Lilah M Besser1, John F Crary2, Charles Mock2, Walter A Kukull2. 1. From the National Alzheimer's Coordinating Center (L.M.B., C.M., W.A.K.), Department of Epidemiology, University of Washington, Seattle; and Department of Pathology (J.F.C.), Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY. lmbesser@uw.edu. 2. From the National Alzheimer's Coordinating Center (L.M.B., C.M., W.A.K.), Department of Epidemiology, University of Washington, Seattle; and Department of Pathology (J.F.C.), Fishberg Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract
OBJECTIVE: To conduct a clinicopathologic study to characterize clinical and neuropathologic features associated with cognitive impairment in participants with no neuritic amyloid plaques (primary age-related tauopathy [PART] definite) and sparse neuritic plaques (amyloid sparse). METHODS: Using the National Alzheimer's Coordinating Center database, we identified 377 individuals who were PART definite (n = 170) or amyloid sparse (n = 207), clinically examined within 1 year of death, and autopsied at 1 of 26 National Institute on Aging-funded Alzheimer's Disease Centers. Factors associated with the odds of being symptomatic (global Clinical Dementia Rating [CDR] score >0) were identified with multivariable logistic regression. RESULTS: PART-definite participants less often had a high Braak neurofibrillary tangle stage V or VI (4%) compared to amyloid sparse participants (28%, p < 0.001). Of the PART-definite participants, 98 were symptomatic and 72 asymptomatic according to their global CDR scores. PART-definite participants were less often symptomatic (58%) compared with amyloid sparse participants (80%, p < 0.001). Within the PART-definite group, independent predictors of symptomatic status included depression (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 2.15-8.19), Braak stage (aOR 1.42, 95% CI 1.04-1.95), and history of stroke (aOR 8.09, 95% CI 2.63-24.82). Within the amyloid sparse group, independent predictors of symptomatic status included education (aOR 0.80, 95% CI 0.65-0.99), Braak stage (aOR 1.91, 95% CI 1.07-3.43), and amyloid angiopathy (aOR 2.75, 95% CI 1.14-6.64). CONCLUSIONS: These findings support the hypothesis that participants with PART have an amyloid-independent dementing Alzheimer disease-like temporal lobe tauopathy.
OBJECTIVE: To conduct a clinicopathologic study to characterize clinical and neuropathologic features associated with cognitive impairment in participants with no neuritic amyloid plaques (primary age-related tauopathy [PART] definite) and sparse neuritic plaques (amyloid sparse). METHODS: Using the National Alzheimer's Coordinating Center database, we identified 377 individuals who were PART definite (n = 170) or amyloid sparse (n = 207), clinically examined within 1 year of death, and autopsied at 1 of 26 National Institute on Aging-funded Alzheimer's Disease Centers. Factors associated with the odds of being symptomatic (global Clinical Dementia Rating [CDR] score >0) were identified with multivariable logistic regression. RESULTS: PART-definite participants less often had a high Braak neurofibrillary tangle stage V or VI (4%) compared to amyloid sparse participants (28%, p < 0.001). Of the PART-definite participants, 98 were symptomatic and 72 asymptomatic according to their global CDR scores. PART-definite participants were less often symptomatic (58%) compared with amyloid sparse participants (80%, p < 0.001). Within the PART-definite group, independent predictors of symptomatic status included depression (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 2.15-8.19), Braak stage (aOR 1.42, 95% CI 1.04-1.95), and history of stroke (aOR 8.09, 95% CI 2.63-24.82). Within the amyloid sparse group, independent predictors of symptomatic status included education (aOR 0.80, 95% CI 0.65-0.99), Braak stage (aOR 1.91, 95% CI 1.07-3.43), and amyloid angiopathy (aOR 2.75, 95% CI 1.14-6.64). CONCLUSIONS: These findings support the hypothesis that participants with PART have an amyloid-independent dementing Alzheimer disease-like temporal lobe tauopathy.
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