Prevention of Alzheimer's Disease and Cognitive Decline with Diet and Lifestyle: Proceedings of the A. G. Leventis Foundation Conference.

The A. G. Leventis Foundation International Conference, "Prevention of Alzheimer's Disease and Cognitive Decline with Diet and Lifestyle", was held on May 11-12th, 2022 in Nicosia, Cyprus. This conference examined the role of diet and lifestyle for the prevention and treatment of Alzheimer's Disease and other forms of cognitive decline. Speakers from leading academic institutions presented evidence on healthy dietary patterns, with a particular focus on the traditional Mediterranean diet (MedDiet), in association with cognitive outcomes, mainly cognitive decline, dementia, and Alzheimer's disease, from both observational and interventional studies. Moreover, future directions for the potential use of olive oil, rich in polyphenols, for its therapeutic use as a nutraceutical, as well as nutritional interventions with high-quality dietary patterns (i.e. MedDiet) that support existing primarily observational evidence for the prevention of cognitive decline, as well as challenges in designing rigorous clinical trials are summarized and discussed within the conference proceedings.

Frequency of Conditions Associated with Declines in Intrinsic Capacity According to a Screening Tool in the Context of Integrated Care for Older People.

BACKGROUND: The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. OBJECTIVES: To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). DESIGN: A cross-sectional retrospective analysis from the baseline assessment of the MAPT. SETTING: The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. PARTICIPANTS: Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. MEASUREMENTS: Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. RESULTS: Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. CONCLUSION: After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

Alzheimer's disease and related syndromes and hospitalization: a nationwide 5-year longitudinal study.

BACKGROUND AND PURPOSE: To study the association between Alzheimer's disease and related syndromes (ADRS) and the incidence of short-stay hospitalizations from the year before (Y-1 ) to 4 years after (Y1 -Y4 ) ADRS identification in the healthcare system. METHODS: Among all beneficiaries of the French health insurance general scheme aged 40 years or more, those with an incident ADRS in 2011, identified through long-term disease registry, hospitalization diagnoses or ADRS-specific drug delivery, were matched with beneficiaries without ADRS of the same age, gender and residence area. The annual incidence rates of all-cause hospitalizations (excluding those with a diagnosis code of ADRS) were compared between individuals with or without ADRS using incidence ratios (IRs) globally and by age, gender, deprivation index and modified Charlson score. We also studied cause-specific hospitalizations using patients' diagnoses and procedure codes. RESULTS: A total of 90 871 subjects with and 90 871 subjects without ADRS were included (mean age 79.6 years, 66% females). From Y-1 to Y4 , incidence rates were significantly higher in subjects with ADRS than in those without for all-cause hospitalization [IR(Y-1 ) = 1.73; 95% confidence intervals, 1.71-1.75; IR(Y4 ) = 1.37; 95% confidence intervals, 1.35-1.39], hospitalizations for social reasons [IR(Y-1 ) = 4.28; IR(Y4 ) = 2.70], fall [IR(Y-1 ) = 5.36; IR(Y4 ) = 2.59], injury [IR(Y-1 ) = 2.71; IR(Y4 ) = 2.09] and infection [IR(Y-1 ) = 2.04; IR(Y4 ) = 2.07]. The inverse was observed for hospitalizations for cataract surgery [IR(Y-1 )=0.73; IR(Y4 ) = 0.51] or total hip prosthesis after 2 years [IR(Y4 ) = 0.72]. CONCLUSIONS: Incident ADRS cases were associated with a higher incidence of hospitalization, but these subjects underwent some common non-emergency surgeries less frequently. Future studies need to assess the clinical impact of these differences.

Physical Activity and Changes in White Matter Hyperintensities over Three Years.

OBJECTIVES: Since physical activity (PA) has demonstrated benefits for cardiovascular health, it is possible to hypothesize that higher or increasing PA slows the progression of white matter hyperintensities (WMH). We investigated the association between PA and the progression of WMH in non-demented older adults with memory complaints. DESIGN: We included 152 participants (mean age 74.7±3.8 years; 63.8% women) in the analyses, in whom information on self-reported PA and MRI was available at both baseline and 3-year follow-up. From the PA questionnaire, the baseline metabolic equivalent of task (MET-minute/week) and changes in MET-minute/week over three years were separately calculated for overall, leisure-time, and non-leisure time PA. WMH volume at baseline and 3-year follow-up was obtained by using an automated segmentation algorithm. RESULTS: Mixed-effect linear regression models showed that none of the baseline PA variables was associated with progression of WMH over time. People who had decreased their PA levels over three years tended to show greater progression of WMH compared with those who had maintained PA levels of ≥1200 MET-min/week (roughly equivalent to ≥300 minutes of brisk walking) in the unadjusted model (ß±SE=4.85±2.42, p=0.045); however, this association was no longer significant after adjustment for confounders (ß±SE =3.63±2.18, p=0.096). CONCLUSIONS: We did not find any significant association between PA and WMH in non-demented older adults with memory complaints. However, decrease over time in PA levels tended to be associated with progression of WMH. A larger longitudinal study with data on PA assessed using objective measures would provide important information in this field.

Physical Activity and ß-Amyloid Brain Levels in Humans: A Systematic Review.

Physical activity (PA) contributes to brain health and plasticity, which suggests that PA would protect against the development of Alzheimer's disease (AD). However, research on PA and AD biomarkers is very scarce. The objective of the present study was to perform a systematic review of studies that investigated the associations between PA and ß-amyloid brain deposition in humans. Electronic searches were performed in PubMed, Cochrane Library, SportDiscus, PEDro, and PsychInfo databases. Articles were eligible if they have assessed both PA and ß-amyloid brain deposition in humans. Five articles, published between 2010 and 2013, met eligibility criteria (study population varied across studies from 54 to 515, according with the ß-amyloid measure. All five studies assessed both PA and PET-amyloid; among them, two studies also assessed CSF Aß42 levels). All studies were based on cross-sectional data, from non-demented populations. Among the five included studies, three found significant associations between PA and ß-amyloid brain deposition, and the other two did not find any significant association; limited evidence suggests that PA-amyloid plaques associations would be APOE ε4 allele-specific. In sum, no solid conclusions can be drawn on the associations between PA and human ß-amyloid brain deposition currently. Future research on this topic should particularly pay attention to the operationalisation of clinically relevant and valid PA variables and should include important confounders in multivariate analysis. More information is needed on the potential interactions between PA and other AD risk factors (e.g., cognitive activities, APOE ε4 status, nutrition, smoking) and their combined effects on AD biomarkers.

EU./U.S. CTAD Task Force on Alzheimer's Trial Populations.

Successful therapeutic trials require well-targeted populations to demonstrate the effectiveness of a drug candidate. Most trials in the field of Alzheimer's disease (AD) have been conducted in patients with mild to moderate dementia. However, the advent of amyloid PET imaging has demonstrated that a significant proportion of individuals enrolled in such studies do not have evidence of brain amyloidosis and may in fact not have Alzheimer's disease. Further, dementia represents an advanced stage of neurodegeneration, perhaps too late for significant benefits of disease-modifying interventions. The successful development of effective disease-slowing therapies requires a study population selected in accordance with the mechanism of the specific intervention. An international task force of investigators from academia, industry, non-profit foundations, and regulatory agencies met in San Diego, California, USA, on November 13, 2013, to address issues related to screening and identification of clinical trial participants, and the ramifications of decisions made in this regard for drug development in AD and other dementias.

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.

Predictive factors of hospitalizations in Alzheimer's disease: a two-year prospective study in 686 patients of the REAL.FR study.

BACKGROUND: During the course of the Alzheimer's disease (AD), many patients need to be hospitalized either due to the direct consequences of the disease itself, or due to associated diseases or life event. The objective of the present study was to determine predictive factors for hospitalisation in AD patients. METHODS: Six hundred eighty-six AD patients from the French Network on AD (REAL-FR) were follow up and assessed every 6 months for 2 years. During follow-up, all events occurring between two visits, in particular hospital admissions were carefully recorded. RESULTS: Annual incidences for hospitalizations were 26.13% (95% CI, 22.52 to 29.74). After two years, 202 subjects were hospitalized for 296 hospitalizations. Three variables were found to be significant predictors of hospitalisations in the multivariate regression model: dependency for ADL (RR=0.81; 95% CI: 0.70-0.95, p=0.0091), the drug use (use of four or more drugs) (RR=1.83; 95% CI: 1.31-2.58, p=0.0005) and the NPI score (RR=1.011; 95% CI: 1.001-1.022, p=0.0427). For hospitalizations due to the direct consequences of the disease itself, three variables were found to be significant predictors of hospitalisations: dependency for ADL (RR=0.69; 95% CI: 0.53-0.88, p=0.0033), the caregiver burden Zarit score (RR=1.03; 95% CI: 1.01-1.05, p=0.0079) and the NPI score (RR=1.07; 95% CI: 1.03-1.12, p=0.0007). CONCLUSIONS: Intervention to support patients and caregivers to manage loss of ADL may be a practical approach to reduce hospitalisation. Prevention of drug use or optimal treatment of associated diseases in AD seem to be also a challenge to decrease the rates of hospitalization or readmission, and the costs of providing care.

Nutritional assessment of residents in long-term care facilities (LTCFs): recommendations of the task force on nutrition and ageing of the IAGG European region and the IANA.

Unintentional weight loss and Undernutrition are major problems among older people living in Long-Term Care Facilities (LTCF). Undernutrition manifests in LTCF particularly as weight loss and low Body Mass Index (BMI) and is associated with increased morbidity and mortality as well as with functional decline. There are many factors associated with poor nutritional status and affecting protein-energy intake and/or energy expenditure. These include age of 85 years or older, low nutrient intake, loss of ability to eat independently, swallowing and chewing difficulties, becoming bed-ridden, pressure ulcers, history of hip fracture, dementia, depressive symptoms and suffering from two or more chronic illnesses. Nutritional evaluation is an essential part of the Comprehensive Geriatric Assessment (CGA). This evaluation ranges from methods such as BMI to several validated tools such as Mini-Nutritional Assessment (MNA). After diagnosis, the management of undernutrition in LTCF requires a multidisciplinary approach which may involve dietary and environmental improvements and managing multiple co-morbidities, while avoiding polypharmacy as far as possible. Finally, the need for supplementation or artificial (tube) feeding may be considered taking into account the CGA and individual needs. This document presents a succinct review and recommendations of evaluation and treatment of undernutrition.

Mild Alzheimer's disease: a "position paper".

Under the auspices of the Societe Francaise de Geriatrie et Gerontologie, a multi-disciplinary group of specialists in geriatrics, neurology, epidemiology, psychiatry, neuroradiology and nuclear medicine met with the aim of drawing up references on the methods for diagnosing and treating mild Alzheimer's disease. The critical analysis of international literature, conducted by Professor Bruno Vellas for the scientific committee, has served to support study of the latest knowledge in 2008. The multi-disciplinary group met on 14 and 15 May 2008 in order to set out the questions that this study must answer and to allocate draft studies. Thus, it has been possible to conduct a study focused on mild Alzheimer's disease, giving particular attention to diagnostic procedure, specific methods of treatment and the benefits of making a diagnosis.

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).

A nutritional education program could prevent weight loss and slow cognitive decline in Alzheimer's disease.

BACKGROUND: Weight loss is a common problem in patients with Alzheimer's Disease (AD). It is a predictive factor of mortality and it decreases patients' and caregivers' quality of life. OBJECTIVE: To determine if a nutritional education program can prevent weight loss in AD patients. SUBJECTS: 151 AD patients and their caregivers were enrolled to follow the intervention and 74 AD patients and their caregivers constituted a control group. METHOD: Caregivers in the intervention group followed 9 nutritional sessions of one hour each, over one year. Caregivers in the control group didn't follow any sessions but were offered advice provided in a normal follow-up. Patients weight, nutritional state, cognitive function, autonomy, mood, behaviour disorders at baseline and at 6- and 12-month follow-up. Caregivers burden, nutritional and AD knowledge at the baseline and at the 12-month follow-up. RESULTS: During the year follow-up, the mean weight increased in the intervention group (0.7+/-3.6 kg) whereas it decreased in the control group (-0.7+/-5.4 kg) (p<0.05). The nutritional status (MNA) was maintained in the intervention group (0.3+/-2.6) whereas it decreased significantly in the control group (-1.0+/-3.4) (p<0.005). After adjustment for baseline differences between the two groups (caregiver age, nutritional state, eating behaviour disorders, depression), the weight change between the two groups was not significant (0.6+/-0.4 kg vs. -0.6+/-0. 6 kg respectively in intervention group and control group). However, the percentage of patients with significant weight loss is decreased. The MMSE change became significant between the two groups: -2.3+/-0.3 vs. -3.4+/-0.4 respectively in intervention group and control group (p<0.05). CONCLUSIONS: These results suggest that a nutritional educational program intended for caregivers of AD patients could have a positive effect on patients weight and cognitive function.

[Diagnosis of cardiac tumor by percutaneous thromboaspiration. A case report]. / Diagnostic d'une tumeur cardiaque par thromboaspiration percutanée. A propos d'un cas.

Percutaneous endovascular thromboaspiration is a valuable tool as illustrated by the case of a patient suffering from a large intracardiac tumour. Histological and immuno-histochemical analysis of the tumour fragments provided the diagnosis of a cardiac angiosarcoma. The patient was a 44 year old man admitted for a large sero-sanguinous pericardial effusion which recurred after drainage. The case was complicated by a haemorrhagic cerebrovascular accident unrelated to a secondary deposit. Initially suspected after transthoracic echocardiography, the diagnosis of a tumour invading the right atrium was confirmed by transoesophageal echocardiography and cardiac CT scan. Surgery was declined and as the diagnosis of lymphoma could not be excluded, the patient underwent biopsy by an original method of percutaneous thromboaspiration. This minimally invasive, low cost technique would appear to be a valuable alternative to other endovascular biopsy techniques (saber, biotome) and to surgical biopsy, and could be proposed as the technique of first intent in an a priori non-operable intra-cardiac tumour or when lymphoma is suspected.

Alzheimer disease: protective factors.

Approximately 6-8% of all persons aged >65 y have Alzheimer disease and the prevalence of the disease is increasing. Any intervention strategy aimed at decreasing risks or delaying the onset of the disease will therefore have a substantial effect on health care costs. Nutrition seems to be one of the factors that may play a protective role in Alzheimer disease. Many studies suggest that oxidative stress and the accumulation of free radicals are involved in the pathophysiology of the disease. Several studies have shown the existence of a correlation between cognitive skills and the serum concentrations of folate, vitamin B-12, vitamin B-6, and, more recently, homocysteine. However, nutritional factors have to be studied not alone but with the other factors related to Alzheimer disease: genetics, estrogen, antiinflammatory drug use, and socioeconomic variables. The objective of this article was to review recent studies in this field.

Identification and purification of the specific antigen of Paracoccidioides brasiliensis responsible for immunoelectrophoretic band E.

A new purified antigen (E2) of Paracoccidioides brasiliensis mycelial growth phase was isolated by immunoadsorption from a crude metabolic soluble extract of the fungus. The antiserum prepared in a rabbit by inoculation of E2 antigen developed only one immunodiffusion line with the crude metabolic extract. Findings on immunological analysis showed that E2 antigen is the antigenic component of immunoelectrophoretic band E. The isolated antigens did not possess detectable alkaline phosphatase activity. It reacted in immunodiffusion tests with all the sera (14/14) from P. brasiliensis infected patients containing precipitating antibodies.

Sulphitolysis in keratinolysi. Biochemical proof.

The presence of S-sulphocysteine in filtrates of the dermatophyte Keratinomyces ajelloi growing on human hair in a culture medium buffered by pH 7-4 by phosphates was demonstrated by means of ion exchange chromatography techniques. S-sulphocysteine being destroyed during acidic hydrolysis was identified after enzymic hyrolysis of dialyzed and lyophilized filtrates. This result indicates that sulphitolysis occurs during kerationlysis performed by K. ajelloi. As thiosulphuric esters were shown present in hair perforations made by Microsporum gypseum, we think sulphitolysis is a common mechanism developed by dermatophytes to attack keratin.