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Alzheimer’s Disease: The Great Morbidity of the 21st Century

Neuroangiogenesis (NAG) provides a vascular basis for understanding Alzheimer’s disease, senile dementias and cognitive decline with aging

Charles T. Ambrose

Emergence Of Alzheimer’s Disease

In 1906 Alois Alzheimer (1864–1915) reported a single case study of a female with presenile dementia, whose brains showed a massive loss of neurons, gummy deposits and strongly staining fibrils. He later found the same histopathology in the brains of three other senile patients. These cases were first described in a 1910 text book on psychiatry, where the condition was given the eponym Alzheimer’s disease. But this name appeared only sparsely in the indexes of books on internal medicine before the 1950. Nor did these same texts include much about senile dementia, other than in association with neurosyphilis or schizophrenia. As a relevant aside, my father’s medical school text (Cecil and Kennedy, 1929) contained only two short sentences about Alzheimer’s disease (22 words), whereas my text (Cecil & Loeb, 1951) omitted AD entirely. The question arises whether before 1950 senile dementias (including AD) were so uncommon that they warranted little mention.

Gregory Zilboorg, a medical historian, reviewed the very old medical literature for reports of senile psychoses/dementia. Aretaeus of Cappadocia, a 2nd-century C.E. Greek in Rome, remarked that “mental decay is a calamity of old age—without intermittence and incurable.” Rhazes, a 9th–10th century Persian, viewed melancholy as inevitable “in the lives of old and decrepit persons.” Felix Platter, a 16th-century Swiss physician, observed that the memory of some elderly people is defective, especially for recent happenings. And Jean E. D. Esquirol (1772–1840) described the mental changes occurring with old age—a waning memory (especially of recent events), a shorter attention span, progressive fatigue, slower movements, irritability and unreasonableness.

If mental deterioration in the aged has been noted in the past but paid little attention in early 20th-century medical texts, what accounts for the recent clinical prominence of AD and its predicted great increase? Some suggest it is better recognition of late. But another explanation offered is that the current U.S. population is older than previous ones and thus has had more years for geriatric conditions to appear before death. This latter notion does not seem well supported by data comparing the Alzheimer’s death rate per 100,000 people (AD-DR) in countries with different life expectancies (LE) but comparable levels of diagnostic expertise. The United States has an LE of 75.6 years and an AD-DR of 24.6, whereas in Switzerland the LE is 79.3, but the AD-DR is only 20.0. Similarly, Finland has an LE of 75.9 and AD-DR of 34.9, whereas in nearby Sweden people live three years longer (78.9), but the AD-DR is only 21.9. Genetic differences among populations may dampen the effect of aging. In any case, research into other explanations seems warranted.

Indeed, investigators have searched for environmental factors to explain the apparent increased incidence of AD after World War II—aluminum in cooking vessels, atmospheric pollutants and so forth. But none has proved to be a convincing inciting cause. Based on the apparent recent rising incidence of AD, a putative contributing factor may have appeared around the mid-1950s and prevailed since. Radio executives and some educators might like to incriminate the stultifying effect of TV, while classic music lovers might blame the brain-deadening effect of raucous rock music, but I’m not persuaded. Recently epidemiologists have invoked “risk factors” (biomarkers) contributing to the development of AD—for example, obesity, diabetes, hypertension, head injuries, lower intelligence, less formal education, inactivity (both physical and mental), certain alleles and so on. The search for the etiopathology of AD over the past several decades has produced an enormous number of studies, of which only a very small fraction has been included in the following brief review.

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