Cerebrovascular Disease Pathology and Parkinsonian Signs in Old Age

Background and Purpose—Mild motor symptoms including parkinsonian signs are common in old age, but their underlying neuropathology is unclear. We tested the hypothesis that cerebrovascular pathologies are related to parkinsonian signs.

Methods—We studied brain autopsies from 418 deceased participants from the Religious Order Study, who underwent evaluation of parkinsonian signs with a modified version of the motor section of the Unified Parkinson's Disease Rating Scale. Brains were evaluated for macroscopic and microinfarcts and the severity of arteriolosclerosis. Regression analyses were used to examine the association of cerebrovascular pathologies with parkinsonian signs.

Results—More than 35% of cases (N=149) showed macroscopic infarcts. Almost 30% of cases without macroscopic infarcts showed pathologies not detected by conventional brain imaging: microinfarcts (N=33 [7.9%]), arteriolosclerosis (N=62 [14.8%]), or both (N=24 [5.7%]). Macroscopic infarcts, specifically multiple cortical and ≥1 subcortical macroscopic infarcts, were related to higher global parkinsonian scores. The presence of multiple and cortical microinfarcts was associated with global parkinsonian score. Arteriolosclerosis was associated with global parkinsonian score, but this effect was attenuated and no longer significant after accounting for infarcts. Each of the 3 pathologies was separately associated with parkinsonian gait (macroscopic infarcts [estimate, 0.552; SE, 0.210; P=0.009]; microinfarcts [estimate, 0.424; SE, 0.213; P=0.047]; arteriolosclerosis [estimate, 0.191; SE, 0.056; P<0.001]). Further analyses showed that subcortical macroscopic and microinfarcts were specifically associated with the severity of parkinsonian gait.

Conclusions—Cerebrovascular pathologies, including macroscopic infarcts, microinfarcts, and arteriolosclerosis, are common in older persons and may be unrecognized common etiologies of mild parkinsonian signs, especially parkinsonian gait, in old age.

From press release:

Many common signs of aging, such as shaking hands, stooped posture and walking slower, may be due to tiny blocked vessels in the brain that can't be detected by current technology.

In a study reported in Stroke: Journal of the American Heart Association, researchers examined brain autopsies of older people and found:

•Microscopic lesions or infarcts -- too small to be detected using brain imaging -- were in 30 percent of the brains of people who had no diagnosed brain disease or stroke.
•Those who had the most trouble walking had multiple brain lesions.
•Two-thirds of the people had at least one blood vessel abnormality, suggesting a possible link between the blocked vessels and the familiar signs of aging.
"This is very surprising," said Aron S. Buchman, M.D., lead author of the study and associate professor of neurological sciences at Rush University Medical Center in Chicago. "There is a very big public health consequence because we're not capturing this 30 percent who have undiagnosed small vessel disease that is not picked up by current technology. How would you even get them on your radar? We need additional tools in our toolkit."

In 1994, the researchers began conducting annual exams of 1,100 older nuns and priests for signs of aging. The participants also donated their brains for examination after death. This study provides results on the first 418 brain autopsies (61 percent women, average 88 years old at death).

Although Parkinson's disease occurs in only 5 percent of older people, at least half of people 85 and older have mild symptoms associated with the disease.

Before the study, researchers believed that something more common, such as microscopic blocked vessels, might be causing the physical decline. The study's autopsies found the small lesions could only be seen under a microscope after participants died.

The lesions couldn't be detected by current scans.

During the annual exams of the nuns and priests, researchers used the motor skills portion of a Parkinson's disease survey to assess their physical abilities. Researchers observed and rated the participants':

•Balance
•Ability to maintain posture
•Walking speed
•Ability to get in and out of chairs
•Ability to make turns when walking
•Sense of dizziness
"Often the mild motor symptoms are considered an expected part of aging," said Buchman, who is also a member of the Rush Alzheimer's Disease Center. "We shouldn't accept this as normal aging. We should try to fix it and understand it.

If there is an underlying cause, we can intervene and perhaps lessen the impact."