Common Signs of Aging Traced to Tiny Brain Blockages

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By John Gever, Senior Editor, MedPage Today


Blocked blood vessels in the brain, often too small to be seen with current medical imaging technologies, may explain some of the common signs of aging such as diminished walking ability and hand tremors, researchers said.


Brain autopsy findings showed microscopic infarcts in 57 individuals out of 418 examined, the presence of which was significantly associated with gait abnormalities similar to those seen in Parkinson's disease, reported Aron S. Buchman, MD, of Rush University in Chicago, and colleagues.
Signs of arteriolosclerosis invisible with standard imaging were also significantly associated witparkinsonian gait, as were macroscopic infarcts that would be picked up with CT or MRI scans, the researchers indicated online in Stroke: Journal of the American Heart Association.

"We are not aware of previous studies demonstrating independent roles for microinfarcts and the severity of arteriolosclerosis in the development of parkinsonian gait," Buchman and colleagues wrote.

"Given that microinfarcts and severity of arteriolosclerosis are not discernible during life, these pathologies likely represent unrecognized common etiologies for parkinsonian gait in older persons and support clinical-imaging studies that suggest subclinical cerebrovascular disease abnormalities are associated with gait dysfunction in older persons."

The researchers added that more aggressive prevention and treatment strategies for vascular risk factors "might decrease the burden of mild age-related parkinsonian signs."

Such symptoms, which include rigidity and sluggish movements as well as tremors and gait problems -- are common in the elderly, affecting up to half of noninstitutionalized people 85 and older, according to Buchman and colleagues.

They pointed out that, although these symptoms are shared with Parkinson's disease (hence the "parkinsonian" rubric), most individuals showing them do not have the disease, as Lewy bodies and nigral degeneration, its neurological hallmarks, are absent.

On the other hand, cerebrovascular defects are common in older people and are known to produce parkinsonian symptoms, the researchers indicated.

To explore the connection, they reviewed autopsy findings from 418 deceased participants in the Rush Religous Orders Study, a prospective study that began in 1993 involving some 1,100 older nuns, brothers, and priests who underwent annual physical and psychological exams.

Those included in the current analysis had no signs of dementia at enrollment. At death, they averaged 88.5 years old and about 60% were women. Mean scores on the Mini-Mental State Examination at their last visit were 22.7, indicating significant cognitive impairment.

Microscopic infarcts were present without other abnormalities in 7.9%, and accompanied by arteriolosclerosis not detected in brain scans in 5.7%.

These small arteriolosclerosis lesions were seen alone in 14.8% of the autopsied brains, and relatively large infarcts were found in 36%.

At their yearly evaluations, study enrollees were assessed for Parkinsonian symptoms using a 26-item instrument derived from the Unified Parkinson's Disease Rating Scale. Each of the four major symptoms -- abnormal gait, bradykinesia, tremor, and rigidity -- were evaluated on 100-point scales. The average of these scores served as a global summary.

At death, the 418 individuals had had the following mean scores at their last evaluation:

•Gait: 41.5

•Rigidity: 11.7

•Bradykinesia: 21.4

•Tremor: 5.2

•Global summary: 18.6

Macroscopic infarcts were the most powerful predictors of these symptoms. Their presence was associated with increases of 0.359 points in the global score (P=0.013), 0.552 points on the gait scale (P=0.009), and 0.853 points on the rigidity scale (P<0.001).

Infarcts too small to be seen on imaging were associated with a 0.424-point increase in gait scores (P=0.047).

Arteriolosclerosis was a much smaller factor, although its association with gait scores (0.191 points, P<0.001) was statistically significant.

The location of infarcts within the brain appeared partly to determine their impact on parkinsonian signs. Multiple subcortical microinfarcts were more strongly associated with impaired gait (0.888 points, P=0.004) than cortical microinfarcts, the researchers found.

Similarly, subcortical macroscopic infarcts were also apparently more damaging than those within the cortex.

"Together these data suggest that a substantial portion of older people have brain tissue damage and small vessel disease that are unlikely to be detected before death and suggest that cerebrovascular disease may be an even larger public health challenge than currently estimated," Buchman and colleagues wrote.

They cited some limitations to the study. Microinfarcts and small arteriolosclerosis lesions were counted only in certain brain regions, potentially underestimating the association with parkinsonian signs. Study participants did not undergo brain imaging, so it is possible that signs of the cerebrovascular defects could be discernible in some cases.

Finally, the cross-sectional study design precludes firm conclusions about the direction of causality.

"It is possible that the cerebrovascular pathologies do not play a causal role in the development of parkinsonian signs, but rather both cerebrovascular pathologies and parkinsonian signs might be caused by a third factor," Buchman and colleagues noted.

The analysis was supported by the National Institutes of Health and the Illinois Department of Public Health.

Study authors declared they had no relevant financial interests.

Primary source: Stroke

Source reference:

Buchman A, et al "Cerebrovascular disease pathology and parkinsonian signs in old age" Stroke 2011; DOI: 10.1161/STROKEAHA.111.623462.