Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation.

BACKGROUND: Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES: To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS: We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and café-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS: The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.

[Use of botulinum toxin A in pelvic floor dysfunctions in the elderly: A review]. / Intérêt de la toxine botulinique A dans le traitement des troubles pelvi-périnéaux de la personne âgée.

INTRODUCTION: The present article is the final report of a multi-disciplinary meeting supported by the GRAPPPA (group for research applied to pelvic floor dysfunctions in the elderly). The objective was to conduct a comprehensive review on the role of botulinum toxin A (BonTA) in the treatment of pelvic floor dysfunctions in the elderly. METHODS: The present article, written as a comprehensive review of the literature, combines data issued from the scientific literature with expert's opinions. Review of the literature was performed using the online bibliographic database MedLine (National Library of Medicine). Regarding intra-detrusor BonTA injections, only articles focusing on elderly patients (>65 yo) were included. Regarding other localizations, given the limited number of data, all articles reporting outcomes of BonTA were included, regardless of studies population age. In case of missing or insufficient data, expert's opinions were formulated. RESULTS: Although, available data are lacking in this specific population, it appears that BonTA could be used in the non-fraily elderly patients to treat overactive bladder or even neurogenic detrusor overactivity, with a success rate comparable to younger population at 3 months (88.9% vs. 91.2%), 6 months (49.4% vs. 52.1%) and 12 months (23.1% vs. 22.3%), as well as a significant decrease in number of voids per day (11.4 vs. 5.29 P<0.001) and in the number of pads per day (4.0 vs. 1.3, P<0.01). Furthermore, BonTA is likely to be offered in the future as a treatment of fecal incontinence and obstructed defecation syndrome symptoms. Concerning bladder outlet obstruction/voiding dysfunction symptoms, intra-urethral sphincter BonTA should not be recommended. CONCLUSION: BonTA injections are of interest in the management of various pelvic floor dysfunctions in the elderly, and its various applications should be better evaluated in this specific population in order to further determine its safety and efficacy.

[Cardiovascular adverse effects of antimuscarinics used in the treatment of overactive bladder in the elderly : A review]. / Effets cardio-vasculaires des traitements anticholinergiques à visée vésicale chez la personne âgée : une revue.

AIM: The aim of this study was to review the evidence regarding the cardiovascular effects of urinary anticholinergic drugs in the elderly. METHODS: A literature review was conducted in October 2017 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: In total, 602 articles between March 1964 and October 2017 have been reported, 60 studies were analyzed, 19 were prospective trials. Geriatric population has a high prevalence of cardiovascular diseases (24.4% of heart diseases on 65-74years and 36.9% on ≥75years). More than 20% of the geriatric population has overactive bladder history and 41.43% of them use of antimuscarinic drugs. Evaluating the cardiovascular adverse effects of antimusarinics in the geriatric population is not easy because of exclusion of high-risk patients in trials. However, serious cardiovascular adverse effects were reported like atrial fibrillation, atrioventricular block or torsade de pointe. Further studies are needed especially in the "real life" in order to precise the exact prevalence of such cardiovascular alterations. CONCLUSION: Without conclusive evidence, potential cardiovascular adverse effects of anticholinergic agents used in overactive bladder must lead to a cautious prescription.

[Pathophysiology of detrusor underactivity in the elderly]. / Physiopathologie de l'hypoactivité détrusorienne de la personne âgée.

AIM: The aim of this study was to review the evidence regarding the pathophysiology of detrusor underactivity in the elderly. METHODS: A literature review was conducted in July 2016 using the Medline/Pubmed database limiting the search to works in English or French. RESULTS: The prevalence of detrusor underactivity has been reported to range from 8% to 48% depending on the definition used and the age of the population studied. Current data suggest that aging may itself be a causative factor of detrusor underactivity through myogenic dysfunctions (ultrastructural degeneration of the detrusor muscle) and neurogenic dysfunctions (by degeneration of efferent but mostly afferent innervation mechanisms). Beyond these inherently age-related mechanisms, many comorbidities whose prevalence increase with age (diabetes, bladder outlet obstruction, estrogen deficiency, atherosclerosis, etc.) may be implicated in the development of detrusor underactivity in the elderly. The role played by detrusor overactivity in the appearance of detrusor underactivity must be considered separately as both seem to be the expression of the same condition of the lower urinary tract responding to different stages and secondary to numerous etiopathogenic factors which modulate its progression and clinical expressions. CONCLUSION: Pathophysiology of detrusor underactivity remains poorly understood but seems to imply myogenic and neurogenic factors which are favored, besides the aging per se, by various and numerous comorbidities which prevalence increase with age (diabetes, bladder outlet obstruction…).

One-Step Detection of Monilinia fructicola, M. fructigena, and M. laxa on Prunus and Malus by a Multiplex Real-Time PCR Assay.

Brown rot is an economically important fungal disease affecting stone and pome fruit orchards, as well as harvested fruit during storage and on the market. Monilinia fructicola, M. laxa, and M. fructigena are the main causal agents of this disease and each have a different regulatory status depending on regional regulations. In this study, a new multiplex tool based on real-time polymerase chain reaction was developed to detect the three pathogenic fungi in a single reaction on fruit, twigs, and flowers of Prunus and Malus spp. Species-specific primer-hydrolysis probe combinations were designed to amplify a region located in a previously described MO368 sequenced characterized amplified region marker, and used in a quadruplex format coupled with the 18S Uni universal primer-probe test in order to check the quality of the DNA template. The assay was designed and optimized with the objective to provide high performance values. Experimental data supported its sensitivity, specificity, reproducibility, and robustness. In addition, a set of quality controls was implemented to minimize the risk of false-positive and false-negative results, thus making this new test fit for use in serial analyses and reliable in the framework of official controls.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Discordant sex in monozygotic XXY/XX twins: a case report.

We report a case of discordant phenotypic sex in monozygotic twins mosaic 47,XXY/46,XX: monozygotic heterokaryotypic twins. The twins presented with cognitive and comprehension delay, behavioural and language disorders, all symptoms frequently reported in Klinefelter syndrome. Molecular zygosity analysis with several markers confirmed that the twins are in effect monozygotic (MZ). Array comparative genomic hybridization found no evidence for the implication of copy number variation in the phenotypes. Ultrasound scans of the reproductive organs revealed no abnormalities. Endocrine tests showed a low testosterone level in Twin 1 (male phenotype) and a low gonadotrophin level in Twin 2 (female phenotype) which, combined with the results from ultrasound examination, provided useful information for potentially predicting the future fertility potential of the twins. Blood karyotypes revealed the presence of a normal 46,XX cell line and an aneuploïd 47,XXY cell line in both patients. Examination of the chromosome constitutions of various tissues such as blood, buccal smear and urinary sediment not surprisingly showed different proportions for the 46,XX and 47,XXY cell lines, which most likely explains the discordant phenotypic sex and mild Klinefelter features. The most plausible underlying biological mechanism is a post-zygotic loss of the Y chromosome in an initially 47,XXY zygote. This would result in an embryo with both 46,XX and 47,XXY cells lines which could subsequently divide into two monozygotic embryos through a twinning process. The two cell lines would then be distributed differently between tissues which could result in phenotypic discordances in the twins. These observations emphasize the importance of regular paediatric evaluations to determine the optimal timing for fertility preservation measures and to detect new Klinefelter features which could appear throughout childhood in the two subjects.

[Guidelines concerning urinary incontinence in elderly: construction and validation of GRAPPPA algorithm]. / Recommandations concernant l'incontinence urinaire de la personne âgée : construction et validation de l'algorithme décisionnel GRAPPPA.

OBJECTIVES: Provide guidelines presented as an algorithm for practical evaluation and first line therapy of urinary incontinence in elderly. PATIENTS AND METHODS: Guidelines using formalized consensus guidelines method. These guidelines have been validated by a group of 40 experts quoting proposals, subsequently reviewed by an independent group of multidisciplinary experts (urologist, general practitioner, neurologist, gynecologist, geriatrist, specialist in physical medicine and rehabilitation). RESULTS: By means of 3 rounds of interrogation of the expert panel, GRAPPPA algorithm was constructed. This algorithm take in account both evaluation and first line therapeutic options in the different type of incontinences observed in this population (urge, stress and mixed incontinence). Initial evaluation consists to track down urinary retention (and subsequently fecal stool impaction, use of anticholinergic or morphinic drugs), urinary tract infection and cognitive impairment. Haematuria, bladder-pelvic pain, history of radiotherapy or recent pelvic surgery, lead to refer the patient to a specialized unit. First line therapy is in all the cases pelvic floor training, use of local oestrogenotherapy and dietetic measures. In urge incontinence, anticholinergic drugs may be used. CONCLUSIONS: Implementation of this algorithm may promote best practice in management of urinary incontinence in elderly.

[Impact on cognitive function of anticholinergic drugs used for the treatment of overactive bladder in the elderly]. / Traitement anticholinergique de l'hyperactivité vésicale de la personne âgée et ses impacts sur la cognition. Revue de la littérature.

OBJECTIVES: Describe the central nervous system (CNS) adverse effects of anticholinergic drugs used for the treatment of overactive bladder (OAB) in the elderly. PATIENTS AND METHODS: Relevant data from the literature were identified primarily through a Medline search of articles published through December 2013. The search terms included overactive bladder, central nervous system, elderly, anticholinergic, and antimuscarinic. Articles were chosen for inclusion based on their pertinence to the focus on treatment of OAB in the elderly. RESULTS: Several anticholinergic drugs are available for the treatment of OAB, including oxybutinin, tolterodine, trospium chloride, solifenacine, fesoterodine. Among the agents reviewed, penetration of the blood-brain barrier (as predicted by lipophilicity, polarity, and molecular size and structure) is highest for oxybutinin, lower for tolterodine, solifenacine, and darifenacine, and lowest for fesoterodine and trospium chloride. Unwanted CNS adverse effects depend in part on patient specific variability in pharmacokinetic parameters, blood-brain barrier permeability, degree of cholinergic neuronal degeneration, total anticholinergic drug burden and patient's baseline cognitive status. The spectrum of anticholinergic CNS adverse effects ranges from drowsiness to hallucinations, severe cognitive impairment, and coma. Among the different anticholinergic agents, oxybutinin has been associated with cognitive impairment and trospium chloride and fesoterodine have shown favorable CNS tolerability. CONCLUSIONS: Anticholinergic drugs improve significatively overactive bladder symptoms in older adults. However, potential CNS adverse effects of anticholinergic agents used in OAB must lead to a full evaluation before and during the treatment in order to evaluate benefice, risks and central side effects in this frail population.

Combined effect of heat treatment and ionic strength on the functionality of whey proteins.

A 5% (wt/vol) whey protein isolate (WPI) dispersion (pH 6.5) with different concentrations of NaCl was submitted to dynamic heat treatment. Protein dispersions were characterized as to their rheological properties, particle sizes, morphology, denaturation temperatures, and protein surface hydrophobicity. At low ionic strength (<200 mmol/kg), gel elastic modulus increased and strongest gel stiffness was achieved. High salt concentrations lead to a weaker gel, whereas no gels at all were formed without salt. The gelation temperature was also influenced by ionic strength and an increase in denaturation temperature and thermal stability was also observed by using differential scanning calorimetry. Additionally, heat-induced changes in secondary structures upon salt augmentation were followed by Fourier transform infrared spectroscopy. Secondary structural elements estimations obtained from amide I assignments were correlated with those from amide III assignments. Upon salt increase, no differences in secondary structure were observed without heating, whereas upon heating and without salt increase, the Fourier transform infrared spectroscopy data revealed an increase in intermolecular ß-sheets at the cost of ß-turns and random coils, with no change in α-helical structures. However, NaCl addition along with dynamic heat treatment of WPI dispersion showed a stabilizing effect on the secondary structural elements of both amide I and amide III bands. Whey protein isolate dispersions in water were also characterized by transmission electron microscopy by a spherical shape with 2 populations (6 and 70 nm). Salt increase alone resulted in the formation of denser aggregates, whereas a transition from spherical/compact protein aggregates to linear ones was observed due to combined salt/heat effect. The important size of these edifices was confirmed by microscopy and light-scattering techniques. Moreover, protein surface hydrophobicity related to the number of hydrophobic sites available decreased significantly. Finally, experimental results demonstrated the strong interaction between ionic strength and dynamic thermal treatment on protein functional properties and their careful adjustment could enable the food industry to effectively use WPI as a gelling agent.

Six-month outcome of elderly people hospitalized via the emergency department: the SAFES cohort.

BACKGROUND: The objective of the study was to identify factors predictive of 6-month institutionalization or mortality in frail elderly patients after acute hospitalization. METHODS: A prospective cohort of elderly subjects 75 years and older was set up in nine French teaching hospitals. Data obtained from a comprehensive geriatric assessment were used in a Cox model to predict 6-month institutionalization or mortality. Institutionalization was defined as incident admission either to a nursing home or other long-term care facility during the follow-up period. RESULTS: Crude institutionalization and death rates after 6 months of follow-up were 18% and 24%, respectively. Independent predictors of institutionalization were: living alone (HR=1.83; 95% CI=1.27-2.62) or a higher number of children (HR=0.86; 95% CI=0.78-0.96), balance problems (HR=1.72; 95% CI=1.19-2.47), malnutrition or risk thereof (HR=1.93; 95% CI=1.24-3.01), and dementia syndrome (HR=1.88; 95% CI=1.32-2.67). Factors found to be independently related to 6-month mortality were exclusively medical factors: malnutrition or risk thereof (HR=1.92; 95% CI=1.17-3.16), delirium (HR=1.80; 95% CI=1.24-2.62), and a high level of comorbidity (HR=1.62; 95% CI=1.09-2.40). Institutionalization (HR=1.92; 95% CI=1.37-2.71) and unplanned readmission (HR=4.47; 95% CI=3.16-2.71) within the follow-up period were also found as independent predictors. CONCLUSION: The main factors predictive of 6-month outcome identified in this study are modifiable by global and multidisciplinary interventions. Their early identification and management would make it possible to modify frail elderly subjects' prognosis favorably.

Identifying Frailty in Thermal/Spa Clinical Setting: A Cross-Sectional Study.

Background: No investigation has assessed frailty in the clinical setting of thermal/spa facilities, which often receive older patients with osteo-articular and musculoskeletal conditions. Objective: To examine the prevalence of frailty in older adults receiving thermal/spa treatment and to gather preliminary evidence about the feasibility of integrating geriatric assessments, including frailty, in the routine clinical consultations in spa facilities. Methods: Mixed design, with a quantitative cross-sectional investigation performed among 197 volunteer patients (mean age 73.2 ± 6.4 years-old; 82.2% women) of seven French thermal/spa facilities and a qualitative investigation (semi-structured interviews) with the nine physicians working in the participating facilities. Frailty was defined according to a modified Fried frailty phenotype based on six self-reported criteria (including mobility impairment, nutritional status, and fatigue): individuals meeting ≥3 criteria were considered frail; 1-2 criteria, pre-frail; no criterion, robust. Interviews with the participating physicians on the feasibility of integrating geriatric assessments in routine clinical consultations at spa facilities were recorded and their content, analyzed. Results: Frailty was detected in 112 individuals (56.9%), 26 (13.2%) were considered prefrail, and 59 (29.9%), robust. Regarding the interviews, three physicians indicated the geriatric assessments could be integrated in the routine spa consultations; two, in the consultations of specific/targeted patients, but not in routine; two, only in the context of health education; two, in the context of research protocols. The content of interviews highlighted geriatric assessments provided a better overview of the health/clinical status of the patients. Conclusion: Frailty is very prevalent in older patients of spa facilities. Such facilities may constitute an interesting clinical setting for screening for frailty through the implementation of geriatric assessments.

Puberty and pubertal growth dynamics in children with idiopathic short stature.

OBJECTIVE: As the prognosis for final height is unfavorable for children with idiopathic short stature (ISS), we studied the pubertal growth dynamics in these children, which is a determinant factor in final height. SUBJECTS/METHODS: In a retrospective cohort study, we analyzed the pubertal period, age of puberty and peripubertal growth in 50 children with ISS. RESULTS: The onset of puberty occurred later. Growth rate tended to become increasingly subnormal in the prepubertal period and height was -2.45 SD at puberty onset. Growth reaccelerated at this point, which tended to correct the deviation from the mean height, but it was insufficient to obtain a normal final height. CONCLUSIONS: The dynamics of growth in children with ISS showed a distinct pattern in the prepubertal and pubertal periods and puberty is significantly delayed in this population. These patterns could explain the unfavorable prognosis for children with ISS.

Fingertip nail bed injuries in children: Comparison of suture repair versus glue (2-octylcyanoacrylate) with 1-year follow-up.

The main objective of this study was to compare the medium-term results of nail bed repair in children using glue (2-octylcyanoacrylate) versus absorbable sutures. The secondary objective was to compare the results of treatment in the emergency room versus the operating room. This retrospective review of 74 fingertip nail bed lacerations (68 children) evaluated the appearance and pain at the last follow-up visit (minimum of 1 year), and the operating time. Mean age was 3.3 years at time of injury (range 10 months-13 years), with a mean follow-up of 2.6 (1-7) years. Thirty-six nail beds were repaired with glue; 38 were sutured. The clinical outcomes in the two groups were similar. The rate of nail dystrophy was 14% (5% major) regardless of the technique. Nail bed repair time was significantly shorter in the glue group (10.2 vs. 20.3min, p<0.001). Forty-five repairs were performed in the operating room and 29 in the emergency room. The complication rate (early infections) was significantly higher in patients treated in the emergency room. Tissue adhesive (2-octylcyanoacrylate glue) is a reliable option for repairing nail bed lacerations, both in terms of outcomes and speed of repair. Treatment in the operating room is preferable.

[Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly]. / Troubles de la déglutition du sujet âgé et pneumopathies en 14 questions/réponses.

Swallowing disorders (or dysphagia) are common in the elderly and their prevalence is often underestimated. They may result in serious complications including dehydration, malnutrition, airway obstruction, aspiration pneumonia (infectious process) or pneumonitis (chemical injury caused by the inhalation of sterile gastric contents). Moreover the repercussions of dysphagia are not only physical but also emotional and social, leading to depression, altered quality of life, and social isolation. While some changes in swallowing may be a natural result of aging, dysphagia in the elderly is mainly due to central nervous system diseases such as stroke, parkinsonism, dementia, medications, local oral and oesophageal factors. To be effective, management requires a multidisciplinary team approach and a careful assessment of the patient's oropharyngeal anatomy and physiology, medical and nutritional status, cognition, language and behaviour. Clinical evaluation can be completed by a videofluoroscopic study which enables observation of bolus movement and movements of the oral cavity, pharynx and larynx throughout the swallow. The treatment depends on the underlying cause, extent of dysphagia and prognosis. Various categories of treatment are available, including compensatory strategies (postural changes and dietary modification), direct or indirect therapy techniques (swallow manoeuvres, medication and surgical procedures).

[Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology]. / Recommandations pour la prise en charge du cancer de la prostate chez l'homme âgé : un travail du comité de cancérologie de l'association française d'urologie.

The increase in life expectancy combined with the increase in the global incidence of cancers will probably results in an increase in the number of cancers observed in the elderly. The increase in the incidence of prostate cancers in geriatric patients (45% of prostate cancers are diagnosed after 75 years old) is in sharp contrast with the lack of strong scientific data on the topic. By the meantime, oncogeriatrics has been developing for some years now under the guidance of the International Society of Oncogeriatrics. Such an approach aims at palliating the low quality of care of cancers in geriatric patients. The reasons for the low quality of care come from the characteristics of these patients and from the training of the care providers. The authors recall the principles of oncogeriatric evaluation and the classification of patients as it is actually proposed. They describe the main treatments and their results in the geriatric population and they describe the decision process concerning the choice of the treatment. They also suggest some guidelines on the diagnosis of prostate cancer, evaluation of the patients and the treatments of the disease in the elderly. Prostate cancer is almost the perfect model for oncogeriatrics. Urologists should remain the corner stone of its management, whatever the age of their patient.

Derivation and validation of a mortality-risk index from a cohort of frail elderly patients hospitalised in medical wards via emergencies: the SAFES study.

To identify predictive factors for 2-year mortality in frail elderly patients after acute hospitalisation, and from these to derive and validate a Mortality Risk Index (MRI). A prospective cohort of elderly patients was set up in nine teaching hospitals. This cohort was randomly split up into a derivation cohort (DC) of 870 subjects and a validation cohort (VC) of 436 subjects. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 2-year mortality and to identify risk groups for mortality. A ROC analysis was performed to explore the validity of the MRI. Five factors were identified and weighted using hazard ratios to construct the MRI: age 85 or over (1 point), dependence for the ADL (1 point), delirium (2 points), malnutrition risk (2 points), and co-morbidity level (2 points for medium level, 3 points for high level). Three risk groups were identified according to the MRI. Mortality rates increased significantly across risk groups in both cohorts. In the DC, mortality rates were: 20.8% in the low-risk group, 49.6% in the medium-risk group, and 62.1% in the high-risk group. In the VC, mortality rates were respectively 21.7, 48.5, and 65.4%. The area under the ROC curve for overall score was statistically the same in the DC (0.72) as in the VC (0.71). The proposed MRI appears as a simple and easy-to-use tool developed from relevant geriatric variables. Its accuracy is good and the validation procedure gives a good stability of results.

Frailty, osteoporosis and hip fracture: causes, consequences and therapeutic perspectives.

OBJECTIVE: The aim of this review of the literature is to report the factors which both contribute to the frailty syndrome and increase hip fracture risk in the elderly. This work is the fruit of common reflection by geriatricians, endocrinologists, gynecologists and rheumatologists, and seeks to stress the importance of detection and management of the various components of frailty in elderly subjects who are followed and treated for osteoporosis. It also sets out to heighten awareness of the need for management of osteoporosis in the frail elderly. DESIGN: The current literature on frailty and its links with hip fracture was reviewed and discussed by the group. RESULTS: The factors and mechanisms which are common to both osteoporosis and frailty (falls, weight loss, sarcopenia, low physical activity, cognitive decline, depression, hormones such as testosterone, estrogens, insulin-like growth factor-I (IGF-I), growth hormone (GH), vitamin D and pro-inflammatory cytokines) were identified. The obstacles to access to diagnosis and treatment of osteoporosis in the frail elderly population and common therapeutic pathways for osteoporosis and frailty were discussed. CONCLUSION: Future research including frail subjects would improve our understanding of how management of frailty can can contribute to lower the incidence of fractures. In parallel, more systematic management of osteoporosis should reduce the risk of becoming frail in the elderly population.

Prevention of progression to dementia in the elderly: rationale and proposal for a health-promoting memory consultation (an IANA Task Force).

Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

IANA task force on nutrition and cognitive decline with aging.

Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta analyses should be developed, and on the basis of their results the most appropriate interventional studies can be planned. These studies must control for the greatest number of known confounding factors and take into account the impact of the standard social determinants of food habits, such as the regional cultures, social status, and educational level.