Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease. Bateman, R. J., Xiong, C., Benzinger, T. L., Fagan, A. M., Goate, A., Fox, N. C., Marcus, D. S., Cairns, N. J., Xie, X., Blazey, T. M., Holtzman, D. M., Santacruz, A., Buckles, V., Oliver, A., Moulder, K., Aisen, P. S., Ghetti, B., Klunk, W. E., McDade, E., Martins, R. N., Masters, C. L., Mayeux, R., Ringman, J. M., Rossor, M. N., Schofield, P. R., Sperling, R. A., Salloway, S., & Morris, J. C. The New England journal of medicine, 367(9):795–804, August, 2012.
Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease [link]Paper  doi  abstract   bibtex   
BACKGROUND The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We 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). We 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. RESULTS Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ 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. CONCLUSIONS We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)
@article{bateman2012,
	title = {Clinical and {Biomarker} {Changes} in {Dominantly} {Inherited} {Alzheimer}’s {Disease}},
	volume = {367},
	issn = {0028-4793},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474597/},
	doi = {10.1056/NEJMoa1202753},
	abstract = {BACKGROUND The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We 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). We 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. RESULTS Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ 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. CONCLUSIONS We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)},
	number = {9},
	urldate = {2023-01-27},
	journal = {The New England journal of medicine},
	author = {Bateman, Randall J. and Xiong, Chengjie and Benzinger, Tammie L.S. and Fagan, Anne M. and Goate, Alison and Fox, Nick C. and Marcus, Daniel S. and Cairns, Nigel J. and Xie, Xianyun and Blazey, Tyler M. and Holtzman, David M. and Santacruz, Anna and Buckles, Virginia and Oliver, Angela and Moulder, Krista and Aisen, Paul S. and Ghetti, Bernardino and Klunk, William E. and McDade, Eric and Martins, Ralph N. and Masters, Colin L. and Mayeux, Richard and Ringman, John M. and Rossor, Martin N. and Schofield, Peter R. and Sperling, Reisa A. and Salloway, Stephen and Morris, John C.},
	month = aug,
	year = {2012},
	pmid = {22784036},
	pmcid = {PMC3474597},
	pages = {795--804},
}
Downloads: 0
About
Documentation
Keywords
Search
Users
Terms and Conditions of Use
Privacy Policy
Sitemap
© BibBase.org 2021