Jack, Clifford R.

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.

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all‐cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

The pathophysiological process of Alzheimer's disease (AD) is thought to begin many years before the diagnosis of AD dementia. This long “preclinical” phase of AD would provide a critical opportunity for therapeutic intervention; however, we need to further elucidate the link between the pathological cascade of AD and the emergence of clinical symptoms. The National Institute on Aging and the Alzheimer's Association convened an international workgroup to review the biomarker, epidemiological, and neuropsychological evidence, and to develop recommendations to determine the factors which best predict the risk of progression from “normal” cognition to mild cognitive impairment and AD dementia. We propose a conceptual framework and operational research criteria, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies. These recommendations are solely intended for research purposes and do not have any clinical implications at this time. It is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD, and ultimately, aid the field in moving toward earlier intervention at a stage of AD when some disease‐modifying therapies may be most efficacious.

Hippocampal atrophy is a marker of disease state and progression in Alzheimer's disease. The gold standard to measure hippocampal volume is through manual segmentation. A number of protocols to measure hippocampal volume through manual segmentation have been developed, but the marked heterogeneity of anatomical landmarks has given rise to wide variability of volume estimates. With the aim of fostering the use of hippocampal volume in routine clinical settings, an international task force is currently working on developing a harmonized protocol that will resolve and reduce the present heterogeneity. The task force will then validate the harmonized protocol, develop harmonized probabilistic hippocampal maps, and develop illustrative and educational material on the use of the harmonized protocol and maps.

OBJECTIVE To investigate the association of type 2 diabetes with subcortical infarctions. RESEARCH DESIGN AND METHODS We investigated this association in subjects with type 2 diabetes (case subjects; n = 93) and without type 2 diabetes (control subjects; n = 186), matched by age, sex, and years of education. Participants were a subset of the Mayo Clinic Study of Aging (median age 79 years) who had undergone magnetic resonance imaging. RESULTS The frequency of subcortical infarctions was 39% in case subjects and 29% in control subjects (odds ratio 1.59 [95% CI 0.91–2.75]). The association was stronger in case subjects without treatment (2.60 [1.11–6.08]) and in case subjects with diabetes-related complications (1.96 [1.02–3.74]) compared with control subjects. CONCLUSIONS These findings suggest that untreated type 2 diabetes and type 2 diabetes with complications are associated with subcortical infarctions.