Numerous studies conducted in recent years have suggested that most dementia—including cases correctly diagnosed as Alzheimer’s disease—probably traces not to a particular lesion type but to combinations of brain pathologies. A new study, said by its authors to be the largest and most comprehensive look at such data, strengthens the suspicion.

Lon White, MD, MPH, University of Hawaii, and colleagues reviewed autopsy results from hundreds of decedents who had participated in the Nun Study of Aging and Alzheimer’s Disease or the Honolulu-Asia Aging Study.

Their report ran in the March 15 edition of Neurology.

The team drew data from the cases of 334 Catholic nuns (average age at death, 90) and 774 Japanese-American men (average age at death, 88).

White et al. documented predictable rates of five different brain pathologies with known associations with dementia: Alzheimer’s, Lewy bodies, hippocampal sclerosis, microinfarcts and low brain weight.

There were signs of Alzheimer’s in close to half of the brains. However, only half of these had Alzheimer’s as the main lesion type.

Meanwhile, more than 75 percent of 279 participants who had severe Alzheimer’s pathology had at least one other type of lesion as well.  

The team further noted that most participants who, in their final years, had exhibited pronounced cognitive impairment had few or no Alzheimer’s-type brain abnormalities.

“Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only Alzheimer’s disease,” the authors write in their conclusion. “These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life.”

In a press release from the U.S. Department of Veterans Affairs, with which White is affiliated through the Pacific Health Research and Education Institute, White says there may be a positive upshot in the findings.

“The good news is that preventing any [of the pathologies] will be of benefit to the process of aging-related cognitive decline,” he says. “We can prevent illnesses currently diagnosed as Alzheimer’s disease by preventing any of the other four lesion types, even if we cannot directly prevent the Alzheimer’s lesions.”

As an example, White says physicians might more actively encourage patients to ward off high blood pressure, which has been linked to various types of lesion occurring in the brains of the elderly.