J Clin Neurol.  2009 Dec;5(4):153-166. 10.3988/jcn.2009.5.4.153.

Current Challenges for the Early Detection of Alzheimer's Disease: Brain Imaging and CSF Studies

• Mistur R
• Mosconi L
• Santi SD
• Guzman M
• Li Y
• Tsui W
• de Leon MJ

• KMID: 2287644
• DOI: http://doi.org/10.3988/jcn.2009.5.4.153

Abstract

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.

Keyword

Alzheimer disease; PET; CSF markers

MeSH Terms

Aged
Alleles
Alzheimer Disease
Apolipoproteins
Biomarkers
Brain
Dementia
Early Diagnosis
Glucose
Humans
Lifting
Memory
Mild Cognitive Impairment
Neuroimaging
Neurons
Risk Factors
Apolipoproteins
Glucose

Figure

• 

  Fig. 1 Two representative cases: magnetic resonance image (MRI, left column), FDG-PET (middle column) and PIB-PET (right column) of a normal control (top row) and an AD patient (bottom row). FDG: 2-[18F]fluoro-2-Deoxy-D-glucose, PIB: Pittsburgh Compound-B, AD: Alzheimer's disease.

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