SAN FRANCISCO—Diabetes and parkinsonian-like signs are two chronic medical conditions that are common in the elderly. Both are associated with significant morbidity and mortality. Parkinsonian signs comprise a set of neurologic signs—such as stooped gait—that are progressive in old age. Diabetes is related to neurologic complications and is a risk factor for such prevalent diseases of aging as stroke, dementia, and Alzheimer’s disease. The two conditions have not been linked before; yet, could there be a connection?

According to the latest results of an ongoing clinical-pathologic study of aging, cognitive decline, and motor function loss, diabetes mellitus and parkinsonian syndrome are linked. Investigators at Rush University Medical Center in Chicago found that diabetes mellitus was significantly associated with worsening of two of the four parkinsonian signs for which patients were assessed: rigidity and gait disturbance. The association with rigidity held up even after investigators accounted for the presence of stroke; however, the presence of stroke reduced the association of diabetes with gait to a trend, suggesting that stroke accounts for at least part of this relationship. The presence of cardiovascular disease—namely, hypertension and myocardial infarction—did not modify the association of diabetes with either rigidity or gait.

The results suggest that diabetes mellitus may be a previously unrecognized risk factor for the progression of parkinsonian signs in older persons, said Zoe Arvanitakis, MD, from the Rush Alzheimer’s Disease Center at Rush University and principal investigator of the study.

“This study underlines the importance of recognizing that there is a relationship between these two common and disabling conditions,” she said. It might encourage clinicians to identify these conditions as early as possible, she added.

THE UNDERLYING MECHANISMS

Parkinsonian signs occur more frequently in the elderly than Parkinson’s disease, and the syndrome is differentiated from the disease by several different factors. The diagnosis of Parkinson’s disease is based on clinical findings made during the patient’s life, but the diagnosis cannot be absolutely confirmed until autopsy. During a lifetime, however, there are typically some cardinal clinical features that are shared by patients with Parkinson’s disease and those with parkinsonian syndrome, Dr. Arvanitakis explained.

“One important difference is that people with Parkinson’s disease respond to specific medications that treat this disease, whereas elderly persons with these more common parkinsonian signs don’t respond very well to those treatments,” she said. “They need to be treated with something different.”

Though parkinsonian syndrome has been recognized as a source of motor impairment and mortality in the elderly, few risk factors for these signs have been identified. It was this lack of understanding that provided the impetus for the study, according to Dr. Arvanitakis.

“What we were interested in was looking at this syndrome in elderly persons that is very common and yet doesn’t respond to treatment,” she said. “We don’t really understand what causes it. One approach to better understand parkinsonism in the elderly that isn’t Parkinson’s disease is to try to understand what risk factors might lead to that condition. We’re trying to eventually get at underlying mechanisms that lead to ... parkinsonian syndrome. If we understand that better, that may actually have a very important public health impact, because it’s such a common condition.”

Results were obtained in a cohort of more than 800 elderly Catholic priests, nuns, and brothers participating in the larger, ongoing Religious Orders Study, which is funded by the National Institute on Aging. Participants agreed to undergo an annual clinical evaluation, including a medical history, a neurologic examination, and cognitive testing, and they had to be without Parkinson’s disease or dementia at baseline. Patients were followed for an average of about six years.

Dr. Arvanitakis and her colleagues viewed the homogeneity of the cohort as a plus. “These are persons who have a very structured lifestyle and who have attained a very high education level and have characteristic occupations,” she observed. “The homogeneity of this group may represent a strength of the study. Further, all analyses were controlled for the potentially confounding factors of age, sex, and education.”

BRAIN PATHOLOGIES MAY PROVIDE FURTHER ANSWERS

Another benefit of studying this particular cohort is that all participants in the Religious Orders Study have agreed to brain donation at the time of death. To date, Dr. Arvanitakis and her colleagues have collected more than 200 brains of participants who have died in the course of the study. She is looking toward these and other clinical-pathological studies to help answer some remaining questions.

“We don’t know why diabetes appears to affect some parkinsonian signs—such as rigidity and gait in our study—while seemingly not affecting others” such as bradykinesia and tremor, Dr. Arvanitakis said. “We’d also like to examine which neurobiological mechanisms link diabetes to parkinsonian signs and which other common clinical disorders of old age—including, for example, dementia and cognitive impairment—might play a role in that relationship.”

This is one of the reasons why the investigators looked at stroke as part of the equation. Because diabetes mellitus is a risk factor for stroke and stroke, in turn, can contribute to loss of motor function, they considered the possibility that stroke might account for the relationship of diabetes to motor impairment. “The fact that the relationship with rigidity was clearly maintained and is still significant suggests that some central process is going on linking diabetes to disease of the central nervous system,” Dr. Arvanitakis said. “We need to better understand that, and hopefully pathologic studies will help clarify this question.”

She would also like to see further studies conducted to replicate these findings in a more diverse cohort. “Although homogeneity is an advantage for the reasons we discussed before, the flip side of the coin is that this particular cohort may not be representative of the general population,” she said.

Other types of studies, including clinical-radiological studies and those looking at the effect of diabetes on the brains of animal models, would also provide further insight into this relationship, Dr. Arvanitakis envisioned. “Once we understand the underlying mechanism whereby diabetes is linked to parkinsonian signs,” she concluded, “we’ll be in a better position to try to influence that relationship—in other words, manage or even prevent those parkinsonian signs that are deleterious.”

NR

—Fred Balzac

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