Brain Abnormality Found In Alzheimer’s Disease Related to Gait Impairment in Older Persons

Results Suggest Alzheimer’s Disease May Be More Common than Previously Recognized

A new study from Rush University MedicalCenter helps explain why gait problems are often progressive in old age and related to risk of dementia and death.

The study, published in the January issue of the Annals of Neurology, found that neurofibrillary tangles in the substantia nigra, a part of the brain that is subject to cell loss in Parkinson’s disease, are associated with gait impairment in older persons with and without dementia. Neurofibrillary tangles are a classic brain abnormality seen in Alzheimer’s disease. The more tangle pathology in the substantia nigra, the more impaired the person’s gait was before death.

“Older persons without Parkinson’s disease often exhibit parkinsonian signs, such as difficulty with walking and balance (gait impairment), slowness in movements, rigidity and tremor,” said study author Dr. Julie Schneider of the Rush Alzheimer’s Disease Center. “The mild parkinsonian signs associated with aging have been historically viewed simply as an expected sign of aging rather than a disease process. Previous studies have shown that at least one of these signs, gait impairment, has harmful effects in older persons, and our current study suggests why this may be the case.”

The study included 86 autopsied subjects from the Religious Orders Study, a longitudinal clinical-pathological study of aging and dementia. Participants of the Religious Orders Study are older Catholic clergy who enroll without known dementia and agree to annual follow-up and brain donation at death.

The study included persons with and without dementia but excluded people with idiopathic Parkinson’s disease. Though less than half of the subjects had dementia, the study found nearly 78 percent of test subjects had neurofibrillary tangles in the substantia nigra. Annual neurological examinations included an assessment of parkinsonian signs using the Unified Parkinson’s Disease Rating Scale. All 86 persons had at least some evidence of parkinsonian signs before death. Gait was the most severely affected domain followed by bradykinesia (slowness in movement), rigidity, and tremor.

The study looked at the relationship between nigra tangles and each parkinsonian sign. It found that every 1,000 nigra tangles increased the gait score by more than three points. In contrast, nigra tangles were not related to bradykinesia, rigidity, or tremor. The relationship between substantia nigra tangles and gait impairment was found in persons with and without dementia.

“This study shows that the spectrum of Alzheimer’s disease is broader than we thought and may be more common than previously recognized. Alzheimer’s disease doesn’t just cause memory and cognitive problems, it is also causing motor problems in aging,” says Schneider.

“Gait problems in older people should not simply be passed over as a sign of aging. Physicians should be aware that this could be a possible early sign of Alzheimer’s disease.”

Researchers at Rush continue to study if Alzheimer’s disease pathology is impacting other motor regions of the brain and look into whether Alzheimer’s disease can only affect motor function without causing cognitive or memory declines. Another study Schneider is currently conducting involves the relationship between dopamine, which is produced in the substantia nigra, and gait changes.

More than 1000 older Catholic clergy from 40 groups across the U.S. are participating in the Religious Orders Study. The study is funded by the National Institute on Aging (NIA).All participants have agreed to annual memory testing and brain donation at the time of death. Schneider and her colleagues at the Rush Alzheimer’s Disease Center are grateful for the remarkable dedication and altruism of this unique group of people committed to helping gain insights into how the brain functions with age.

The Rush Alzheimer’s Disease Center is one of 29 NIA-supported Alzheimer’s Disease Centers across the U.S. which conduct basic science, clinical, and social and behavioral research on dementia and AD. General information on aging and aging research can be viewed at the NIA’s home website, www.nia.nih.gov.