How to design nutritional intervention trials to slow cognitive decline in apparently healthy populations and apply for efficacy claims: a statement from the International Academy on Nutrition and Aging Task Force.

Interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1- Risk- reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2- Innovative study designs are needed to improve the quality of these studies.

[Mini-Mental State Examination:a useful method for the evaluation of the cognitive status of patients by the clinician. Consensual French version]. / Le Mini-Mental State Examination (MMSE): un outil pratique pour l'évaluation de l'état cognitif des patients par le clinicien. Version française consensuelle. Groupe de Recherche sur les Evaluations Cognitives (GRECO).

A PRACTICAL TOOL: Screening for cognitive deficiency has been considerably improved by the use of a standardized tool, the Mini-Mental State Examination (MMSE). The MMSE only takes a few minutes and furnishes quantitative data for comparison between patients and to follow the evolution of a given patient. AN IMPORTANT ROLE: The MMSE is particularly useful for screening for dementia and states of mental confusion. It should be used systematically for elderly subjects, not only in the neurology setting, but also in geriatrics, psychiatrics and internal medicine. INTERPRETATION: The global score gives an assessment of the subject's performance level, taking into account for age, affective status and cultural situation. The MMSE cannot alone provide the diagnosis of dementia which requires a complete neurological examination. THE CONSENSUAL FRENCH VERSION: Diverse French versions have been developed with considerable differences in scoring schemes. For this reason, the Working Group on Cognitive Evaluations (GREC) has established a consensual version of the MMSE in French.

[Viewpoint on the methodology of drug trials affecting cognition of elderly patients]. / Point de vue sur la méthodologie des essais de médicaments à visée cognitive chez les sujets âgés.

Clinical trials for cognitive disorders in the elderly require specific methodological guidelines. They must take into account the psychosocial dimension of the patient and his family and must be based on serious neurobiologic knowledge. In degenerative dementias the progress of research concern genetics, molecular intercellular recognition and astrocytic cells. Biology of cognition like hippocampal long term potentiation provides good pharmacologic basis for trials. In normal brain aging several ways must be developed: aminergic systems, free radicals, excitotoxic amino-acid, nerves growth factors. Clinical trials bring informations for pharmacology and epidemiology. Cholinergic neurons are the main pharmacologic target but there are many other ones: GABA-ergic system, Tau protein, amyloid. A rigourous selection of patients allows to precise the nosology of illness responsible of cognitive disorders and to point-out early clinical signs that represent a more sensitive target. Diagnostic criteria are useful in Alzheimer's disease, memory impairment, vascular dementias and other dementias. Evaluation of stage and evolution of dementia, comorbidity, limits of age and caregiver are practical problems. The effects of drugs used to treat cognitive functions are subtle so it is necessary to detect them to choose the best tests in function of each trial. Laboratory investigations can be used to evaluate the response to drug administration. Ethical point of view is represented by the fact that old people with cognitive impairment must not be away from therapeutic progress. In this field we must consider carefully the consequences of cognitive impairment on patient judgment and consent to clinical trial. Legal problems are regulated by supranational rules and French directives of Huriet law.

[Evaluation of labetalol in general medicine in aged patients with hypertension. Compliance, efficacy and safety in long-term treatment]. / Evaluation du labétalol en médecine générale chez l'hypertendu âgé. Observance, efficacité et tolérance au long cours.

The efficacy and the clinical and biological safety of labetalol were assessed, in primary care, in an ambulatory hypertensive elderly population, with systolo-diastolic hypertension (mean 175 +/- 14/100 +/- 7 mmHg) monitored during a 6 month period by general practitioners. Two hundred and sixty six of the 309 patients recruited (86%) completed the study, with satisfactory compliance. Mean blood pressure reduction after six months treatment was 27.6/17.7 mmHg and 25.9/17.4 mmHg (p less than 0.001) supine and standing respectively; and 75 p. cent of the patients who tolerated the treatment had their blood pressure normalized (BP less than 160/95 mmHg) with monotherapy by labetalol, posology ranging from 100 to 200 mg b.i.d. in 9/10th of them. Maximal antihypertensive effect, almost obtained within 4 months of treatment, was equivalent in smokers and non smokers (blood pressure normalization 84% vs 74.4%, p = 0.29) and less in obese patients compared to non obese (68% vs 80%, p less than 0.05). Drug withdrawal rate for side effects was only 7.4 p. cent and clinical and biological tolerance to labetalol was satisfactory in most patients. This 6 month survey in primary care confirmed the efficacy of monotherapy by labetalol in elderly hypertensive patients, and good compliance to treatment with a drug well tolerated in this population.

[Ambulatory treatment with cefuroxime-axetil of infectious bronchitis in patients sixty years of age or older: comparative study of the combination of amoxicillin and clavulanic acid]. / Traitement ambulatoire par le céfuroxime-axetil des bronchites infectieuses du sujet de soixante ans ou plus: étude comparative avec l'association d'amoxicilline et d'acide clavulanique.

The aim of this multicenter, prospective randomized trial was to compare the efficacy and safety of cefuroxime-axetil and amoxycillin/clavulanic acid for the treatment of infectious bronchitis in the elderly patient. Between January and April 1989, 157 out patients aged 60 years or more and presenting with infectious bronchitis were treated with either cefuroxime-axetil (250 mg bid), or the association amoxycillin/clavulanic acid (500 mg/125 mg bid). The two treatment groups were comparable at the time of inclusion; the mean age was 70 years, 82% of the patients were febrile, 75% presented purulent expectoration, 24% had a history of chronic bronchitis and 19% received symptomatic treatment was NSAIDs. The mean duration of treatment was 9 days. Clinical efficacy was assessed by the investigators. While fever and cough resolved similarly in the two groups, statistically fewer patients presented persistent purulent expectoration in the cefuroxime-axetil treatment group than in the group receiving amoxycillin/clavulanic acid (2% and 13%, respectively, p = 0.03). The proportion of patients who reported at least one side-effect was 3.6% in the cefuroxime-axetil treatment group against 21.6% of those who received the association (p = 0.006).

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

[Administration of terfenadine in a single dose: comparison to standard treatment, as a double blind study, in patients presenting with allergic rhinitis]. / Administration de la terfénadine en prise unique: comparaison au traitement standard, en double aveugle, chez des patients présentant une rhinite allergique.

This double-blind, randomized multicentre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.

[Preventive action of an immunomodulator on respiratory infections in elderly subjects]. / Action préventive d'un immunomodulateur sur les infections respiratoires de sujets âgés.

Three hundred and fourteen elderly subjects admitted to chronic medical centers were given either RU 41740 (n = 155) or a placebo (n = 159) at the rate of one course per month during three months. RU 41740 was administered in doses of 2 mg per day during 8 days in the first course and 1 mg per day during 8 days in the second and third courses. The subjects were followed up and regularly examined every three months for one year. The incidence of acute infectious episodes was evaluated in both groups. Compared to those patients who received the placebo, the number of subjects without infection was significantly higher in the treated group during the 0-6 months and the 0-9 months periods and during the 12 months of observation. The number of infectious episodes was reduced during the 0-3 months and 0-9 months periods and throughout the 12 months of the trial. The mean duration of pulmonary infections that occurred during the 0-6 and 0-9 months periods was reduced. Finally, there was a significant decrease in the duration of antibiotic therapy during the 0-3, 0-6, 0-9 months periods and during the 12 months of observation. The drug was well tolerated. This study showed that RU 41740 is effective in protecting elderly and therefore fragile subjects against respiratory infections.

Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever.

This double-blind, randomized multi-centre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.

A double-blind comparison of terfenadine and mequitazine in the symptomatic treatment of acute pollinosis.

This study was a double-blind, parallel group comparison of terfenadine (TRF) 60 mg b.i.d. and mequitazine (MQZ) 5 mg b.i.d. for 7 days in the symptomatic treatment of acute pollinosis. The trial took place in the same geographic area and during the same pollen season (May-July 85), to ensure homogeneity of the study population. The fourteen investigators participating in this multicentre trial recruited 141 patients (69 TRF; 72 MQZ) suffering from well-documented pollinosis, mainly hay fever and sometimes allergy to tree pollens. Symptoms (nasal itching, sneezing, rhinorrhoea, obstruction, conjunctivitis) and possible somnolence were rated daily using a 4-point rating-scale of 0 to 3 by the patient on a diary card. Assessment of over-all efficacy and tolerability - focusing on atropinic side-effects - was made at the end of the seven-days treatment period by the physician, after reviewing the diary card and questioning the patient. The means score profile of each symptom for the study period was similar with the two treatments. Both had a fast onset of action with the regression of the total symptoms' score being already significant at day 1. Over-all assessment of efficacy at day 7 showed no significant difference between the two treatments. The daily somnolence scores however showed a clear and significant difference between the two drugs: the frequency of moderate to marked somnolence from day 2 to 7 was around 15% with MQZ and around 5% on days 2 to 5 and 0% on days 6 and 7 with TRF, the difference being significant on days 2, 5, 6 and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Directive principles for trials of cerebrally-acting drugs to be performed by groups of general practitioners. / Principes directeurs de l'expertise de médicaments à visée cérébrale réalisée avec des groupes de médecins praticiens.

The authors explain why clinical trials of drugs acting on the brain should be carried out in ambulatory geriatric patients by groups of general practitioners. On the basis of their experience, they endeavour to lay down the basic principles and conditions required for such trials.

[A clinical rating scale for personality. Its validation through factor analysis in geriatrics (author's transl)]. / Echelle clinique d'évaluation de la personnalité. Validation par analyse factorielle en gériatrie.

A rating scale has been established in our department. It is used to assess different psychological aspects. It can be applied in treatment trials as well as to provide a descriptive study of personality or behaviour. 26 two-pole items at five levels are covered by this scale. A factor analysis was used to validate the scale on a population of old people in institutional care. This showed the scale evaluates one general factor and nine group factors: affective maturity, social ease, inhibition, social adaptation, anxiety depression, psychic well-being, psychopathic tendencies, extraversion and receptivity, guilt-feeling. To appreciate the effects of psychotropic drugs on behaviour, these ten factors can be grouped into three: a factor we can call "mental health", a factor of social adaptation, an affective-emotional factor.