Brain glucose metabolism in the early and specific diagnosis of Alzheimer?s disease

Abstract

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.

Altered medial temporal lobe responses during visuospatial encoding in healthy APOE*4 carriers

“…Curiously, our subjects generally reported that the route perspective was more difficult to learn then the survey perspective (unquantified). Right frontal (~BA 4, 6) and left parietal (~BA 37,39,40) areas also appeared more active during route than survey encoding in APOE*4− subjects. Failure of prefrontal activation to increase with increasing task demands has been observed in APOE*4+ subjects (44) and thus the lack of a prefrontal route/survey differential may illustrate impaired prefrontal recruitment during difficult tasks in APOE*4− subjects.…”

“…Imaging with PET and SPECT lend support to the hypothesis that the APOE*4 allele worsens AD, with both increased (29,39) and decreased (17,35,39,51) resting metabolism being reported in demented APOE*4 carriers as compared to demented non-carriers. In MCI, carriers of the APOE*4 allele reduced metabolism in the parietal-temporal regions and medial parietal lobe, including the posterior cingulate and retrosplenial area (40), perhaps reflecting greater pathologic burden and worse prognosis for these patients (for review see (10,41)). PET and SPECT metabolic studies also reveal hypometabolism in younger (47,53) and older (48,52,59) cognitively unimpaired APOE*4+ subjects.…”

Magnetic resonance spectroscopy reveals abnormalities of glucose metabolism in the Alzheimer's brain

“…Alzheimer's disease (AD) is increasingly viewed as a disorder of brain metabolism, an invariant feature of which is a profound reduction in cerebral glucose metabolism 1, 2, 3. The impairment in glucose uptake and metabolism starts decades before classic AD symptoms and worsens steadily with disease progression 4, 5, 6.…”

Nanomedicine in the diagnosis and therapy of neurodegenerative disorders

“…In reality, cognitive, motor, and behavior abnormalities underlie a variety of neurological dysfunctions associated with neurodegenerative disorders and HIV-1 infection. Thus, combinations of clinical, laboratory, and neuroimaging tests, while not irrefutably conclusive, are essential to provide diagnostic support [63][64][65][66]. A wide range of neuroimaging techniques can aid in the diagnosis of neurological complications associated with neurodegenerative disorders.…”