Early Detection of Alzheimer's Disease: A Statistical Approach Using Positron Emission Tomographic Data

Abstract

Correlational analysis of regional cerebral glucose metabolism (rCMRglc) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMRglc interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMRglc interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMRglc interdependencies. We applied this new statistical procedure to resting rCMRglc PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability >0.70). The results suggest that this statistical approach may be useful for the early detection of AD.

Mitochondrial DNA Oxidative Damage and Repair in Aging and Alzheimer's Disease

“…This notion is supported by an extensive literature which reports that AD is characterized by reduced cerebral energy metabolism (8), impaired activities of the tricarboxylic acid cycle enzymes (25,121,162), and defects in the mitochondrial ETC (21,32,45,146,96,193). The most consistent defect at ETC level is the decline in cytochrome c oxidase (COX) activity, an effect that is positively correlated with Ab concentration, as determined by in vitro studies (30).…”

PET Network Abnormalities and Cognitive Decline in Patients with Mild Cognitive Impairment

“…Other investigators have utilized multivariate analytic techniques to distinguish AD from control subjects (Azari et al, 1993;Grady et al, 2001) and to predict conversion to AD (Johnson et al, 1998). In a Tc-HMPAO SPECT study, the pattern derived from multivariate analysis showed 84.4% accuracy in discriminating 27 questionable dementia patients who did not progress from 18 questionable dementia subjects who converted to AD during 2 years of follow-up (Johnson et al, 1998).…”

[18F]Fluorodeoxyglucose Positron Emission Tomography in Alzheimer Disease and Related Disorders

“…Using the visual semiquantitative method, sensitivity was 92%, specificity was 83%, and accuracy was 87% (Azari et al, 1993;Burdette et al, 1996;Fazekas et al, 1989;Kippenhan et al, 1992;Scheurich et al, 2005). Quantitative methods showed that overall sensitivity was 94%, specificity was 87%, and accuracy was 91% (Duara et al, 1989;Herholz et al, 1990Herholz et al, , 1993Ishii et al, 2006;Kawachi et al, 2006;Mielke et al, 1994;Minoshima et al, 1995;Mosconi et al, 2005;Ng et al, 2007;Ohyama et al, 2000;Szelies et al, 1994;von Borczyskowski et al, 2006).…”