The concept of FDG-PET endophenotype in Alzheimer's disease.
ABSTRACT Often viewed as a potential tool for preclinical diagnosis in early asymptomatic stages of Alzheimer's disease (AD), the term "endophenotype" has acquired a recent popularity in the field. In this review, we analyze the construct of endophenotype-originally designed to discover genes, and examine the literature on potential endophenotypes for the late-onset form of AD (LOAD). We focus on the [18F]-fluoro-2-deoxyglucose (FDG) PET technique, which shows a characteristic pattern of hypometabolism in AD-related regions in asymptomatic carriers of the ApoE E4 allele and in children of AD mothers. We discuss the pathophysiological significance and the positive predictive accuracy of an FDG-endophenotype for LOAD in asymptomatic subjects, and discuss several applications of this endophenotype in the identification of both promoting and protective factors. Finally, we suggest that the term "endophenotype" should be reserved to the study of risk factors, and not to the preclinical diagnosis of LOAD.
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ABSTRACT: In May 2012, the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia brought together in Montreal experts from around Canada to update Canadian recommendations for the diagnosis and management of patients with neurodegenerative conditions associated with deterioration of cognition. Multiple topics were discussed. The present paper is a highly condensed version of those recommendations that were produced to support discussions in the field of neuroimaging for clinical diagnosis of those conditions.Alzheimer's Research and Therapy 07/2013; 5(Suppl 1):S3. · 4.39 Impact Factor
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ABSTRACT: Alzheimer's disease (AD) is a devastating public health problem that affects over 5.4 million Americans. Depression increases the risk of Mild Cognitive Impairment (MCI) and AD. By understanding the influence of depression on cognition, the potential exists to identify subgroups of depressed elders at greater risk for cognitive decline and AD. The current study sought to: 1) clinically identify a sub group of geriatric patients who suffer from depression related cognitive impairment; 2) cross validate this depressive endophenotype of MCI/AD in an independent cohort. Data was analyzed from 519 participants of Project FRONTIER. Depression was assessed with the GDS30 and cognition was assessed using the EXIT 25 and RBANS. Five GDS items were used to create the Depressive endophenotype of MCI and AD (DepE). DepE was significantly negatively related to RBANS index scores of Immediate Memory (B=-2.22, SE=.37, p<0.001), visuospatial skills (B=-1.11, SE=0.26, p<0.001), Language (B=-1.03, SE=0.21, p<0.001), Attention (B=-2.56, SE=0.49, p<0.001), and Delayed Memory (B=-1.54, SE = 037, p<0.001), and higher DepE scores were related to poorer executive functioning (EXIT25; B=0.65, SE=0.19, p=0.001). DepE scores significantly increased risk for MCI diagnosis (odds ratio [OR] = 2.04; 95% CI=1.54-2.69). Data from 235 participants in the TARCC (Texas Alzheimer's Research & Care Consortium) were analyzed for cross-validation of findings in an independent cohort. The DepE was significantly related to poorer scores on all measures, and a significantly predicted of cognitive change over 12- and 24-months. The current findings suggest that a depressive endophenotype of MCI and AD exists and can be clinically identified using the GDS-30. Higher scores increased risk for MCI and was cross-validated by predicting AD in the TARCC. A key purpose for the search for distinct subgroups of individuals at risk for AD and MCI is to identify novel treatment and preventative opportunities.PLoS ONE 01/2013; 8(7):e68848. · 3.53 Impact Factor
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ABSTRACT: We explored resting-state metabolic connectivity in prodromal Alzheimer's disease (pAD) patients and in healthy controls (CTR), through a voxel-wise interregional correlation analysis of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) by means of statistical parametric mapping. Baseline 18F-fluorodeoxyglucose-positron emission tomography of 36 patients with amnestic mild cognitive impairment who converted to Alzheimer's disease (AD) dementia after an average time of 2 years (pAD) and of 105 CTR were processed. The area of hypometabolism in pAD showed less metabolic connectivity in patients than in CTR (autocorrelation and correlation with large temporal and frontal areas, respectively). pAD patients showed limited correlation even in selected nonhypometabolic areas, including the hippocampi and the dorsolateral prefrontal cortex (DLFC). On the contrary, in CTR group correlation was highlighted between hippocampi and precuneus/posterior cingulate and frontal cortex, and between dorsolateral prefrontal cortex and caudate nuclei and parietal cortex. The reduced metabolic connections both in hypometabolic and nonhypometabolic areas in pAD patients suggest that metabolic disconnection (reflecting early diaschisis) may antedate remote hypometabolism (early sign of synaptic degeneration).Neurobiology of aging 02/2012; 33(11):2533-50. · 5.94 Impact Factor