Alzheimer's Disease Study

Trillion Dollar Problem
Due to our aging population and society’s difficulty managing these chronic diseases, America’s chronic disease population is projected to increase from today’s 133 million people to 157 million people in 2020; 81 million of these will have multiple chronic diseases.1 The current trajectory of chronic disease’s economic costs will swell from today’s $1.3 trillion to $6 trillion by 2050.2 The cost of Alzheimer’s, a disease with no effective cure or intervention to delay disease progression, could grow to over $1 trillion by 2050.3

The AD burden is compounded by the toll it takes on caregivers and the complexities involved in comorbidities. Alzheimer’s patients are highly likely to have multiple chronic conditions including hypertension, diabetes, congestive heart failure and dyslipidemia. Caregivers often suffer from health consequences and depression as a result of the constant stress involved in caring for their patients and loved ones. Although the primary aim of this study is to improve outcomes for Alzheimer’s patients, we also hope to ease the caregiver burden and advance the understanding of comorbidities in AD.

Exercise's Impact on Alzheimer's Disease
Physical inactivity is one of the most prominent risk factors for dementia including Parkinson’s and AD.4,5 Regular aerobic exercise has been shown to improve maximal oxygen uptake and increases the mean life span in animals and humans6-9 while inactivity has negative systemic effects on the body.10,11 Exercise has been shown to reduce the risk of numerous diseases including congestive heart disease,12,13 breast cancer,14 and colon cancer.15 There are many reasons to engage in physical activity, and evidence also suggests that a physically active lifestyle may help delay the onset of cognitive decline or even slow disease progression.

Physical activity and fitness may also reduce frequent complications such as injury from falls, mobility disability, and weight loss. Thus, raising overall physical fitness, in populations pre-disposed to AD or not, is highly likely to reduce the incidence of dementia or delay its onset. A delay in the onset of AD by just 5 years would reduce the expected prevalence of the disease by more than 1 million cases after 10 years, and by more than 4 million cases after 50 years.16

Neurotrophic Factors
While the mechanisms by which exercise may reduce AD risk are not fully understood, it is known that exercise involves the modulation of neurotrophins,17,18 oxidative stress,18 inflammation,19 amyloid-beta degradation enzymes,20,21 brain blow flow,22,23 and metabolism.24 Exercise-induced upregulation of neurotrophins involved in neurogenesis can improve memory and brain plasticity, increase resistance to stress and relieve depression. Exercise may even curb the generation of Aβ and enhance its degradation. Moderate to high intensity exercise results in increases in BDNF production,38 and mouse models of AD (AβPPswe) involved in 16 weeks of treadmill running had significantly decreased amyloid loads and higher BDNF levels.25

Figure 1. Potential vascular factors impacting risk of developing AD. From Middleton and Yaffe (2008).32

A graduated exercise regimen featuring aerobic exercise has also been shown to increase hippocampal volume and improve spatial memory. A 1-year exercise intervention increased hippocampal volume by 2%, which is equivalent to between a 1 and 2 year worth of age-related volume loss.6 exercise significantly increases healthy vascularization, cerebral blood flow and metabolism- all of which are impaired in AD (Figure 1).26-28 Vascular pathology is of particular concern, as its presence and degree of severity has been found to increase the risk and stage of AD at any level of AD neuropathologic findings.29 Patients with diabetes also have a higher risk of developing AD,30 and cholesterol is an important regulator of neuronal function that is hypothesized to modulate amyloid-plaque deposition in the brain.31 These abundantly positive effects of physical activity have both short- and long-term benefits for people at risk of or diagnosed with AD and dementia, and suggest a multifaceted strategy for targeting the disorder. That strategy need not be encapsulated in a pill or pharmaceutical, but may be undertaken simply, safely, and inexpensively with modifications in behavior.

Beneufit Innovation
Historically, the ability to predict, track, and manage disease progression has not been possible for AD patients, separating the sufferer from both the knowledge and ability to take control of their disease. Thus, despite a large body of evidence mentioned above suggesting that simple exercise routines can dramatically affect and even delay AD progression, patients have no framework within which to make use of these data or understand the potential impact in their lives. In particular, our approach would empower AD patients and caregivers with personalized exercise regimens, the knowledge and ability to track their symptoms (improvements or declines) and understand how to manage their disease successfully with easy-to-use software, on devices they or a family member likely already have.

Our study will produce a novel disease management platform (adFIT™) for mobile phone operating systems that will be informed by peer-reviewed research on how personalized, disease specific exercise may improve or delay AD symptoms. We will design the software to enable personalized coaching of exercise protocols proven to be effective AD interventions, such as walking and cardiovascular exercises, to reach a target heart rate tailored to the user based on age, sex, weight, and diagnosis. We will design the software to permit logging of exercise routines and cognitive (memory recall) tests, medication adherence, motivation, precise measurement of compliance to protocols, social engagement, and symptom tracking over time. Integration with modern sensor technology ensures the precise measurement of exercise performance and patient health. Our software will be intended to inform the patient, their physician, and their caregiving team in order to improve care, diagnosis, and quality of life. By leveraging technology that most people already have (smartphones and tablets), our solution has the potential to improve the lives of patients with AD. This affordable and scalable approach is novel and will empower the millions of people affected by AD, as well as potentially ease the over billions of dollars in annual costs of the disease to the US.

Our approach is innovative because it is low-risk, low-cost, widely applicable, widely available, non-exclusive of other treatments, requires minimal time commitment, empowers patients and caregivers, and builds upon technology within constant reach. Furthermore, our approach provides patients a tool to exert control over their disease progression and improve quality of life by becoming more physically fit. Finally, our tool will involve a large cohort for data analysis and will provide a new framework for treating a growing, aging population who are both technology savvy and interested in managing their disorder.

To find out more about this ground-breaking Alzheimer's study please contact us via phone or email.

Contact Info
Beneufit, Inc.
Phone: (415) 741-1660


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