Research Criteria For Alzheimer's Disease Research Articles

The Diagnostic Challenge of Frontal Alzheimer's Disease: Case Report and Literature Review

Atypical forms of Alzheimer's disease (AD) have long been described, but it's only recently that the aphasic, frontal, and visuospatial variants have been included in the clinical diagnostic and research criteria for AD. The frontal form, also known as the behavioral and/or dysexecutive form of AD, is still a poorly understood and poorly defined entity. Patients present with either behavioral or executive disorders, or both. It is now possible to establish, in vivo, a diagnosis of frontal variant AD (fv-AD) with a high degree of probability by comparing the neuropsychological profile and biomarkers. However, the neuropsychological and behavioral profile of patients with fv-AD is still poorly understood, often leading to diagnostic difficulties and confusion with the behavioral variant of frontotemporal lobar degeneration (bv-FTLD), which is the main differential diagnosis. We will illustrate the difficulties sometimes encountered in practice in the differential diagnosis between these pathologies through a clinical observation.

Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

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.

CSF tau markers are correlated with hippocampal volume in Alzheimer's disease

Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)42 level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ42:tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = −0.53) and P-tau (R = −0.56) levels. Mean HVs correlated with the CSF P-tau level (R = −0.52). No correlation was found between any brain measurement and CSF Aβ42 level. The CSF tau and P-tau levels, but not the CSF Aβ42 level, correlated with HV, suggesting that CSF tau markers reflect the neuronal loss associated with the physiopathological process of AD.

Familial Alzheimer disease in Latinos

Factors that modify risk related to APOE variants have been examined primarily in unrelated patients and controls, but seldom in family-based studies. Stroke, vascular risk factors, estrogen replacement therapy (ERT), head injury (HI), and smoking have been reported to influence risk of sporadic but not familial Alzheimer disease (AD). To examine the potential relationship between these risk factors and APOE, the authors used a family study design in a population in which the APOE-epsilon4 variant is strongly associated with risk of AD. Latino families primarily from the Caribbean Islands in which two or more living relatives had dementia were identified in the New York City metropolitan area, the Dominican Republic, and Puerto Rico. A total of 1,498 participants from 350 families underwent a clinical interview, medical and neurologic examinations, neuropsychological testing, and APOE genotyping. Diagnosis was made by consensus using research criteria for AD. APOE-epsilon4 was associated with a nearly twofold increased risk of AD. A history of stroke was also associated with a fourfold increased risk. A statistical interaction between APOE-epsilon4 and stroke was observed. Women with an APOE-epsilon4 who took ERT did not have an increased risk of AD, but in women with a history of stroke ERT was a deleterious effect modifier. APOE-epsilon4 and stroke independently increase risk of familial Alzheimer disease (AD) among Latinos, and may interact to further increase AD risk. Among women, the risk of AD associated with APOE-epsilon4 may be attenuated by a history of ERT.