Cerebral Glucose Metabolism is Associated with Verbal but not Visual Memory Performance in Community-Dwelling Older Adults

The demographics of aging suggest a great need for the early diagnosis of dementia and the development of preventive strategies. Neuropathology and structural MRI studies have pointed to the medial temporal lobe (MTL) as the brain region earliest affected in Alzheimer's disease (AD). MRI findings provide strong evidence that in mild cognitive impairments (MCI), AD-related volume losses can be reproducibly detected in the hippocampus, the entorhinal cortex (EC) and, to a lesser extent, the parahippocampal gyrus; they also indicate that lateral temporal lobe changes are becoming increasingly useful in predicting the transition to dementia. Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) imaging has revealed glucose metabolic reductions in the parieto-temporal, frontal and posterior cingulate cortices to be the hallmark of AD. Overall, the pattern of cortical metabolic changes has been useful for the prediction of future AD as well as in distinguishing AD from other neurodegenerative diseases. FDG-PET on average achieves 90% sensitivity in identifying AD, although specificity in differentiating AD from other dementias is lower. Moreover, recent MRI-guided FDG-PET studies have shown that MTL hypometabolism is the most specific and sensitive measure for the identification of MCI, while the utility of cortical deficits is controversial. This review highlights cross-sectional, prediction and longitudinal FDG-PET studies and attempts to put into perspective the value of FDG-PET in diagnosing AD-like changes, particularly at an early stage, and in providing diagnostic specificity. The examination of MTL structures, which has so far been exclusive to MRI protocols, is then examined as a possible strategy to improve diagnostic specificity. All told, there is considerable promise that early and specific diagnosis is feasible through a combination of imaging modalities.

A new diagnostic indicator of FDG PET scan abnormality, based on age-adjusted t statistics and an automated voxel-based procedure, is presented and validated in a large data set comprising 110 normal controls and 395 patients with probable Alzheimer's disease (AD) that were studied in eight participating centers. The effect of differences in spatial resolution of PET scanners was minimized effectively by filtering and masking. In controls FDG uptake declined significantly with age in anterior cingulate and frontolateral perisylvian cortex. In patients with probable AD decline of FDG uptake in posterior cingulate, temporoparietal, and prefrontal association cortex was related to dementia severity. These effects were clearly distinct from age effects in controls, suggesting that the disease process of AD is not related to normal aging. Women with probable AD had significantly more frontal metabolic impairment than men. The new indicator of metabolic abnormality in AD-related regions provided 93% sensitivity and specificity for distinction of mild to moderate probable AD from normals, and 84% sensitivity at 93% specificity for detection of very mild probable AD (defined by Mini Mental Score 24 or better). All regions related to AD severity were already affected in very mild AD, suggesting that all vulnerable areas are affected to a similar degree already at disease onset. Ventromedial frontal cortex was also abnormal. In conclusion, automated analysis of multicenter FDG PET is feasible, provides insights into AD pathophysiology, and can be used potentially as a sensitive biomarker for early AD diagnosis.

We report the first clinicopathological series of longitudinal FDG-PET scans in post-mortem (PM) verified cognitively normal elderly (NL) followed to the onset of Alzheimer's-type dementia (DAT), and in patients with mild DAT with progressive cognitive deterioration. Four NL subjects and three patients with mild DAT received longitudinal clinical, neuropsychological and dynamic FDG-PET examinations with arterial input functions. NL subjects were followed for 13 +/- 5 years, received FDG-PET examinations over 7 +/- 2 years, and autopsy 6 +/- 3 years after the last FDG-PET. Two NL declined to mild cognitive impairment (MCI), and two developed probable DAT before death. DAT patients were followed for 9 +/- 3 years, received FDG-PET examinations over 3 +/- 2 years, and autopsy 7 +/- 1 years after the last FDG-PET. Two DAT patients progressed to moderate-to-severe dementia and one developed vascular dementia. The two NL subjects who declined to DAT received a PM diagnosis of definite AD. Their FDG-PET scans indicated a progression of deficits in the cerebral metabolic rate for glucose (CMRglc) from the hippocampus to the parietotemporal and posterior cingulate cortices. One DAT patient showed AD with diffuse Lewy body disease (LBD) at PM, and her last in vivo PET was indicative of possible LBD for the presence of occipital as well as parietotemporal hypometabolism. Progressive CMRglc reductions on FDG-PET occur years in advance of clinical DAT symptoms in patients with pathologically verified disease. The FDG-PET profiles in life were consistent with the PM diagnosis.