[Practical approach of insomnia in the elderly]. / Approche pratique de l'insomnie en geriatrie: de la plainte au traitement.

Elderly people often suffer from insomnia which is responsible for high comorbidity and lower quality of life in this population. Somatic and psychiatric pathologies must be screened as primary sleep disorders. Chronic sleep disorders and benzodiazepine abuse might be avoided by an early treatment of causal factors. We wished to propose here a practical approach of the insomnia in the elderly going from the diagnosis to the treatment by advancing the not pharmacological approaches, while specifying at best the place of different drugs available and their limits.

Adverse Drug Reactions Due to Opioid Use in Oldest-Old Patients Visiting the Emergency Unit of the Geneva Geriatric Hospital.

Opioid use has much increased in several countries during the last two decades, accompanied by a rise in associated morbidity and mortality, especially in the United States. Data on a possible opioid crisis are scarcer in Europe. We performed a study aiming to assess the frequency of adverse drug reactions (ADR) related to opioids in patients presenting to the emergency unit (EU) of a geriatric tertiary Swiss University Hospital. This particular setting is intended for patients aged 75 and older. Our retrospective, monocentric survey of opioid use and related ADR was conducted over two months in 2018. The main and secondary outcomes were the frequency of EU visits considered due to an opioid ADR and insufficient pain relief, respectively. Current opioid use was identified in 20.3% (n=99) of the 487 included EU visits (mean age 86). An ADR was the suspected cause of the EU visit in 22 opioid users, mainly fall-related injury and gastrointestinal disorders. All these patients had at least one comorbid condition. In 19/22 cases (86%) of ADR, a drug-drug interaction might have been involved. In 12 opioid users (12%), insufficient pain relief was suspected as the cause of the EU visit. In conclusion, one-third of opioid users visiting a geriatric EU consulted for a problem related to its use mainly adverse drug-related reaction (22%) followed by insufficient pain relief (12%).

[Interference of brain reserve on cognitive disorders]. / Rôle de la réserve cérébrale en pathologie cognitive.

The "Brain Reserve" hypothesis was raised after the analysis of the results of the first longitudinal surveys comparing in nuns the neuropsychological aging process and the post mortem brain pathological findings. Numerous discordances were discovered: a) Persons with high education, high IQ and complex working responsibilities could benefit of a healthy cognition until death while their neuro-pathological brain findings were concordant with the International pathological criteria of Alzheimer disease and b) Moreover the same persons with a high brain reserve suffering from Alzheimer Disease have late, atypical symptoms and signs of the disease explaining a delayed diagnosis. In these patients the progress of the disease is always quick and severe.

[Delirium in old age. Difficulties in diagnosis]. / Syndrome confusionnel du sujet âgé: les difficultés d'un diagnostic facile.

Confusion is a frequent psychiatric and behavioural manifestation of diffuse cerebral injury found in elderly patients that are severely ill or stressed. The hyperactive form is often recognised because of the psychomotor agitation. However, the hypoactive form is most frequent and has a worse prognosis. Despite, it is often under-recognised. Among contributing factors, anticholinergic agents and drug interactions are significant. Identification and treatment of the underlying cause of delirium is essential with a focus on non pharmacological approach. Antipsychotic agents are reserved for severe forms and where non pharmacological intervention fracases.

Malnutrition in Very Old Hospitalized Patients: A New Etiologic Factor of Anemia?

BACKGROUND: Anemia and malnutrition are highly prevalent, frequently concomitant and associated with negative outcomes and mortality in the elderly. OBJECTIVES: To evaluate the association between these two entities, and test the hypothesis that protein-energy deficit could be etiology of anemia. DESIGN: Prospective case-control study. SETTING: Geriatric and Rehabilitation Hospital, Geneva University Hospitals, Switzerland. PARTICIPANTS: 392 patients (mean age 84.8 years old, 68.6% female). MAIN OUTCOME MEASURES: Hematological (hemoglobin (Hb)), chemical (iron work up, cyanocobalamin, folates, renal function, C-Reactive Protein (CRP)) and nutrition (albumin, prealbumin) parameters, and mini nutritional assessment short form (MNA-SF). RESULTS: The prevalence of anemia (defined as Hb<120 g/l) was 39.3%. Anemic patients were more frequently malnourished or at risk of malnutrition according to the MNA-SF (p=0.047), with lower serum albumin (p <0.001) and prealbumin (p <0.001) levels. Thirty-eight percent of these patients had multiple causes and 14.3% had no cause found for anemia. Among the latter 90.9% of patients with unexplained anemia had albumin levels lower than 35g/l. After exclusion of iron,vitamin B12 and folic acid deficits, anemic patients had lower albumin (p<0.001) and prealbumin (p 0.007) levels. Albumin level explained 84.5% of the variance in anemia. In multivariate analysis albumin levels remain associated with Hb only in anemic patients, explaining 6.4% of Hb variance (adj R2) and 14.7% (adj R2) after excluding inflammatory parameters (CRP>10). CONCLUSIONS: Albumin levels are strongly associated with anemia in the elderly. Screening for undernutrition should be included in anemia assessment in those patients. Further prospective studies are warranted in order to explore the effect of protein and energy supplementation on hemoglobin level.

[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.

Diabetes, comorbidities and increased long-term mortality in older patients admitted for geriatric inpatient care.

AIMS: To study the specific impact of diabetes on long-term mortality in very old subjects with multiple comorbidities and functional disabilities. METHODS: The prevalence of vascular disorders, global comorbidity load (cumulative illness rating scale [CIRS]) and functional disabilities (activities of daily living [ADL] and Lawton's instrumental ADL [IADL] scores) were determined according to diabetes status in a cohort of 444 patients (mean age 85.3±6.7 years; 74.0% women) admitted to our geriatric service. Also, the specific impact of diabetes on 4-year mortality was analyzed using Cox proportional-hazards models. RESULTS: Diabetic patients had higher BMI scores (27.1±4.9 vs. 23.4±4.7 kg/m(2) in controls; P<0.001), and higher prevalences of hypertension (81.9% vs. 65.1%, respectively; P=0.003) and ischaemic heart disease (33.7% vs. 22.2%, respectively; P=0.033), but not of stroke and renal insufficiency. They also had more comorbidities (CIRS score excluding diabetes: 15.1±4.5 vs. 13.8±4.8, respectively; P=0.016) and functional disabilities. Diabetes was associated with mortality (HR: 1.42, 95% CI: 1.02-1.99; P=0.041) after adjusting for age, gender and BMI, and this persisted after adjusting for individual vascular comorbidities, but disappeared after adjusting for CIRS, ADL or IADL scores. CONCLUSION: Diabetes was associated with 4-year mortality after adjusting for the inverse relationship between mortality and BMI. This association was better accounted for by the global comorbidity load and functional disabilities than by the individual vascular comorbidities. These findings suggest that the active management of all--rather than selected--comorbidities is the key to improving the prognosis for older diabetic patients.

Telomere length, comorbidity, functional, nutritional and cognitive status as predictors of 5 years post hospital discharge survival in the oldest old.

BACKGROUND: Telomere length has been considered in many cross-sectional studies as a biomarker of aging. However the association between shorter telomeres with lower survival at advanced ages remains a controversial issue. This association could reflect the impact of other health conditions than a direct biological effect. OBJECTIVE: To test whether leukocyte telomere length is associated with 5-year survival beyond the impact of other risk factors of mortality like comorbidity, functional, nutritional and cognitive status. DESIGN: Prospective study. SETTING AND PARTICIPANTS: A population representative sample of 444 patients (mean age 85 years; 74% female) discharged from the acute geriatric hospital of Geneva University Hospitals (January-December 2004), since then 263 (59.2%) had died (December 2009). MEASUREMENTS: Telomere length in leukocytes by flow cytometry. RESULTS: In univariate model, telomere length at baseline and cognitive status were not significantly associated with mortality even when adjusting for age (R²=9.5%) and gender (R²=1.9%). The best prognostic predictor was the geriatric index of comorbidity (GIC) (R²=8.8%; HR=3.85) followed by more dependence in instrumental (R²=5.9%; HR=3.85) and based (R²=2.3%; HR=0.84) activities of daily living and lower albumin levels (R²=1.5%; HR=0.97). Obesity (BMI>30: R²=1.6%; HR=0.55) was significantly associated with a two-fold decrease in the risk of mortality compared to BMI between 20-25. When all independent variables were entered in a full multiple Cox regression model (R²=21.4%), the GIC was the strongest risk predictor followed by the nutritional and functional variables. CONCLUSION: Neither telomeres length nor the presence of dementia are predictors of survival whereas the weight of multiple comorbidity conditions, nutritional and functional impairment are significantly associated with 5-year mortality in the oldest old.

Progression of Alzheimer disease in Europe: data from the European ICTUS study.

The clinical progression of Alzheimer disease (AD) was studied in European subjects under treatment with AChE inhibitors (AChE-I) in relation to geographical location over a 2-years period. One thousand three hundred and six subjects from 11 European countries were clustered into 3 regions (North, South, West) and investigated with biannual follow-up over 2 years. Primary outcomes were cognitive, functional and behavioral measures. Caregiver burden, hospital admission and admission to nursing home were also recorded. Participant cognitive function declined non-linearly over time (MMSE: -1.5 pts/first year, -2.5 pts/second year; ADAScog: + 3.5 pts/first year, + 4.8 pts/second year), while the progression of behavioral disturbances (NPI scale) was linear. Neither scale showed regional differences, and progression of the disease was similar across Europe despite different health care systems. Functional decline (ADL, IADL) tended to progress more rapidly in Southern Europe (p=0.09), while progression of caregiver burden (Zarit Burden Interview) was most rapid in Northern Europe (5.6 pts/y, p=0.04). Incidences of hospital admission (10.44, 95%CI: 8.13-12.75, p < 0.001) and admission to nursing home (2.97, 95%CI: 1.83-4.11, p < 0.001) were lowest in Southern Europe. In general cognitive and functional decline was slower than in former cohorts. European geographical location reflecting differences in culture and in health care system does not impact on the progression of AD but does influence the management of AD subjects and caregiver burden.

Early markers of prolonged hospital stay in demented inpatients: a multicentre and prospective study.

BACKGROUND: Dementia is a serious, chronic, and costly public health problem. Prior studies have described dementia as increasing length of hospital stay, but so far no explanations have been proposed. METHODS: To identify early markers for prolonged hospital stay in demented elderly inpatients, 178 community-dwelling or institutionalized subjects aged 75+, hospitalized through an emergency department in 9 teaching hospitals in France, were analyzed. Prolonged hospital stays were defined according a limit adjusted for Diagnosis Related Group. All patients underwent a comprehensive geriatric assessment at admission. Logistic regression multifactorial mixed model was performed. Center effect was considered as a random effect. RESULTS: Of the 178 stays, 52 were prolonged. Most concerned community-dwelling patients (86%). Multifactor analysis demonstrated that demographic variables had no influence on the length of stay, while diagnosis of delirium (OR 2.31; 95% CI 1.77 - 2.91), walking difficulties (OR 1.94; 95% CI 1.62 - 2.43) and report by the informal caregiver of moderate or severe burden (OR 1.52; 95% CI 1.19 - 1.86) or low social quality-of-life score (OR 1.25; 95% CI 1.03 - 1.40), according to the Zarit's Burden Inventory short scale (12 items) and the Duke's Health Profile respectively, were identified as early markers for prolonged hospital stays. CONCLUSION: At the time of the rising incidence of cognitive disorders, these results suggest that preventive approaches might be possible. In a hospital setting as well as in a community-dwelling population, more specific, specialized and coordinated care, using the expertise of multiple disciplines appears as a probable effective measure to limit prolonged hospital stay. Such approaches require (i) clear patient-oriented goal definition, (ii) understanding and appreciation of roles among various health care and social disciplines and, (iii) cooperation between partners in patient's management. However, the cost- and health-effectiveness of such approaches should be evaluated.

Vascular dementia. Differential diagnosis and therapeutic issues.

Although it has long been felt that dementia may be due to atherosclerosis, the concept has recently evolved to include multiple pathophysiological mechanisms related to deficiencies in cerebral blood supply. Epidemiological data has identified hypertension and stroke as the most potent risk factors for the development of vascular dementia (VaD). New diagnostic criteria have been proposed and new neuroimaging techniques have led to a better detection of cerebral vascular pathology. However, the differential diagnosis between Alzheimer's disease and VaD, the two most common causes of dementia, remains clinically challenging. Therapeutic interventions for VaD are limited, nevertheless several lines of evidence suggest a strong potential for preventive treatment through the control of vascular risk factors.

Economic considerations of Alzheimer's disease and related disorders.

Economic analyses of geriatric syndromes are seldom performed. However, demographic and epidemiological imperatives have led to significant interest in the evaluation of AD-related costs. Over 300 papers devoted to economic considerations of Alzheimer's disease have been published in peer-reviewed journals, within the last five years. In these papers, the chosen perspective (costs to society or to specific payers) is important. Analytical methods are still evolving and remain complex. Unresolved methodological issues will need to be addressed to further our understanding of long-term economic consequences. At present, it is clear that diagnostic and drug costs are low compared to the major cost of institutionalization. Thus, directing efforts at early diagnosis and delaying nursing home placement are two key cost-containment interventions. In this respect, the need to support informal care should not be underestimated.