Alzheimer's Disease: Overview and Risk Factors

Alzheimer's disease is a slowly progressive dementia characterized by memory loss and behavioral changes. Pathological changes in the brain include atrophy of the cerebral cortex (particularly in the temporal and parietal lobes), the presence of neurofibrillary tangles and senile (amyloid) plaques, a loss of cholinergic neurons in the brain, and reduced activity of choline acetyltransferase (the enzyme responsible for acetylcholine production) in the cerebral cortex and hippocampus. The presence of the allele ApoE epsilon 4 (e4) is a major risk factor for Alzheimer's disease, as it is associated with increased amyloid plaque accumulation.

The disease progresses from mild memory impairment to severe cognitive loss with personality/behavioral changes, sometimes including irritability, delusions and hallucinations. Often there are language problems (particularly with generation of nouns (dysnomia)), and spatial disorientation is common. Alzheimer's disease reduces life expectancy by as much as 50% following initial diagnosis.¹

Risk Factors

Alzheimer's disproportionately affects women and African Americans. Evidence suggests that Alzheimer's disease is associated with the following:

• Older age. Results of a U.S. community study (n=3,623) estimated prevalence at 3.0% for ages 65 to 74, 18.7% for ages 75 to 84, and 47.2% for those over 85.2 In 2000, 4.5 million people in the United States had Alzheimer's, and that number will nearly triple by 2050 with the aging of the population.³
• Family history. Risk is inversely proportional to the age of onset in a first-degree relative.
• Genetics. Presence of the ApoE e4 allele and other genetic factors such as trisomy 21.⁴
• Insulin resistance.⁵
• Hypercholesterolemia.⁴ Of the 1,037 postmenopausal women enrolled in the Heart and Estrogen/Progestin Replacement Study, those with LDL cholesterol levels in the top 25 percent had 76% greater odds of developing cognitive impairment, compared with women who had lower LDL levels.⁶
• Overweight. Women over the age of 70 had a 36% increased risk for Alzheimer's disease for every one point increase in body mass index.⁷ This finding has not been replicated in men.
• Hypertension,⁴ declining blood pressure over time, cerebro/cardiovascular disease, diabetes, smoking, and persistently elevated alcohol use. All of these factors are associated with cerebral atrophy. Being overweight may exacerbate these factors or lead to cerebral atrophy directly.⁸
• Elevated homocysteine.^9,10