Patients with autosomal dominant Alzheimer’s disease undergo a series of pathophysiologic changes to the brain more than 20 years prior to the clinical onset of dementia, according to a study published in the July 11 online New England Journal of Medicine. These changes occur in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism, and they ultimately lead to cognitive impairment.
The earliest change—a decline in concentrations of amyloid-b42 in the CSF—occurred 25 years before the expected onset of dementia symptoms. “These findings suggest that the diagnosis of clinical dementia is made late in the course of the biologic cascade of autosomal dominant Alzheimer’s disease,” said Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at the Washington University School of Medicine in St. Louis, and colleagues.
Findings From the DIAN Study
The researchers analyzed data from 128 participants, all of whom were enrolled in the Dominantly Inherited Alzheimer Network (DIAN) study. Each individual had a parent with a known mutation for the disease, and participants were evaluated in a cross-sectional fashion, with estimates of stage of disease made by the Estimated Years to Symptom onset (the age of the participant minus the age of the parent at first symptom onset).
At baseline, the participants underwent clinical and cognitive assessment, brain imaging, and CSF and blood tests. Clinical assessments of cognitive change were conducted with the Clinical Dementia Rating scale and with a comprehensive battery of neuropsychologic tests, including the Mini-Mental State Examination (MMSE). MRI scans, as well as PET imaging with fluorodeoxyglucose and Pittsburgh compound B, were used to determine region of interest metabolic activity and amyloid deposition, respectively.