Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

Abstract

Summary: Recent advances in understanding the molecular biology of Alzheimer's disease (AD) offer the promise of useful therapeutic intervention in the foreseeable future. Hence, improved methods for early diagnosis and noninvasive surrogates of disease severity in AD have become more imperative. Various quantitative magnetic resonance (MR) techniques that measure the anatomic, biochemical, microstructural, functional, and blood-flow changes are being evaluated as possible surrogate measures of disease progression. Cross-sectional and longitudinal studies indicate that MR-based volume measurements are potential surrogates of disease progression in AD, starting from the preclinical stages. The validity of MR-based volumetry as a surrogate marker for therapeutic efficacy in AD remains to be tested in a positive disease-modifying drug trial. Recent development of amyloid imaging tracers for positron emission tomography has been a major breakthrough in the field of imaging markers for AD. Efforts to image plaques are also underway in MR imaging. As with indirect MR measures, these approaches of directly imaging the pathological substrate will need to undergo a validation process with longitudinal studies to prove their usefulness as surrogate markers in AD.

Dementia Update 2005

“…A decrease in NAA in the posterior cingulate gyrus has been reported for mild-moderate AD. 107 Different patterns of metabolite ratio changes may distinguish various dementias. 111 Other MR methods that are being explored for usefulness in early diagnosis and for measuring AD progression are diffusion tensor imaging or diffusion-weighted imaging, where the diffusivity of water molecules appears increased in the cerebral white matter of AD patients compared with controls, and functional MR (fMRI), which measures brain activation patterns (using paradigms involving memory, semantic processing, or visual responses).…”

Entorhinal and transentorhinal atrophy in mild cognitive impairment using longitudinal diffeomorphometry

“…Against this background, localized anatomic change in the medial temporal lobe observed using structural magnetic resonance imaging (MRI) has provided an indirect measure of neuronal injury [7,8]. In particular, entorhinal cortical atrophy has been identified as one of the MRI measures that predicts longitudinal progression among symptomatic cases, with greater atrophy associated with greater clinical disease severity [9][10][11][12] (also see recent review [13]).…”

Magnetic Resonance Imaging Traits in Siblings Discordant for Alzheimer Disease

“…Neuroimaging methods can be helpful in characterizing brain regions affected by Alzheimer disease (AD). 1,2 Hippocampal atrophy observed by magnetic resonance imaging (MRI), for example, is considered an early and specific marker of the AD process 3-6 that correlates with impairments in memory function 7 and AD pathology. 8,9 Crosssectional and longitudinal measures of cerebral atrophy also differ between AD patients and age-matched controls 5,[10][11][12][13][14][15] and are associated with the rate of cognitive deterioration.…”

“…[16][17][18] These data suggest that hippocampal and cerebral atrophy could serve as biological markers of early AD pathology. 19 White matter hyperintensities (WMH) which are abnormalities of cerebral white matter are frequently seen in normal aging and are commonly attributed to cerebrovascular disease (CVD), [20][21][22] WMH also have been associated with AD, 23 but these associations are controversial. 24 MRI atrophy and WMH have not been examined in a family-based cohort of patients and unaffected family members who share environmental and genetic backgrounds.…”