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

Abstract

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H 2 15 O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H 2 15 O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Pso0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.

Neural network approaches and their reproducibility in the study of verbal working memory and Alzheimer’s disease

“…Overall, these results of the forward application to the MMCI replication sample provide good support for the use of the AD-related CBF pattern as a prognostic and diagnostic tool (31).…”

“…Because sufficient follow-up information was available from the time the PET scans were performed, we also investigated whether baseline expression of the AD-related pattern could predict disease progression in the MMCI subjects (31). We first investigated whether the baseline expression of the AD-related CBF pattern in the MMCI subjects could predict their conversion to AD status (CDR=1).…”

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

“…Further, a default-mode resting network, identified with Independent Components Analysis from normal elders, has been shown to be abnormal in AD subjects (Greicius et al, 2004) and could therefore serve as a sensitive biomarker. Apart from these analyses, there recently has been work from our (Devanand et al, 2006;Scarmeas et al, 2004) and other laboratories (Huang et al, 2007;Kerrouche et al, 2006) utilizing principal components analysis (PCA) for the detection of dementia. Our aim was to build on our and other groups' successful usage of PCA for the detection of neurodegenerative diseases.…”

“…the more the MCI subjects expressed the AD-related patterns, the worse they performed. (2) Further, subject expression of the AD-pattern in the MCI subjects could also predict future decline in subjects' neuropsychological scores (Devanand et al, 2006): the more subjects expressed the AD-related pattern at baseline, the faster they declined. These findings give a brief glimpse of the potential of multivariate analytic approaches.…”

Resting metabolic connectivity in Alzheimer’s disease

“…Several lines of evidence suggest that in the preclinical stage of AD, beta amyloid deposition is present mainly in DMN regions [14] and that impairment of the DMN may represent a sensitive and specific biomarker of incipient AD. Among the methods proposed for studying the DMN in AD, resting-state fMRI reflects spontaneous neuronal activity and/or the endogenous neurophysiological processes of the human brain in the resting state (see Liu et al for a review [15]), while H 2 15 O PET studies allow analysis of covariance of rest-specific regional cerebral blood flow patterns [16]. Recent combined resting-state fMRI and amyloid PET studies have provided, in vivo, further evidence of the pathophysiological meaning of impaired connectivity in AD.…”