Alzheimer’s disease is present in about 1-2% of individuals beginning at age 65, and doubles in frequency every 5 years. Thus, by age 80, up to 40% of individuals may have Alzheimer’s disease. However, there are three specific circumstances where Alzheimer’s disease has an earlier age of onset.
Patients with Alzheimer’s disease with an age of onset under 65 can often have a family history reported to include a relative also affected by Alzheimer ’s disease. In most cases, this does not indicate that a specific gene mutation has been inherited as the cause of disease. A clinical diagnosis of Alzheimer’s disease is not necessarily the same as a pathological diagnosis of Alzheimer’s disease that shows microscopic plaques and tangles. This is because there are many causes of memory difficulty as we age. Indeed, only a small number of cases of Alzheimer’s disease are inherited by a single gene mutation on chromosomes 21, 1 or 14, and these individuals usually present in their third or fourth decade of life.
Another source of early-onset Alzheimer’s disease is Trisomy 21 or Down syndrome. Amyloid precursor protein is coded on chromosome 21. Individuals with Down syndrome have three copies of chromosome 21 and thus produce excess amyloid precursor protein which is converted to the form of amyloid that accumulates in the brains of individuals with Alzheimer’s disease.
The third source of early-onset Alzheimer’s disease involves individuals with sporadic Alzheimer’s disease that does not begin with memory difficulty. Collectively, this is sometimes referred to as the non-amnestic variant of Alzheimer’s disease. In these individuals, the presenting feature is difficulty with language, visuospatial functioning or executive control. The language disorder is called the logopenic variant of primary progressive aphasia; the visuospatial disorder is called posterior cortical atrophy; and the executive disorder is called the frontal variant of Alzheimer’s disease. Over time, these individuals can develop difficulty with memory and other cognitive domains, eventually resembling individuals with typical Alzheimer’s disease.