Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

UNLABELLED: Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. OBJECTIVES: The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). RESULTS: Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. CONCLUSION: Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

IAGG workshop: health promotion program on prevention of late onset dementia.

IAGG, WHO, and SFGG organized a international workshop on Health promotion programs on prevention of late on-set dementia. Thirty world specialists coming from Europe, North America, Asia, South America, Africa and Australia, shared their experience on methods and results of large epidemiological interventions to reduce incidents of dementia or delay its on-set. Chaired by Laura FRATIGLIONI, an expert in Epidemiological studies on dementia issues, the workshop gave opportunity for discussions and controversies about the state-of-the-art. Based on different national and international trials (ADAPT, MAPT, FINGER, GUDIAGE, GEM etc) the questions remained opened for different aspects of methodology, the choice of domain or multi domain intervention, the choice and the definition of the target populations, the best age of candidates, the issues related to the discrepancy between late effects, and interventions' duration. We are please to publish in the Journal, the presentations presented to this workshop. These publications will complete previously task force published in the journal in the last two years on methodological issues for Alzheimer's trials including end point, biomarkers, and the experience of past therapeutic trials.

[Diagnosis of dementia]. / Démarche diagnostique devant un syndrome démentiel.

PURPOSE: The high prevalence of dementia, particularly of Alzheimer's disease, the increase of their incidence with age, and the population aging make this group of diseases a major problem for public health. Nevertheless, diagnosis is difficult because it depends on evolution of disturbances that patients often cannot precisely relate, on complex neuropsychological explorations, and on pathological examination difficult to obtain. Today in France, geriatricians are fully implicated in the diagnosis of dementia and all the physicians who give care to elderly, should lead easily a diagnosis of dementia. CURRENT KNOWLEDGE AND KEY POINTS: In February 2000 ANAES (French governmental agency for accreditation and evaluation of health system) published recommendations called "practical recommendations for the diagnosis of Alzheimer's disease". These recommendations allow physicians to standardize their practices and consist of a rigorous clinical history and examination, a neuropsychological analysis, standard investigations and application of diagnostic criteria already widely diffused and used. FUTURE PROSPECTS AND PROJECTS: Deepening of knowledge, in particular in the domains of neuropsychology and functional cerebral imagery, should allow physicians to diagnose early dementia. These early diagnosis should allow to initiate a multidisciplinary, preventive and effective care for patients. Specific drugs, that will be available, will be intended mostly for patients with early diagnosis, ideally at a pre-dementia state.

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients.

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.

[Clinical features of ambulatory patients over 80 years of age followed for Alzheimer's disease. French prospective multicenter study REAL.FR]. / Caractéristiques cliniques des patients ambulatoires âgés de plus de 80 ans suivis pour une maladie d'Alzheimer. Etude française multicentrique prospective REAL.FR.

PURPOSE: Twice out off three, patients with Alzheimer's disease (AD) are aged 80 and older. Very old patients are more frail, have social precariousness and have often polypathology. Few data are available about these elderly patients. The aim of our study was to analyse characteristics of AD patients aged 80 and older. MATERIAL AND METHODS: This is a prospective, multicentric French study (REAL.FR) of a cohort of ambulatory AD patients, with Mini-Mental State values between 10 and 26. Clinical and social data at inclusion of patients aged 80 and older and patients younger were compared. RESULTS: Six hundred eighty nine patients (488 women, 201 men) were included between April 2000 and June 2002. The mean age was 77.8 +/- 6.9 years. Two hundred sixty four patients (38%) were aged 80 and older. Those patients were more dependant for Activities of Daily Living (ADL) than younger patients (ADL score of Katz: 5.2 +/- 1.07 et 5.6 +/- 0.74 respectively; p < 0.001 and IADL (Instrumental Activities of Daily Living) score of Lawton: 7.3 +/- 3.57 et 9.3 +/- 1.57 respectively; p < 0.001). Duration of evolution of the disease were comparable between older and younger patients. CONCLUSION: In our cohort, AD patients aged 80 and older had a weakest autonomy for the ADL than younger patients with the same stage of the disease. Results has implications on care. Following the cohort will permit to specify evolution of data.

[Determination of regimen fluindione needed for anticoagulation in the elderly]. / Schéma simple d'adaptation posologique de la fluindione chez les patients âgés.

INTRODUCTION: There is no validated method to predict the daily maintenance dosage of oral anticoagulation treatment by fluindione in the elderly patients. The aim of our prospective study was to look for a relation between INR at day 2 after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3. PATIENTS AND METHODS: Ten milligrams of fluindione were administered on first and second day of treatment. INR was determined the third day. RESULTS: From this value, we were able to determine the daily dosage of fluindione (+/- 5mg) that maintained a steady state INR value between 2 and 3. CONCLUSION: In these very elderly patients, there was a relation between INR at the third day after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3.

The effect of gamma-linolenic acid on plasma and membrane lipids and renal prostaglandin synthesis in older subjects.

UNLABELLED: Senescence is associated with a decreased activity of enzyme delta-6 desaturase, which converts linoleic acid to gamma-linolenic acid. This enzymatic defect may alter the composition of plasma and membrane lipids, and influences the biosynthesis of renal prostaglandins. Exogenous supplementation of GLA during 3 months increases the plasma level of dihomo-gamma-linolenic acid (p < 0.002), and to a smaller degree, the level in erythrocyte membrane lipids. This treatment was associated with a beneficial reduction of cardiovascular risk factors (arterial hypertension, total cholesterol, apolipoprotein B, HDL-cholesterol, apolipoprotein A-I) and the renal function has become stable reached. Epogam treatment also increased the biosynthesis of renal prostaglandins, especially that of prostaglandin E2, which has a vasodilatory effect on vessel walls and reduces the elevated blood pressure. CONCLUSION: Dietary supplementation of essential fatty acids such as gamma-linolenic acid to old subjects has beneficial effect on their health condition. (Tab. 6, Fig. 5, Ref. 37.)

[Neuropathology of the cerebral vessels of centenarians]. / Neuropathologie des vaisseaux cérébraux des centenaires.

Neuropathological study of brain and brain vessels was performed in two series of 12 and 20 centenarians, focusing on the prevalence of small vessel lesions, infarction, Alzheimer's changes and mental status. These are discussed as a function of vascular risk factors. In the first series (12 cases), there was no correlation between the severity of small vessel lesions: hyalinosis (12/12), mineralisation (10/12), amyloid angiopathy (9/12), vascular risk factors (high blood pressure or diabetes), Alzheimer's lesions. However, there was a tendency for an association between amyloid angiopathy and high density of neurofibrillary tangles. In the second series (20 cases), small infarcts and lacunes were found in 9/20 cases, neurofibrillary tangles and diffuse deposits of A beta peptide were constant, senile plaques were very frequent (19/20). Five patients were demented (one vascular dementia, one Alzheimer dementia, and 3 mixed dementias). These data indicate that: 1) Lesions of the walls of small cerebral vessels do not seem linked to the vascular risk factors observed at the end of the life of centenarians. 2) Cerebral infarcts and lacunes are frequent in these patients, and are responsible, at least in part, for a high proportion of the cognitive dysfunctions. The study of larger series is needed for a better understanding of relationships between vascular and degenerative lesions in the oldest old.

Hypertension in older adults.

The high prevalence of hypertension in older persons (nearly one of two subjects aged 60 years and older) suggests that the recognition and treatment should be a priority for physicians. Although diastolic blood pressure is regarded as an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of cerebrovascular disease, congestive heart failure, and coronary heart disease, which are the major causes of cardiovascular morbidity and mortality in the population aged older than 65 years. Controlled, randomized trials have shown that treatment of systolic as well as systolodiastolic hypertension decreases the incidence of cardiovascular and cerebrovascular complications in older adults. The question of whether treatment of hypertension should be maintained in very old persons, those older than 80 years, is still undecided.

Does the benefit of antihypertensive treatment outweigh the risk in very elderly hypertensive patients?

The risk of hypertension and the benefits of antihypertensive treatment are well established in older patients aged up to 80 years. For people aged 85 and over, data are scarce and conflicting. A positive association between blood pressure and survival has been found in several cohort studies; this relationship held true after adjustment for many factors in some studies, but disappeared after adjustment for indicators of poor health in others. In randomized trials, the benefit of antihypertensive treatment was demonstrated in the Systolic Hypertension in the Elderly Program (SHEP) study, but it declined with age and was not observable after 80 years in the European Working Party on High Blood Pressure in the Elderly (EWPHE) study. The SYSTolic hypertension in elderly in EURope Trial (SYST-EUR) study evidenced a benefit on cardiovascular morbidity but not on mortality. People who reach a very old age share some characteristics that make them different from those '60 (or 65) and over' and justify special studies which are currently in progress. In the meantime, any treatment decision can only rely on extrapolations moderated by common sense, but the already demonstrated favorable results on morbidity argue against a threshold beyond which hypertension should not be treated.

Preservation of midbrain catecholaminergic neurons in very old human subjects.

Parkinson's disease is characterized by a progressive degeneration of dopaminergic neurons in the midbrain, yet the cause of this neuronal loss is still unknown. It has been hypothesized that Parkinson's disease could be the consequence of accelerated ageing. In order to reveal a possible common process during ageing and Parkinson's disease neurodegeneration, catecholaminergic neurons of five anatomical regions of the brainstem (substantia nigra, central grey substance, ventral tegmental area, peri- and retrorubral area, and locus coeruleus) have been quantified using immunohistochemical staining for tyrosine hydroxylase (TH) on regularly spaced sections, between the rostral and caudal poles of the mesencephalon and in the rostral pole of the pons, in post-mortem samples of 21 control subjects who died at ages 44-110 years. No statistically significant loss of TH positive neurons was observed in the older subjects, either in the substantia nigra or in the other midbrain regions that are known to degenerate to a lesser degree in Parkinson's disease. Furthermore, in the later regions no neuronal loss was observed from age 44 to 80 years, indicating that this result is not dependent on the inclusion of 'supernormal' very old people. These results suggest that from age 44 to 110 years, ageing in control adults is not, or is scarcely, accompanied by catecholaminergic cell loss in the midbrain and hence Parkinson's disease is probably not caused by an acceleration of a degenerative process during ageing.

Hypertension in very old subjects.

The role of hypertension as a risk factor for mortality and cardiovascular morbidity and the benefits of antihypertensive treatment are well established in older patients up to 80 years. For people aged 85 and over, who are the most rapidly growing segment of population in developed countries, data are scarce and conflicting. A positive association between blood pressure and survival has been found in several cohort studies, and this relation held true after adjustment for many factors. In randomized trials, the benefits of antihypertensive treatment declined with age and were not observable after 80 years, with the exception of the SHEP study. People who reach a very old age share some characteristics which make them different from the bulk of "60 (or 65) and over" and justify special studies which are currently in progress. In the meantime, any treatment decision can only rely on extrapolations moderated by common sense.

Ideomotor apraxia test: a new test of imitation of gestures for elderly people.

Ideomotor apraxia is one of the earliest disturbances in Alzheimer's disease (AD); no test of this disturbance has yet been validated for elderly people. We propose a test of meaningless gesture imitation and its relevance in elderly people is studied. The Ideomotor Apraxia Test (IAT) consists of showing 10 gestures. Each item is graded from 0 to 3. IAT was carried out on 55 patients with AD (mean age: 86.8 +/- 6.8 (71-100); mean MMS score: 14.6 +/- 6.3) and 26 elderly patients without cognitive impairment (mean age: 84.1 +/- 7.5 (70-100); mean MMS score: 27.5 +/- 1.9). The inter-rater reliability, a threshold, the apparent sensitivity and specificity and the relationship between the MMS score and the ideomotor apraxia score were determined. The mean apraxia score was 14.9 +/- 7.3 in the AD group and 28 +/- 1.6 in the normal group (P < 0.0001). Inter-rater agreement is excellent (P = 0.995). The threshold is 27. The apparent sensitivity and specificity are very good (95% and 88%, respectively). The correlation between the MMS score and ideomotor apraxia score is excellent (r = 0.83 (95% CI; 0.72-0.91). Age and educational level do not influence ideomotor apraxia score. IAT is the first test that evaluates meaningless gesture imitating capacity in an elderly population. It is an easy and quick-to-perform test, useful routinely for diagnosis of AD. It could contribute to the early diagnosis of AD and is correlated with the severity of cognitive impairment. Copyright 1998 Lippincott Williams & Wilkins