Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease

Abstract

A growing body of evidence suggests that a preclinical phase of Alzheimer's disease (AD) exists several years or more prior to the overt manifestation of clinical symptoms and is characterized by subtle neuropsychological and brain changes. Identification of individuals prior to the development of significant clinical symptoms is imperative in order to have the greatest treatment impact by maintaining cognitive abilities and preserving quality of life. Functional magnetic resonance imaging (fMRI) offers considerable promise as a non-invasive tool for detecting early functional brain changes in asymptomatic adults. In fact, evidence to date indicates that functional brain decline precedes structural decline in preclinical samples. Therefore, fMRI may offer the unique ability to capture the dynamic state of change in the degenerating brain. This review examines the clinical utility of blood oxygen level dependent (BOLD) fMRI in those at risk for AD as well as in early AD. We provide an overview of fMRI findings in at-risk groups by virtue of genetic susceptibility or mild cognitive decline followed by an appraisal of the methodological issues concerning the diagnostic usefulness of fMRI in early AD. We conclude with a discussion of future directions and propose that BOLD-fMRI in combination with cerebral blood flow or diffusion techniques will provide a more complete accounting of the neurovascular changes that occur in preclinical AD and thus improve our ability to reliably detect early brain changes prior to disease onset.

Differential age effects on cerebral blood flow and BOLD response to encoding: Associations with cognition and stroke risk

“…Our preliminary work in this area (for reviews, see Brown et al, 2007;Wierenga and Bondi, 2007) suggests that aging results in differences in baseline cerebral blood volume or differences in baseline 0 2 extraction fraction. According to the deoxyhemoglobin dilution model (see Brown et al, 2007, for discussion), BOLD contrast can give misleading information about the underlying metabolic activity of neurons when differences in baseline CBV or CMRO 2 are present.…”

Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease

“…For a more specific review of neuroimaging changes in the prodromal period of AD, we refer the reader to another recent critical review (see Wierenga and Bondi 2007). However, much remains to be done in characterizing the progression to AD in the Very-Old, and further clarification of the evolution of these brain and behavioral differences through the use of emerging neuropsychological (e.g., cognitive discrepancy measures) and neuroimaging (e.g., functional magnetic resonance imaging [fMRI]) techniques is needed.…”

Semantic memory activation in individuals at risk for developing Alzheimer disease

“…5 Not surprisingly, task-activated fMRI findings are inconsistent, with both increased and decreased MTL activation observed. 3 We examined the effect of FH and APOE 4 on whole-brain fMRI neural activity in cognitively asymptomatic older adults using a semantic memory (SM) task involving the discrimination of famous from unfamiliar names. This task involves minimal conscious effort and is performed at high accuracy levels.…”