov L, Rigaud AS, Caputo L, Couderc R, Coste J, Michot JL, de Rotrou J, Amouyel P, Forette F, Boller F. · INSERM Unit 324, 2ter rue d'Alesia, 75014, Paris, France. · Eur J Neurol. · Pubmed #10362893 No free full text.

Abstract: 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).

Visser PJ, Verhey FR, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset PJ, Rigaud AS, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B. · Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. · Neuroepidemiology. · Pubmed #18515975 No free full text.

Abstract: BACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.

Traykov L, Raoux N, Latour F, Gallo L, Hanon O, Baudic S, Bayle C, Wenisch E, Remy P, Rigaud AS. · Hôpital Henri Mondor, Department of Neurology, University Paris XII, Créteil, France. · Cogn Behav Neurol. · Pubmed #18091070 No free full text.

Abstract: OBJECTIVE: To 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. BACKGROUND: MCI 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. METHODS: We investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. RESULTS: MCI 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). CONCLUSIONS: Our 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.

Duron E, Alami A, Pequignot R, Bert P, Rigaud AS, Hanon O. · Service de gériatrie, hôpital Broca, Paris. · Arch Mal Coeur Vaiss. · Pubmed #17928770 No free full text.

Abstract: White matter lesions (WML) are frequently disclosed on elderly people computed tomography (CT) brain scan. OBJECTIVE: To evaluate the relationship between WML and cognitive functions of patients suffering from Mild Cognitive Impairment (MCI). METHODS: We studied the association between WML on CT brain scan and cognitive functions in 136 consecutive elderly subjects attending a geriatric outpatient clinic, suffering from MCI. The global cognitive assessment was based on Mini Mental State Examination (MMSE), a validated comprehensive battery of neuropsychological tests, the Cognitive Efficiency Profile (CEP), a CT brain scan and a complete biological screening. WML on CT brain scan was evaluated by a blinded investigator. RESULTS: In this population, 75 +/- 8 years of age, (women 60%, and hypertension 54%), 33% of subjects had WML on CT brain scan. Patients with WML were significantly older (OR=1.27; IC 95%=1.04 - 1.22), had more frequently a past history of hypertension (OR=2.71; IC 95%=1.06 - 6.96) and more frequently lacunae associated with WML (OR=4.48; IC 95%=1.18 - 16.99). Subjects with WML had significantly poorer cognitive functions than those without WML (CEP score/100=62.33 +/- 13.58 versus 71.87 +/- 14.19, p<0.01 and MMSE score/30=27.02 +/- 2.34 versus 27.97 +/- 1.89, p<0.01) CONCLUSION: Our results showed a relationship between WML on CT brain scan and the depth of cognitive dysfunction among MCI patients. Further long term prospective studies have to be performed to determinate if WML are involved in transitions between MCI and Alzheimer' s disease.

Moulin F, Cantegreil-Kallen I, De Rotrou J, Weinisch E, Batouche F, Richard A, Rigaud AS. · Hôpital Broca, 54-56, rue Pascal, 75013 Paris, France. · Encephale. · Pubmed #17356491 No free full text.

This publication has no abstract.

Traykov L, Bayle AC, Latour F, Lenoir H, Seux ML, Hanon O, Péquignot R, Bert P, Moulin F, Cantegreil I, Wenisch E, Batouche F, Mehrabian S, Rotrou J, Rigaud AS. · Hôpital Broca, Paris, France. · J Neurol Sci. · Pubmed #17337010 No free full text.

Abstract: Late-onset depression (LOD) could be a very early manifestation of Alzheimer's disease (AD), although contradictory results have been reported. Cerebrovascular disease (CVD) may favor the development of LOD, and that the particular forms of vascular depression should be individualized. The Apolipoprotein E (ApoE) epsilon4 allele was shown to be a risk factor for AD. Its role in LOD is controversial, while it is still unknown in vascular depression. Our objective was to clarify the relationship between ApoE epsilon4 allele and LOD in patients with and without CVD. We examined the ApoE phenotypes in a sample of 311 subjects: 50 with vascular LOD, 24 with LOD without CVD, 115 with AD and 122 normal controls (NC). The study of the ApoE epsilon4 allele frequency showed significant differences between: AD group and the vascular LOD and NC groups; LOD group without CVD compared with NC group (p<0.05 to 0.001). The frequency of the epsilon4 allele in the LOD group without CVD did not differ significantly from the AD group, similarly the frequency of the epsilon4 allele in the vascular LOD group was not different from that in NC. The study suggests an association between the ApoE epsilon4 allele and the LOD without CVD. These patients could be at risk of developing AD by an epsilon4-dependent pathway. In contrast, the results show no association between the presence of ApoE epsilon4 allele and vascular depression and provide further evidence in support of the concept that ApoE epsilon4 allele is not associated with clinical CVD.

De Rotrou J, Thévenet S, Richard A, Cantegreil I, Wenisch E, Chausson C, Moulin F, Batouche F, Rigaud AS. · CMRR de l'Hôpital Broca, 54-56 rue Pascal, 75013 Paris, France. · Encephale. · Pubmed #17099590 No free full text.

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Hanon O, Pequignot R, Seux ML, Lenoir H, Bune A, Rigaud AS, Forette F, Girerd X. · Université Paris-Descartes, Department of Geriatrics, Hôpital Broca, Paris, France. · J Hypertens. · Pubmed #16957572 No free full text.

Abstract: OBJECTIVE: To evaluate the relationship between antihypertensive treatments and cognitive function in elderly hypertensive patients with memory complaints. METHODS: The association between cognitive function and antihypertensive drug therapy was studied in 1241 hypertensive elderly patients with memory complaints attending a geriatric outpatient clinic. Cognitive function was assessed using the Mini Mental State Examination (MMSE) and validated neuropsychological tests (Cognitive Efficiency Profile; CEP). Patients were classified into four categories according to their cognitive status: normal cognitive function, mild cognitive impairment (MCI), Alzheimer's disease (AD) or vascular dementia (VaD). RESULTS: In this population aged 78 +/- 8 years, with a mean blood pressure of 152 +/- 19/86 +/- 12 mmHg, antihypertensive treatment was prescribed for 57% of patients. After adjustment for age, sex and education, treated hypertensive patients had better cognitive function than untreated patients (MMSE score 23.9 +/- 5.6/30 versus 22.7 +/- 6.4/30, P < 0.001, CEP score 49.1 +/- 24.9/100 versus 45.4 +/- 23.7/100, P < 0.001). This association was observed independently of the cognitive status, both in normal, MCI, AD and VaD hypertensive patients. The odds ratio (OR) for AD was 0.58 [95% confidence interval (CI) 0.42-0.81] in treated compared with untreated hypertensive patients. In patients on antihypertensive therapy, higher cognitive function was observed in patients using calcium antagonists compared with those without calcium antagonists (CEP 52.9 +/- 24.6/100 versus 46.4 +/- 23.4/100, P < 0.001; OR for AD 0.67; 95% CI 0.45-0.99), independently of blood pressure level. CONCLUSIONS: Antihypertensive therapy was associated with a lower risk of cognitive impairment and AD. In particular, the use of calcium antagonists was associated with a decreased risk of cognitive impairment and AD independently of the blood pressure level, suggesting a specific neuroprotective effect of these antihypertensive agents.

Hanon O, Haulon S, Lenoir H, Seux ML, Rigaud AS, Safar M, Girerd X, Forette F. · Université Paris-Descartes, Department of Geriatrics, Hôpital Broca, Paris, France. · Stroke. · Pubmed #16151027 links to  free full text

Abstract: BACKGROUND AND PURPOSE: To evaluate the relationship between arterial stiffness and cognitive function in a population of elderly subjects reporting memory loss. METHODS: We studied the association between cognitive function and arterial stiffness in 308 consecutive elderly subjects attending a geriatric outpatient clinic reporting memory impairment. Subjects were classified into 4 categories according to neuropsychological evaluation: normal cognitive function, mild cognitive impairment (MCI), Alzheimer disease (AD), or vascular dementia (VaD). Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV) measurement using Complior. RESULTS: In this population, 78+/-8 years of age (women 64%), AD was present in 41%, VaD in 6%, MCI in 27%, and 26% of subjects had normal cognitive function. After adjustment for age, gender, systolic blood pressure, education level, cardiovascular diseases, and antihypertensive therapy, a significant association was observed between PWV and cognitive status (P<0.0001). PWV appears significantly higher in subjects with VaD (15.2+/-3.9 m/s) or AD (13.3+/-2.9 m/s) than in those without cognitive impairment (11.5+/-2.0 m/s; P<0.001). Moreover, PWV was higher in subjects with MCI (12.6+/-2.6 m/s) than in those without cognitive impairment (11.5+/-2.0 m/s; P=0.01). For each 2 m/s increment in PWV, the adjusted odds ratio (95% CI) was 1.73 (1.27 to 2.47) for AD and 3.52 (1.87 to 8.05) for VaD. CONCLUSIONS: Our results showed a relationship between arterial stiffness and cognitive impairment, suggesting that functional changes of the arterial system could be involved in the onset of dementia (VaD or AD types).

Cantegreil-Kallen I, Turbelin C, Olaya E, Blanchon T, Moulin F, Rigaud AS, Flahault A. · Department of Geriatrics, Broca Hospital, Paris, France. · Am J Alzheimers Dis Other Demen. · Pubmed #16136846 No free full text.

Abstract: Most practitioners find disclosing the diagnosis of Alzheimer s disease (AD) to an individual with dementia very difficult. Literature results show a wide variability in attitudes and clinicalpractice, and diagnosis seems to be more often disclosed to caregivers than to patients. The objective of this study was to examine whether and how diagnosis of AD is disclosed in French general practice and which issues are addressed with the patient. A questionnaire was sent via mail to 1,629 general practitioners (GPs), 1,105 belonging to the Sentinel's network and 524 specially recruited doctors practicing in the Rhône-Alpes region. A total of 631 questionnaires were returned (response rate, 39 percent), of which 616 were eligible for analysis. Twenty-eight percent of GPs reported having disclosed diagnosis to the patient (25 percent mentioned "Alzheimer's disease"), whereas 88 percent considered it their role to announce the diagnosis to the patient. Regarding the type of information provided to the patient, only 25 percent discussed the nature of the illness, 23 percent behavioral problems, and 47 percent depression, mainly for psychological reasons (63 percent). Stress was discussed with 79 percent of the caregivers. We concluded that GPs do not discuss the consquences of AD and symptoms (e.g., behavioral disorders) with patients, mainly for psychological reasons, whereas they have a less-reluctant attitude toward caregivers. As the GP has the weighty task of providing ropriate community care and psychological support to the patient, it is of utmost importance to reflect on how disclosure of diagnosis can be facilitated.

Hanon O, Latour F, Seux ML, Lenoir H, Forette F, Rigaud AS, Anonymous00362. · Department of Geriatrics, Hôpital Broca, 75013 Paris, France. · J Nutr Health Aging. · Pubmed #15791354 No free full text.

Abstract: OBJECTIVES: To determine the evolution of blood pressure in patients with moderate Alzheimer's disease among a one year longitudinal survey and to evaluate the relationship between blood pressure and cognitive functions. METHODS: In 327 subjects selected from the French research program on Alzheimer's disease (REAL.FR), systolic and diastolic blood pressure (SBP, DBP) were measured at the time of inclusion (M0), after 6 months (M6) and after 12 months (M12). All subjects were assessed to determine both cognitive functions and capabilities in the activities of daily living using validated cognitive scales [Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale--Cognitive part (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR)], at M0, M6, M12. RESULTS: In this population of patients with moderate Alzheimer's disease, mean age was 78 +/- 7 years and 242 subjects were females (74%). After adjustment for age, gender, body mass index (BMI) and antihypertensive therapy, a significant decrease of blood pressure was observed between M0 and M12, for SBP (139.1 +/- 18 to 136.5 +/- 17 mmHg, p < 0.05) and DBP, (77.6 +/- 12 to 75.8 +/- 10 mmHg , p < 0.05). Demented subjects with the worst cognitive impairment at baseline (tertile1 MMSE, tertile 3 ADAS-Cog, ADL scores between 0 and 4, CDR scores between 10 to 18) showed a larger decrease in SBP and DBP after 12 months. The worst impairment in dementia at baseline was associated with the highest SBP decrease between M0 and M12 (delta SBP tertile 1 MMSE vs tertile 3 MMSE = -5.9 vs + 1.0 mmHg , p < 0.05; Delta SBP tertile 3 ADAS-Cog vs tertile 1 ADAS-Cog = - 5.98 vs + 2.98 mmHg, p < 0.05, Delta SBP ADL 0-4 vs ADL -6 = - 8.7 vs -1.5 mmHg, p < 0.05, delta SBP CDR 10-18 vs CDR 0.5-9.5 = - 6.9 vs -1.7 mmHg, p < 0.05). All these results persisted after adjustment for age, gender and the antihypertensive therapy. Baseline SBP [OR 95% CI = 1.05 (1.02-1.08), BMI [OR 95% CI = 0.88 (0.81-0.95)], ADL score [OR 95% CI = 0.42 (0.22-0.81)] and ADAS-Cog score [OR 95% CI = 1.07 (1.01-1.14)] were significantly associated with the decrease of blood pressure after one year of follow up, independently of age, gender and antihypertensive therapy. In contrast, patients with larger blood pressure decrease (over 10 mmHg reduction of SBP and/or 5 mmHg of DBP) did not demonstrate a more significant worsening of dementia at 12 months in the different scales used. CONCLUSIONS: This study indicates a significant decrease in blood pressure in patients with Alzheimer's disease after one year of follow up, independently of age, gender, BMI and antihypertensive therapy. The largest decrease in blood pressure was observed in patients with the most severe impairment in dementia at baseline, suggesting that blood pressure decrease seems to be mainly a secondary phenomenon in Alzheimer's disorders.

Traykov L, Baudic S, Raoux N, Latour F, Rieu D, Smagghe A, Rigaud AS. · INSERM U.610, Paris, France. · J Neurol Sci. · Pubmed #15760623 No free full text.

Abstract: Previous research suggests that the neuropsychological deficits in Alzheimer's 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.