Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease
New England Journal of Medicine, 07/20/2012
Bateman RJ et al. – The authors found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in cerebrospinal fluid (CSF) biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. The results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease.Methods
- In this prospective, longitudinal study, the authors analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests.
- The authors used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset).
- The authors conducted cross–sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes.
- Concentrations of amyloid–beta (A–beta)42 in the CSF appeared to decline 25 years before expected symptom onset.
- A(beta) deposition, as measured by positron–emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset.
- Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset.
- Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset.
- Global cognitive impairment, as measured by the Mini–Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.