The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to the subtle brain changes that occur in the preclinical stage of the disease. Reductions in the cerebral metabolic rate of glucose (CMRglc), a measure of neuronal function, have proven to be a promising tool in the early diagnosis of AD. In vivo brain 2-[18F]fluoro-2-Deoxy-D-glucose-positron emission tomography (FDG-PET) imaging demonstrates consistent and progressive CMRglc reductions in AD patients, the extent and topography of which correlate with symptom severity. There is increasing evidence that hypometabolism appears during the preclinical stages of AD and can predict decline years before the onset of symptoms. This review will give an overview of FDG-PET results in individuals at risk for developing dementia, including: presymptomatic individuals carrying mutations responsible for early-onset familial AD; patients with Mild Cognitive Impairment (MCI), often a prodrome to late-onset sporadic AD; non-demented carriers of the Apolipoprotein E (ApoE) epsilon4 allele, a strong genetic risk factor for late-onset AD; cognitively normal subjects with a family history of AD; subjects with subjective memory complaints; and normal elderly followed longitudinally until they expressed the clinical symptoms and received post-mortem confirmation of AD. Finally, we will discuss the potential to combine different PET tracers and CSF markers of pathology to improve the early detection of AD.
Aged ; Alleles ; Alzheimer Disease ; Apolipoproteins ; Biomarkers ; Brain ; Dementia ; Early Diagnosis ; Glucose ; Humans ; Lifting ; Memory ; Mild Cognitive Impairment ; Neuroimaging ; Neurons ; Risk Factors

BACKGROUND AND PURPOSE: Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's disease (AD) treatment. The aim of this study is 1) to find neuropsychological factors that affect the functional response to ChEI therapy and 2) to determine whether regional cerebral blood flow (rCBF) pretreatment predicts a cognitive change in response to ChEI. METHODS: We prospectively recruited 32 patients diagnosed with probable AD and treated them with donepezil, a ChEI, over one year. The patients were divided into stable (s-AD) and declined (d-AD) AD groups, based on changes in Korean version of Mini-Mental State Examination (K-MMSE) scores. Patients were assessed using the Alzheimer's Disease Co-operative Study-Activities of Daily Living (ADCS-ADL) and Seoul Neuropsychologic Screening Battery, as well as brain single photon emission computerized tomography (SPECT) at baseline and last medical evaluations. The predictors of therapeutic responses were analyzed using general linear models. RESULTS: Based on their cognitive function changes, AD patients were classified into two groups: s-AD (n=14, annual change in K-MMSE score <0.9), or d-AD (n=18, annual change in K-MMSE score > or =0.9). The s-AD at baseline showed significantly better ADCS-ADL function (p=0.04) and had a tendency to preserve frontal function compared to the d-AD group. Global Statistical Parametric Mapping analysis revealed no significant decrease of rCBF between baseline and follow-up SPECT, in either the s-AD or the d-AD groups. However, on regional perfusion analysis of baseline SPECT, the d-AD group demonstrated perfusion deficits in the supramarginal gyrus, inferior occipital gyrus, and rolandic operculum compared with the s-AD group. CONCLUSIONS: Highly preserved ADCS-ADLs predicted a better improvement in MMSE scores in response to ChEI therapy and a more positive functional response in the group with preserved frontal function. rCBF provided hints to the variable response to donepezil therapy with ChEI treatment.
Alzheimer Disease* ; Brain ; Cholinesterase Inhibitors ; Follow-Up Studies ; Humans ; Linear Models ; Mass Screening ; Neuropsychological Tests* ; Perfusion ; Prospective Studies ; Seoul ; Tomography, Emission-Computed, Single-Photon*