Lifestyle Intervention and Alzheimer’s Disease

Alzheimer’s disease (AD), the most prevalent type of dementia, represents the fastest-growing epidemic both in the United States and globally.

Currently, nearly 50 million individuals worldwide have been diagnosed with AD, and in the United States alone, there are more than 6.2 million who live with the diagnosis, with 1 new person diagnosed every 64 seconds.

Analysis projects an increase to 152 million diagnoses world-wide by 2050.

The emotional and financial costs of AD are staggering. In comparison, heart disease costs the US health-care system approximately $120 billion, while AD costs $355 billion in direct costs and another $257 billion in indirect costs.

Furthermore, these costs are expected to grow to more than $1.1 trillion in the next 20 years, significantly affecting the healthcare system.

Despite billions of dollars of investment over the last few decades for the treatment of AD, the US Food and Drug Administration (FDA) has approved only 1 drug — Aduhelm (aducanumab-avwa) — for disease course alteration.

Due to its minimal demonstrated benefits and potential adverse effects, its approval has been controversial.

Yet our under-standing of dementia etiology suggests that prevention or delay of onset of disease, through a comprehensive lifestyle intervention, may be a powerful option, as delaying symptoms by only 5 years may result in 41% fewer cases.

To date, our myopic approach to AD has hindered a detailed look into cognitive decline and lifestyle.9 Our focus has been on only 2 molecules, amyloid-beta (Aβ) peptide and hyperphosphorylated tau (p-tau), based on initial research demonstrating their role in the initiation and progression of disease.

Consequently, for the last few decades, the singular focus of research has been to block creation and accumulation of these proteins.

However, no drug targeting these proteins has demonstrated clinically meaningful results in AD treatment in clinical trials.

Yet there is plenty of research that implicates other factors in propagating or accelerating the disease process, including inflammation, oxidation, glucose dysregulation (insulin resistance/diabetes), lipid dysregulation, and direct toxic metabolic and traumatic processes.

Recognition of that has led to current interventional studies focusing on the effects of lifestyle intervention on individuals at risk of developing AD.