Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer’s disease? (original) (raw)

Primary Prevention of Alzheimer’s Disease (AD)

Geriatric Medicine and Gerontology, 2019

Alzheimer dementia (AD) is a complex, aging-associated disease whose effects on the brain (an organ made up by nonreplaceable cells) are devastating. Disease is not curable, but progress in pathobiology shows that intervention on aging can make primary prevention of AD feasible. According to the amyloid-cascade hypothesis, mechanisms of AD include: an age-related alteration of free radical metabolism in membranes, leading to a higher yield in the toxic Aβ1-42 peptide and an overwhelming impact on the weaker repair mechanisms of the aging cells. The proposed intervention on aging with anti-AD effects includes a daily assumption of antioxidants (red wine polyphenols enriched with resveratrol), a reinforcement of membrane antioxidant defenses by the assumption of polyunsaturated fatty acids at the first meal after fasting, and an enhancement of cell repair function (at the proteasome and autophagy level by an intermittent feeding regimen and physical exercise plus the assumption of antilipolytic agents during time of fasting). The beneficial effects of diet and physical activity on the endogenous production of protective nerve growth factors are magnified by an enriched environment. Treatment has already been started on healthy individuals at a higher risk of AD in the city of Volterra.

Alzheimer disease: are we intervening too late

The affirmative position is argued in response to the question of whether intervention in the disease course of Alzheimer disease (AD) occurs too late. AD is not a singular, homogeneous disease, but rather a final common pathway or end-point that can be arrived at through multiple routes. As part of the affirmative argument , there is a delineation of two long-term trajectories leading to AD: (1) normal elderly progression to AD, and (2) depressed elderly progression to AD. In documenting normal elderly devolution into AD, two ''normal'' elderly pre-AD or prodromal stages are discussed: age-associated memory impairment (AAMI) and mild cognitive impairment (MCI). Data are provided evidencing significantly high conversion rates from these pre-AD stages to actual AD. Using the same paradigmatic approach that is used in documenting normal elderly decline into AAMI and MCI with eventual conversion to AD; there is explication of depressed elderly conversion to AD. The long-term, mul-tiphasic disease progression of major depression without dementia to depressive dementia to final conversion to AD is brought into focus as another example of why intervention must occur prior to actual conversion to AD. Depression is defined as a cognitive syndrome and risk factor for AD requiring aggressive targeted intervention. AD does not just come suddenly out of nowhere. First intervention must occur during the pre-AD phases in an attempt to prevent, delay, and interrupt long-term neuro-degenerative processes involved in both normal elderly and depressed elderly conversion to AD. A primary strategy proposed is to delay onset of AD. Population statistics indicate that if AD is delayed by a modest 1 year, there would be 9.5 million fewer cases by 2050, resulting in significant reduction in burden of disease. Data show early intervention with cognitive stimulation (mental exercise), physical exercise, aggressive treatment of AD risk factors and excess disability, psychotherapy, and other nonphar-macological interventions in combination with each other and/or with medications can result in delay of onset of AD. First intervention at time of diagnosis of AD is too late, when by definition, final conversion to AD has already occurred. When we have knowledge to successfully intervene earlier, why would we not want to do so.

Preventing Alzheimer’s: Our Most Urgent Health Care Priority

American Journal of Lifestyle Medicine, 2019

Dementia is the fastest growing epidemic in the developed nations, and if not curtailed, it will single handedly collapse our health care system. The prevalence of dementia is 1 in 10 individuals older than 65 years and increases to 50% of all individuals older than 85 years. The prevalence of Alzheimer’s dementia (AD), the most common form of dementia, has been increasing rapidly and is projected to reach 16 million individuals by the year 2050. Several prevailing myths about the science of dementia are discussed, such as that AD is inevitable and that it is exclusively a genetic disease. The fact is that AD is dependent on a multitude of genetic, epigenetic, and environmental factors that interact with one another. In fact, 4 core drivers represent 90% of what determines disease progression in AD. These are (1) glucose or energy dysregulation, (2) lipid dysregulation, (3) inflammation, and (4) oxidation. Lifestyle change can significantly alter the course of AD. The authors have c...

Alzheimer’s Disease: Our Evolving View, Our New Interventions

Delaware Journal of Public Health

Alzheimer's Disease (AD) looms over our aging population like no other health problem. Its soaring prevalence, high cost of care, and lack of a curative treatment threaten our entire health care system, which struggles to address the needs of an estimated 5.4 million affected Americans and their caregivers. This year alone, nearly half a million Americans age 65 or older will develop AD. By mid-century, someone in the U.S. will develop the disease every 33 seconds. Delaware, as a favored retirement destination, is home to some 26,000 people with AD or a related disorder, and this number will increase substantially in coming years. 1 Barring the development of medical breakthroughs to prevent, slow, or stop the disease by 2050, the number of people age 65 and older with AD may nearly triple by then.

Primary prevention and delay of onset of AD/dementia

There are approximately 350,000 Canadians estimated to be suffering from dementia today, the majority (65%) from Alzheimer's disease (AD). The incidence rate of dementia in Canada is estimated at 20.6 new cases per 1,000 per annum. With the projected growth of the senior population, the number of affected individuals is predicted to increase to over a million in the next three decades. 1 The associated costs of dementia are incalculable for the patients and their families, and are anticipated to be staggering for Canada's health system. In 1991 a conservative health-economic study from the Canadian Study of Health and Aging (CSHA) estimated the cost of care at $3.9 ABSTRACT: Prevention in Alzheimer's disease and other dementias (AD/dementia) is defined on the basis of clinical states and their expressed symptoms. Primary prevention refers to delaying the development of the full-blown state of clinically expressed disease in normal individuals. Current primary prevention research is driven by evidence of AD/dementia protective factors that have emerged from epidemiological studies. The first randomized controlled trials (RCTs) of primary AD/dementia prevention have been designed to test the efficacy and safety of NSAIDs, hormonal therapy, antihypertensive drugs and antioxidants. The experience of these trials has indicated safety concerns as a key issue and highlighted significant design challenges in this type of research. These trials have required large sample sizes and unsustainable costs. There should be consideration given in future trials to enriching study samples with risk factors to increase progression rates to AD/dementia. Innovative strategies will also be needed to recruit and retain subjects given the long follow-up periods, modest perceived benefit and the potential for the risk-benefit ratio to change during the trial. It is foreseeable that regulatory authorities will be presented with primary prevention RCTs for approval and labelling, and that criteria to evaluate such evidence still need to be developed. RÉSUMÉ: Prévenir et retarder l'apparition de la MA/démence. La prévention de la maladie d'Alzheimer (MA) et des autres démences (MA/démence) se définit sur des bases cliniques et symptomatiques. En prévention primaire, on cherche à retarder l'apparition de la maladie avérée au point de vue clinique chez des individus normaux. Actuellement, la recherche en prévention primaire est basée sur des données provenant d'études épidémiologiques sur les facteurs de protection contre la MA/démence. Les premiers essais contrôlés randomisés (ECRs) en prévention primaire sur la MA/démence ont été conçus pour évaluer l'efficacité et la sécurité d'AINSs, de traitements hormonaux, d'antihypertenseurs et d'antioxydants. L'expérience acquise au cours de ces études a soulevé des questions importantes concernant la sécurité et a fait ressortir des défis importants quant au plan de ce type de recherche. Ces essais nécessitent de très grands échantillons et entraînent des coûts prohibitifs. À l'avenir, on devrait considérer enrichir les groupes en incluant des sujets ayant des facteurs de risque afin d'augmenter le taux de progression à la MA/démence. Des stratégies novatrices seront également nécessaires pour recruter et maintenir la participation des sujets aux études étant donné le suivi à long terme, les bénéfices perçus comme étant modestes et le taux de risques/bénéfices qui peut changer pendant l'étude. Il est à prévoir que des ECRs en prévention primaire seront présentés aux organismes de régulation pour approbation et étiquetage du conditionnement des médicaments et que des critères d'évaluation des données ainsi générées devront être développés.

NATURE AGING Next generation AD patient journey 2022

D is a chronic, nonlinearly progressive, multifactorial neurodegenerative disease that affects multiple domains of an affected individual's life during advanced stage of progression, such as cognition, behavior, functional abilities and social interactions. AD is the most common cause of dementia, accounting for around 60-80% of cases 1. In 2019, over 50 million people were living with dementia worldwide, and the number is expected to rise to 152 million by 2050, largely driven by the projected increases in low-income and middle-income countries 2. With population growth and aging, AD is becoming one of the most burdensome and costly diseases facing global society today 3. Historically, the diagnosis and treatment of AD focused on clinical symptoms. In the past three decades, in vivo biomarker studies identified core pathophysiological alterations-including amyloid and tau-that characterize and underly AD across its decades-long preclinical and prodromal phases. Such evidence has transformed the disease concept from clinically defined to biologically defined (Box 1) 4,5. This transformation opened the gate to biomarkerguided, molecular pathway-based targeted therapies 6,7. To date, a new wave of pharmacological compounds targeting AD pathophysiological hallmarks have reached late-stage clinical development with one agent recently approved by the US Food and Drug Administration (FDA) for clinical use in treating AD 8-12 .

Prevention of age-associated dementia

Brain Research Bulletin, 2009

The advancement of medical sciences during the last century has resulted in a considerable increase in life expectancy. As more people live to old age, one of the most fundamental questions of the 21st century is whether the number of individuals suffering from dementia will also continue to increase. Alzheimer's disease (AD) accounts for the majority of cases of dementia in the elderly, but there is currently no curative treatment available. Several strategies have been introduced for treatment, the most recent strategy of which was the immunization of patients using antibodies against A␤, which is a naturally occurring, even though misfolded peptide in the AD brain. Both active and passive immunization routes have been shown to reduce the pathology associated with A␤ accumulation in brains of genetically designed animal models. However, despite tremendous efforts, no unequivocal proof of therapeutic efficacy could be shown in AD patients. Particularly, the persistence of the neurofibrillary tangles in immunized brains and the issue of inducing cerebral amyloid angiopathy are major limiting factors of antibody therapy. Furthermore, physical activity, a healthy immune system and nutritional habits are suggested to protect against the onset of age-associated dementia. Thus, accumulative evidence suggests that an early integrated strategy, combining pharmacological, immunological, nutritional and life-style factors, is the most pragmatic approach to delay the onset and progression of age-associated dementia.

Alzheimer disease update

Continuum (Minneapolis, Minn.), 2010

Alzheimer disease (AD) is a progressive neurodegenerative disorder affecting more than 37 million people worldwide and increasing in incidence based on its primary risk factor, advancing age. A growing body of knowledge regarding amyloid and tau neuropathology, genetic and environmental risk modifiers, early and atypical clinical presentations, and the use of symptom-modifying medical and psychosocial therapies is available to aid in the diagnosis and management of patients with AD. Exciting recent advances in neurobiology render the areas of genetic susceptibility, biomarkers for early disease detection and assessment of disease progression, and novel therapeutic strategies to modify the natural history of the disease compelling, but in need of further study before implementation into routine clinical practice is feasible.