Dementia is an increasing problem and Alzheimer’s Disease (AD) is the most common form of dementia in
older adults, accounting for 60-80% of dementia cases. It is a leading cause of morbidity and mortality in
the aging population.

There are three interrelated hypotheses for the causes of AD including:

  1. Extracellular amyloid plaque formation due to increased production of amyloid beta42 in younger,
    genetically high-risk persons combined with reduced breakdown and removal among older persons
  2. Vascular disease that contributes to vascular dementia increased deposits of amyloid, and
  3. Aging causes neurodegenera5on independent of amyloid and vascular

Risk factors for Alzheimer disease include age (average age at diagnosis is 82 years with memory
concerns starting 16 years prior per the Rotterdam Study), family history of dementia (risk with a first-degree
relative with dementia is 10-30 percent), rare dominantly inherited gene mutations that impact
amyloid in the brain, the apolipoprotein E (APOE) epsilon 4 (e4)allele, and acquired risk factors.

Acquired risk factors include high blood pressure at midlife (age 45 to 65); abnormal lipids (cholesterol)
especially in mid-life and specifically with elevated total cholesterol or low-density lipoprotein
cholesterol (LDL); cerebrovascular disease associated with hypertension, diabetes, smoking, obesity, low
physical activity and hyperlipidemia; type 2 diabetes and obesity; poor lifestyle and low physical activity;
brain trauma with loss of consciousness of 30 plus minutes; medications including benzodiazepines,
anticholinergics, antihistamines, opioids, possibly proton pump inhibitors (malabsorption of B12 and
other nutrients long-term) with long-term exposure, and environmental risk factors including
secondhand smoke, air pollution, and pesticides.

To reduce the risk of AD, especially for people with early dementia and/or risk factors for dementia, we
recommend maintaining or increasing physical activity and exercise; increasing cognitive leisure activities
(memory training using external memory cues) and social interaction; treating hypertension, diabetes
and high cholesterol to reduce the risk of cerebrovascular disease, and consuming Mediterranean-style
diets that are high in fruits, vegetables, fish, nuts, and oils that have health benefits including reduced
cardiovascular risk. Vitamin E may have a modest benefit in slowing disease progression in patients with
mild to moderate AD, but is not recommended in otherwise healthy adults. There is some evidence that
Vitamin D deficiency is associated with cognitive impairment.

We all have much to learn about Alzheimer Disease but optimizing our health, especially between age
45 to 65 years of age, has the potential to delay or prevent a large number of dementia cases worldwide.