Knopman, David S.

BackgroundThe six domain standard Clinical Dementia Rating Scale (CDRstd) has been successful for staging patients with the clinical syndrome of probable Alzheimer's disease (AD). The CDRstd does not specifically address language dysfunction or alteration in personality and social behaviors which are prominent in behavioral variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA).ObjectiveTo determine the value of adding domains of Language (LANG), and Behavior, Comportment, and Personality (BEHAV) to the CDRstd for the evaluation of patients with bvFTD and PPA.MethodsTwo new domains, LANG and BEHAV, were constructed to parallel the six domains sampled in the CDRstd. Clinical and neuropsychological test data were obtained from the National Alzheimer's Coordinating Center. The dataset contained information on 2550 probable AD, 88 vascular dementia, 281 dementia with Lewy body, 234 bvFTD, and 137 PPA patients.ResultsThere were 76.5% of bvFTD and 99.3% of PPA patients with abnormal ratings (>0) on the LANG domain; 90.2% of bvFTD and 63.5% of PPA had abnormal ratings on the BEHAV domain. In patients with a CDRstd sum of boxes score of <4, 53.7% of bvFTD had BEHAV domain and 78.6% of PPA patients had LANG domain scores >1. Among probable AD patients, 3.7% had LANG ratings that were ≥1 and 3.8% had BEHAV ratings that were ≥1. Logistic regression analyses showed that adding either the LANG or BEHAV domains to the CDRstd sum of boxes score significantly improved the discrimination between probable AD, bvFTD, and PPA.ConclusionsThe new LANG and BEHAV domains add value to the CDRstd for the characterization of the nonamnestic symptoms that are prominent in patients with bvFTD and PPA but that also occur in those with probable AD.

Background Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984. A broad consensus now exists that these criteria should be revised to incorporate state‐of‐the‐art scientific knowledge. Methods The National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD. The recommendation from these advisory meetings was that three separate work groups should be formed with each assigned the task of formulating diagnostic criteria for one phase of the disease: the dementia phase; the symptomatic, pre‐dementia phase; and the asymptomatic, preclinical phase of AD. Results Two notable differences from the AD criteria published in 1984 are incorporation of biomarkers of the underlying disease state and formalization of different stages of disease in the diagnostic criteria. There was a broad consensus within all three workgroups that much additional work is needed to validate the application of biomarkers for diagnostic purposes. In the revised NIA‐Alzheimer's Association criteria, a semantic and conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes that result, whereas this distinction was blurred in the 1984 criteria. Conclusions The new criteria for AD are presented in three documents. The core clinical criteria of the recommendations regarding AD dementia and MCI due to AD are intended to guide diagnosis in the clinical setting. However, the recommendations of the preclinical AD workgroup are intended purely for research purposes.