Alzheimer Disease: Forette F

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.

Forette F, Hauw JJ. · Université Paris V, Hôpital Broca, Fondation nationale de Gérontologie, International Longevity Center (ILC)-France. · Bull Acad Natl Med. · Pubmed #18819689 No free full text.

Abstract: We review the main therapeutic targets in Alzheimer's disease. Current treatments include cholinesterase inhibitors and the glutamate-modulating drug memantin. Other neurotransmitters such as serotonin, histamine and noradrenaline may also be targeted. Although useful, however, these symptomatic treatments do not prevent neuronal degeneration and death. Epidemiological studies suggest that treatments given for other reasons, such as antiinflammatory agents (including NSAIDs), cholesterol-lowering drugs, hormone replacement therapy and antioxidants, may prevent or improve Alzheimer-type dementia, but this is not always borne out in controlled clinical trials. Prevention of hypertension significantly reduces the incidence of vascular dementia and of Alzheimer-type dementia, albeit through an unknown mechanism. Alzheimer's disease is characterized by two main lesions: amyloid plaques and neurofibrillary tangles composed of aggregated A Beta peptides and hyperphosphorylated tau. Active and passive immunization against A beta has given promising results. Other exciting approaches include modulation of A beta processing by inhibiting BACE1 or gamma-secretase or upregulating alpha-secretase; A beta peptide catabolism; inhibition of beta fibrillization; and reducing tau phosphorylation or inhibiting tau aggregation. More remote possibilities include gene therapy and the use of growth factors to increase neurogenesis.

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.

Birkenhäger WH, Forette F, Seux ML, Wang JG, Staessen JA. · Faculty of Medicine, Erasmus University Rotterdam, The Netherlands. · Arch Intern Med. · Pubmed #11176727 links to  free full text

Abstract: The prevalence and incidence of degenerative and vascular dementias increase exponentially with age, from 70 years onward. In view of the increasing longevity of humans, both varieties are bound to evolve into a major problem worldwide. According to several longitudinal studies, hypertension appears to predispose individuals to the development of cognitive impairment and ensuing dementia, after a period varying from a few years to several decades. Antihypertensive drug treatment, according to preliminary evidence, may serve to reduce the rates of such events. Such findings await to be confirmed by formal therapeutic trials against a backdrop of "historical" observational sources.

Petit H, Albarède JL, Bakchine S, Boulliat J, Cogneau J, Darcourt G, Dubois B, Forette F, Franco A, Héres J, Hinault P, Laurent B, Léger JM, Marin La Meslée R, Montagne B, Poncet M, Robert P, Sorbé G, Touchon J, Velas B, Vetel JM. · Neurologue (Clinique Neurologique, CHRU Roger Salengro 59037 Lille Cedex, France. · Rev Neurol (Paris). · Pubmed #10844378 No free full text.

This publication has no abstract.

Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM, Anonymous00149. · Department of Neurology, University of Michigan, 300 N. Ingalls 3D15, Ann Arbor, MI 48109-0489, USA. · Neurology. · Pubmed #15883316 No free full text.

Abstract: BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.

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.

Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, Bossini A, Fagard R, Gil-Extremera B, Laks T, Kobalava Z, Sarti C, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Birkenhäger WH, Anonymous00263. · Department of Geriatrics, Hôpital Broca, CHU Cochin, University of Paris V, 54-56 rue Pascal, 75013 Paris, France. · Arch Intern Med. · Pubmed #12374512 links to  free full text

Abstract: BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

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.

Forette F, Anand R, Gharabawi G. · Centre de Gerontologie, Hopital Broca, 54-56 rue Pascal, 75013, Paris, France. · Eur J Neurol. · Pubmed #10362894 No free full text.

Abstract: Rivastigmine is a carbamate acetylcholinesterase (AChE) inhibitor with central selectivity. Early studies showed that daily doses up to 6 mg/day have some efficacy in patients with dementia of the Alzheimer type (DAT). The present study was designed to assess the safety, tolerability and efficacy of rivastigmine at doses up to 12 mg/day. A total of 114 patients with mild-moderate DAT were randomly assigned to either rivastigmine (b.i.d. (twice daily) or t.i.d. (three times daily)) or placebo in a double-blind fashion titrated to their maximum tolerated dose over 10 weeks followed by an eight-week maintenance phase. The mean maximum tolerated dose was approximately 10 mg/day (b.i.d. or t.i.d.). Gastrointestinal complaints, the majority of which were mild to moderate, were the most frequently reported adverse events. No clinically relevant changes in vital signs, haematology or organ function were detected. Significantly more patients taking rivastigmine b.i.d. were considered improved according to the Clinicians' Interview-Based Impression of Change-Plus (CIBIC-Plus) vs. placebo (57% vs. 16%, respectively; P = 0.027). The Nurses' Observation Scale for Geriatric Patients (NOSGER) (memory component) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) also improved in the rivastigmine b.i.d. group vs. placebo (mean change from baseline on NOSGER = -0.7 vs. +1.3, respectively; P = 0.037: mean change from baseline on ADAS-cog = -2.7 vs. +0.2, respectively; P = 0.054). Despite the relatively small size and limited duration of the study, the finding that rivastigmine induced changes in the same (positive) direction in all three dimensions measured suggests that rivastigmine at doses of up to 12 mg/day has useful efficacy in patients with mild-moderate DAT. Reports from larger phase III studies confirm this finding. The results of this study also suggest that b.i.d. is the more efficacious regimen and has comparable tolerability to the t.i.d. regimen. Copyright Lippincott Williams & Wilkins

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).

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).

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.

Hanon O, Latour F, Seux ML, Lenoir H, Forette F, Rigaud AS. · Service de gériatrie, hôpital Broca, 54-56, rue Pascal, 75013 Paris, France. · Rev Med Interne. · Pubmed #14710447 No free full text.

Abstract: The relationships between arterial hypertension and cognitive decline are complex and studies indicate controversial results. OBJECTIVES: To evaluate, in a cross sectional study, the relationships between cognitive functions and blood pressure in a population of subjects with Alzheimer's disease. METHODS: In 520 subjects of a survey in a French population with Alzheimer's disease, relationships between the severity of cognitive decline and a history of hypertension or blood pressure level have been searched. Cognitive functioning was assessed with validated neuropsychological tests evaluating cognitive functions and the capacities in the activities of daily living (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), Global Deterioration Scale (GDS) of Reisberg). In 456 subjects blood pressure was measured during the consultation. RESULTS: The results indicate that after adjustment on age, sex, education level, and the other cardiovascular risk factors, subjects with a history of hypertension have a more marked cognitive decline than subjects without history of hypertension. Indeed, in subjects with a history of hypertension, the cognitive impairment and its consequences on activities of daily living are more important than in subjects without history of hypertension (ADAS-cog 19.02 +/- 8.48 vs 17.49 +/- 8.53 p = 0.06, MMSE 19.55 +/- 4.41 vs 20.30 +/- 4.42, p = 0.08, score ADL 5.31 +/- 0.86 vs 5.51 +/- 0.87, p = 0.01, CDR 6.94 +/- 3.29 vs 6.19 +/- 3.26 p = 0.03; global CDR 1.18 +/- 0.62 vs 1.05 +/- 0.60, p = 0.03, GDS of Reisberg 4.41 +/- 0.74 vs 4.27 +/- 0.75, p = 0.05). In contrast, no relation between blood pressure measurements and cognitive function is observed, and moreover an inverse correlation between blood pressure and consequences on activities of daily living is found. CONCLUSIONS: This work indicates that relationships between blood pressure and cognitive functions are more complex than a simple linear relation. The present results show that a history of arterial hypertension is associated with a more marked cognitive decline in subjects with Alzheimer's disease. In contrast, when the Alzheimer's disease is already developed no relation between blood pressure and cognitive functions appears and moreover an inverse correlation with the consequences on activities of daily living is found.

Fagnani F, Lafuma A, Pechevis M, Rigaud AS, Traykov L, Seux ML, Forette F. · CEMKA, Bourg-la-Reine, France. · Dement Geriatr Cogn Disord. · Pubmed #14560059 No free full text.

Abstract: In the present study, the socioeconomic impact of the use of the acetylcholinesterase inhibitor donepezil in patients with mild to moderate Alzheimer's disease (AD) living in France was examined. A model was created to extrapolate over a 3-year period the results from placebo-controlled trials together with epidemiological and prevalence data. Costs considered in the model were net societal costs associated with paid and unpaid assistance, general medical consumption and institutional care. The model suggested that delays in cognitive decline and functional dependence due to treatment reduced the time spent in institutional care and the burden on caregivers. Over a 3-year period, total net costs of caring for untreated patients with an initial Mini-Mental State Examination score ranging from 10 to 26 were EUR 53,206 compared with EUR 42,720 for a patient treated with donepezil--an annual cost saving of approximately EUR 3,500 per patient. Cost savings were mainly due to savings in unpaid caregiver time, which, apart from patient institutionalization, represented the most costly component of total care in this study but had no direct budgetary impact. Overall, these data suggest that donepezil is a cost-effective treatment for mild to moderately impaired AD patients living in France.

Rigaud AS, Fagnani F, Bayle C, Latour F, Traykov L, Forette F. · Hôpital Broca, Paris, France. · J Geriatr Psychiatry Neurol. · Pubmed #12967055 No free full text.

Abstract: Alzheimer's 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.

Forette F. · Service de gérontologie, Hôpital Broca, AP-HP Paris. · Presse Med. · Pubmed #12947600 No free full text.

This publication has no abstract.

Rigaud AS, Traykov L, Caputo L, Coste J, Latour F, Couderc R, Moulin F, Boller F, Forette F. · Hôpital Broca, CHU Cochin Port-Royal, Université René-Descartes, Paris V 54/56, rue Pascal, F-75013 Paris, France. · Neuroepidemiology. · Pubmed #11684904 No free full text.

Abstract: 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 epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.

Traykov L, Tavitian B, Jobert A, Boller F, Forette F, Crouzel C, Di Giamberardino L, Pappata S. · 1 INSERM Unit 334, Service Hospitalier Frederic Joliot, CEA/DSV/DRM, Orsay, France and INSERM Unit 324, Paris, France. · Eur J Neurol. · Pubmed #10210906 No free full text.

Abstract: It is unclear whether the palliative effects of tetrahydroaminoacridine (THA) (tacrine, Cognex) on the clinical symptoms of patients affected by Alzheimer's disease (AD) are the result of its inhibitory activity on acetylcholinesterase or on other complex sites of action. In order to investigate the cerebral distribution and kinetics of THA in the human brain in vivo, we performed positron emission tomography (PET) imaging with [11C]N-methyl-tetrahydro-aminoacridine (MTHA) in healthy human volunteers. After intravenous injection, [11C]MTHA crossed the blood-brain barrier and reached its maximum uptake between 10 and 40 minutes, depending on the brain regions. Uptake was higher in the grey matter structures, and lower in the white matter. After this peak, the radioactivity remained quasi- constant until 60 minutes in all regions with a half-life varying from 2.44 hours in the thalamus to 3.42 hours in the cerebral cortex. The ratios of regional to whole cerebral cortex brain radioactivity calculated between 50 and 70 minutes after the tracer injection were 1.14 +/- 0.04, 1.07 +/- 0. 03 and 1.06 +/- 0.04 in the putamen, cerebellum and thalamus, respectively. Overall, these results show that: (1) [11C]MTHA crosses the blood-brain barrier easily and is highly concentrated in the brain; (2) the regional brain distribution of [11C]MTHA does not parallel that of in vivo acetylcholinesterase (AChE) concentrations; and (3) the cerebral kinetics of [11C]MTHA are consistent with known plasmatic pharmacokinetics of THA in AD patients. We conclude that PET imaging with [11C]MTHA is a useful method for assessing the cerebral distribution and kinetics of THA in vivo.

Forette F. · Conseiller Technique Personnes Agées, Ministère de la Santé. · Encephale. · Pubmed #17099582 No free full text.

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Rigaud AS, Latour F, Moulin F, Forette F, Traykov L, Boller F. · No affiliation provided · Arch Gen Psychiatry. · Pubmed #11879173 No free full text.

This publication has no abstract.