Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease

Abstract

This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [18F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0-23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 +/- 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21-22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.

Anatomical and functional alterations in semantic dementia: A voxel-based MRI and PET study

“…This discrepancy between both profiles suggests that functional changes may be caused partly by remote effects from the morphologically altered hippocampus, while this region would be the site of a compensatory response by neuronal plasticity [8,40,44,51]. The current findings also accord with those of Nestor et al [52] who found that metabolism and atrophy in mesial temporal ROIs were correlated in SD but not in AD.…”

A non-parametric approach for co-analysis of multi-modal brain imaging data: Application to Alzheimer's disease

“…The pattern of GM loss was consistent with similar VBM studies of AD Karas et al, 2003), with large areas of GM loss seen in the bilateral inferior and posterior parietal areas, as well as in the bilateral posterior cingulate cortices (PCC). The pattern of hypoperfusion was consistent with similar studies using PET and SPECT (Matsuda et al, 2002;Minoshima et al, 1997), with large areas of hypoperfusion in the right PCC and in the right posterior parietal area. Also a large area of hypoperfusion was seen in the right middle frontal gyrus with some extension into the superior frontal gyrus.…”

“…We also applied this approach to a multiple modality imaging data set of Alzheimer's disease (AD) (Johnson et al, 2005) which is known to alter both brain structure as well as brain function (Karas et al, 2003;Matsuda et al, 2002;Minoshima et al, 1997). We investigated local changes in gray matter (GM) volume and cerebral perfusion, obtained by T1-weighted structural MRI and arterial spin labeling (ASL) perfusion MRI, respectively.…”

Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice

“…Fluorodeoxyglucose (FDG) positron emission tomography (PET) studies find that persons with Alzheimer's disease (AD) characteristically show preferential and progressive neocortical reductions in measurements of the cerebral metabolic rate for glucose or FDG uptake (Minoshima et al, 1994(Minoshima et al, , 1995(Minoshima et al, , 1997Mielke et al, 1994;Reiman et al, 1996). The posterior cingulate cortex (PCC) appears to be particularly vulnerable (Minoshima et al, 1994(Minoshima et al, , 1997Reiman et al, 1996).…”

“…The posterior cingulate cortex (PCC) appears to be particularly vulnerable (Minoshima et al, 1994(Minoshima et al, , 1997Reiman et al, 1996). We have previously reported that cognitively normal, late-middle-aged carriers of the apolipoprotein ε4 allele (APOE4), a common AD susceptibility gene, have functional brain abnormalities in the same neocortical regions as patients with probable AD, prior to the development of cognitive symptoms , and furthermore, younger, 20-to 39-year-old carriers also show significant PET declines in these regions (Reiman et al, 2004), indicating a very early vulnerability in these cortices.…”