Adapted Home-Based Exercises in Dementia: An Exploratory Pre-post Pilot and Feasibility Study.

The goals of this exploratory pre-post pilot and feasibility study (NCT04916964) were to assess the feasibility and effectiveness of an adapted Test-and-Exercise home-based exercise program on basic functional mobility and executive functions in persons with prodromal or mild Alzheimer's disease. Participants followed an 8 week exercise program at home, once per week with a physiotherapist and twice per week with their usual caregiver or independently. Functional mobility and executive functions were assessed before and after the intervention. Feasibility criteria were recruitment opportunity, participation agreement rate, cost adequacy, and drop-out rate. Twelve participants aged 80.83 ± 4.65 years took part in the study. All the basic functional mobility measures showed small effect sizes. Concerning executive functions, 5 measures showed small to moderate effect sizes. The 4 feasibility criteria were met. A larger scale study would, however, need adaptations and prior research on the ability of this population to use touch-screen technology.

[Capgras delusion and Alzheimer disease]. / Syndrome de Capgras et maladie d'Alzheimer.

Capgras delusion is classified with the misidentification syndromes. In dementia it associates cognitive deficiency of memory and facial recognition (prosopoagnosia) with delirious idea of substitution by a double. The first reported case in the paper describes the important affective and comportmental reactions due to the identification of a double perceived as an imposter, affecting both the suffering person and his family. Rarely, as reported in the second case, misrecognition concerns the person itself (autoprosopagnosia) who can have the illusion to be in front of a twin brother (« auto-Capgras ¼). We discuss data from the literature concerning prevalence, results of cerebral imaging and functional prognosis associated with this curious syndrome.

Le syndrome de Capgras fait partie des troubles de l'identification des personnes. Dans la démence, il associe des déficits cognitifs de la mémoire et de la reconnaissance des visages (prosopagnosie) et des idées délirantes de substitution par des sosies. La première situation rapportée dans l'article décrit les importantes réactions affectives et comportementales engendrées par l'identification d'un sosie qui est perçu comme un imposteur, affectant à la fois le malade et son entourage. Rarement, comme rapporté dans la deuxième situation, la fausse reconnaissance concerne la personne elle-même (autoprosopagnosie) qui peut avoir l'illusion d'avoir en face d'elle un frère jumeau (« auto-Capgras ¼). Nous discutons de données issues de la littérature concernant la prévalence, les résultats de l'imagerie cérébrale ainsi que le pronostic fonctionnel liés à ce curieux syndrome.

Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance.

AIMS: A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting. METHODS: A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1. RESULTS: The average donepezil clearance was 7.3 l h(-1) with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers. CONCLUSION: The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.

Relationship of CYP2D6, CYP3A, POR, and ABCB1 genotypes with galantamine plasma concentrations.

BACKGROUND: The frequently prescribed antidementia drug galantamine is extensively metabolized by the enzymes cytochrome P450 (CYP) 2D6 and CYP3A and is a substrate of the P-glycoprotein. We aimed to study the relationship between genetic variants influencing the activity of these enzymes and transporters with galantamine steady state plasma concentrations. METHODS: In this naturalistic cross-sectional study, 27 older patients treated with galantamine were included. The patients were genotyped for common polymorphisms in CYP2D6, CYP3A4/5, POR, and ABCB1, and galantamine steady state plasma concentrations were determined. RESULTS: The CYP2D6 genotype seemed to be an important determinant of galantamine pharmacokinetics, with CYP2D6 poor metabolizers presenting 45% and 61% higher dose-adjusted galantamine plasma concentrations than heterozygous and homozygous CYP2D6 extensive metabolizers (median 2.9 versus 2.0 ng/mL · mg, P = 0.025, and 1.8 ng/mL · mg, P = 0.004), respectively. CONCLUSIONS: The CYP2D6 genotype significantly influenced galantamine plasma concentrations. The influence of CYP2D6 polymorphisms on the treatment efficacy and tolerability should be further investigated.

Population pharmacokinetic study of memantine: effects of clinical and genetic factors.

BACKGROUND AND OBJECTIVE: Memantine, a frequently prescribed anti-dementia drug, is mainly eliminated unchanged by the kidneys, partly via tubular secretion. Considerable inter-individual variability in plasma concentrations has been reported. We aimed to investigate clinical and genetic factors influencing memantine disposition. METHODS: A population pharmacokinetic study was performed including data from 108 patients recruited in a naturalistic setting. Patients were genotyped for common polymorphisms in renal cation transporters (SLC22A1/2/5, SLC47A1, ABCB1) and nuclear receptors (NR1I2, NR1I3, RXR, PPAR) involved in transporter expression. RESULTS: The average clearance was 5.2 L/h with a 27 % inter-individual variability (percentage coefficient of variation). Glomerular filtration rate (p = 0.007) and sex (p = 0.001) markedly influenced memantine clearance. NR1I2 rs1523130 was identified as the unique significant genetic covariate for memantine clearance (p = 0.006), with carriers of the NR1I2 rs1523130 CT/TT genotypes presenting a 16 % slower memantine elimination than carriers of the CC genotype. CONCLUSION: The better understanding of inter-individual variability of memantine disposition might be beneficial in the context of individual dose optimization.

[Preventive approaches to dementia]. / Approche preventive des pathologies démentietlles.

Prevalence and incidence of dementia increase with demographic aging. Benefits of current antidementia drugs are modest, both in cognitive and functional domains. Therefore, interest is growing to evaluate the effects of interventions aiming at preventing cognitive decline and, ideally, dementia onset. Cognitive training and physical activity seem promising. This paper describes recent studies that assessed the benefits of preventive strategies in the domain of dementia, especially in Alzheimer's disease.

[What's new in geriatric medicine]. / Gériatrie.

Several studies clarified the role of different interventions such as vitamine D replacement, denosumab treatment, and vertebroplasty in the prevention and management of falls and fractures. A trial tested the effectiveness of pharmaceutical assistance at the time of discharge, emphasizing the potential benefits for the patients and the health care system. Syncopal episodes frequently lead to hospital admission. A retrospective study evaluated the diagnostic yield of different tests and emphasized the importance to actively seek orthostatic hypotension in older patients. Finally, advances remain modest in the field of dementias.

Are circulating endothelial-derived and platelet-derived microparticles a pathogenic factor in the cisplatin-induced stroke?

BACKGROUND AND PURPOSE: To evaluate whether cisplatin-induced stroke is mediated by vascular toxicity with release of prothrombotic endothelial and platelet-derived microparticles (MPs). METHODS: Endothelial (CD31(+)CD41(-)), platelets (CD31(+)CD41(+)) and prothrombotic (Annexin V(+)) circulating MPs were quantified by flow cytometry in 18 patients with cancer, before and 3 days after administration of cisplatin, and compared with 18 healthy controls. Thrombin-antithrombin complex and prothrombin fragments (F(1+2)) were measured as markers of the activation of the coagulation. RESULTS: In patients with cancer, baseline levels of circulating prothrombotic, endothelial and platelet-derived MPs were similar to healthy controls and decreased significantly after administration of cisplatin. High-baseline MPs levels were observed in 5 patients who received cisplatin for a second or third cycle. A high-baseline activation of the coagulation was observed in all patients without further increase after cisplatin infusion. CONCLUSIONS: Cisplatin treatment is immediately followed by a decrease in circulating levels of endothelial and platelet-derived MPs. However, a transient increase in MPs is observed at the second and third infusion, and this may contribute to the cisplatin-induced stroke.

Effect of mild endurance exercise training and pravastatin on peripheral vasodilatation of forearm resistance vessels in patients with coronary artery disease.

BACKGROUND: Improved endothelial function may contribute to the beneficial effects of cholesterol lowering therapy in patients with coronary artery disease (CAD), but results of the effect of statin therapy on endothelial function are disparate in these patients. Exercise training has been reported to improve endothelial function of patients at risk of or with established CAD. The goal of the study was to compare the effect of mild exercise training or statin therapy on forearm endothelial function in CAD patients with average cholesterol levels. DESIGN AND METHODS: Twenty-eight sedentary male patients with angiographically documented CAD and average pretreatment total plasma cholesterol levels (5.1+/-0.9 mmol/l) aged 42-75 years were included. They were randomly assigned in a 2 : 1 order to either statin therapy (pravastatin, 40 mg daily) or exercise training therapy (mild endurance exercise three or more times a week). The effects of 10 weeks of either treatment on endothelium-dependent and independent vasodilation of forearm resistance vessels was assessed by plethysmography. Cardiopulmonary exercise testing was performed at baseline and after 10 weeks. RESULTS: Ten weeks of pravastatin therapy significantly reduced low-density lipoprotein cholesterol (from 3.8+/-0.6 to 3.1+/-0.6 mmol/l at study end, P=0.04) and the ratio of total to high-density lipoprotein cholesterol (from 4.9+/-0.8 to 3.7+/-0.7 mmol/l, P=0.002). Exercise training did not significantly modify the lipid profile. Peak oxygen consumption, maximal achieved workload and exercise duration tended to improve in the exercise training group but remained unchanged in the pravastatin-treated group. Neither 10 weeks of pravastatin nor mild endurance exercise training improved endothelium-dependent or independent vasomotor function in forearm resistance vessels. CONCLUSIONS: In patients with CAD and average cholesterol levels, 10 weeks of treatment with mild endurance exercise training or with pravastatin failed to improve endothelium-dependent or independent vasomotor function in forearm resistance vessels.