Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease

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Abstract

Alzheimer's disease (AD) is caused by a cascade of changes to brain integrity. Neuroimaging biomarkers are important in diagnosis and monitoring the effects of interventions. As memory impairments are among the first symptoms of AD, the relationship between imaging findings and memory deficits is important in biomarker research. The most established magnetic resonance imaging (MRI) finding is hippocampal atrophy, which is related to memory decline and currently used as a diagnostic criterion for AD. While the medial temporal lobes are impacted early by the spread of neurofibrillary tangles, other networks and regional changes can be found quite early in the progression. Atrophy in several frontal and parietal regions, cortical thinning, and white matter alterations correlate with memory deficits in early AD. Changes in activation and connectivity have been detected by functional MRI (fMRI). Task-based fMRI studies have revealed medial temporal lobe hypoactivation, parietal hyperactivation, and frontal hyperactivation in AD during memory tasks, and activation patterns of these regions are also altered in preclinical and prodromal AD. Resting state fMRI has revealed alterations in default mode network activity related to memory in early AD. These studies are limited in part due to the historic inclusion of patients who had suspected AD but likely did not have the disorder. Modern biomarkers allow for more diagnostic certainty, allowing better understanding of neuroimaging markers in true AD, even in the preclinical stage. Larger patient cohorts, comparison of candidate imaging biomarkers to more established biomarkers, and inclusion of more detailed neuropsychological batteries to assess multiple aspects of memory are needed to better understand the memory deficit in AD and help develop new biomarkers. This article reviews MRI findings related to episodic memory impairments in AD and introduces a new study with multimodal imaging and comprehensive neuropsychiatric evaluation to overcome current limitations.

Highlights

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Memory impairments are among the first symptoms of Alzheimer's disease.
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Structural and functional changes can be detected in prodromal Alzheimer's disease by imaging.
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Imaging changes in early Alzheimer's disease are related to memory deficits.

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Most cited references 99

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Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Kim Celone, Vince D. Calhoun, Bradford Dickerson … (2006)

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

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Functional deactivations: change with age and dementia of the Alzheimer type.

Cindy Lustig, Abraham Snyder, Mehul Bhakta … (2003)

Young adults typically deactivate specific brain regions during active task performance. Deactivated regions overlap with those that show reduced resting metabolic activity in aging and dementia, raising the possibility of a relation. Here, the magnitude and dynamic temporal properties of these typically deactivated regions were explored in aging by using functional MRI in 82 participants. Young adults (n = 32), older adults without dementia (n = 27), and older adults with early-stage dementia of the Alzheimer type (DAT) (n = 23) were imaged while alternating between blocks of an active semantic classification task and a passive fixation baseline. Deactivation in lateral parietal regions was equivalent across groups; in medial frontal regions, it was reduced by aging but was not reduced further by DAT. Of greatest interest, a medial parietal/ posterior cingulate region showed differences between young adults and older adults without dementia and an even more marked difference with DAT. The temporal profile of the medial parietal/posterior cingulate response suggested that it was initially activated by all three groups, but the response in young adults quickly reversed sign, whereas DAT individuals maintained activation throughout the task block. Exploratory whole-brain analyses confirmed the importance of medial parietal/posterior cingulate cortex differences in aging and DAT. These results introduce important opportunities to explore the functional properties of regions showing deactivations, how their dynamic functional properties relate to their baseline metabolic rates, and how they change with age and dementia.

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Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment.

Maja A. A. Binnewijzend, Menno Schoonheim, Ernesto Sanz-Arigita … (2012)

Regional functional connectivity (FC) of 39 patients with Alzheimer's disease (AD), 23 patients with mild cognitive impairment (MCI), and 43 healthy elderly controls was studied using resting-state functional magnetic resonance imaging (rs-fMRI). After a mean follow-up of 2.8 ± 1.9 years, 7 MCI patients converted to AD, while 14 patients remained cognitively stable. Resting-state functional magnetic resonance imaging scans were analyzed using independent component analysis (ICA), followed by a "dual-regression" technique to create and compare subject-specific maps of each independent spatiotemporal component, correcting for age, sex, and gray matter atrophy. AD patients displayed lower FC within the default-mode network (DMN) in the precuneus and posterior cingulate cortex compared with controls, independent of cortical atrophy. Regional FC values of MCI patients were numerically in between AD patients and controls, but only the difference between AD and stable MCI patients was statistically significant. Correlation with cognitive dysfunction demonstrated the clinical relevance of FC changes within the DMN. In conclusion, clinically relevant decreased FC within the DMN was observed in AD. Copyright © 2012 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Ece Bayram

Journal

Journal ID (nlm-ta): Alzheimers Dement (N Y)

Journal ID (iso-abbrev): Alzheimers Dement (N Y)

Title: Alzheimer's & Dementia : Translational Research & Clinical Interventions

Publisher: Elsevier

ISSN (Electronic): 2352-8737

Publication date PMC-release: 14 June 2018

Publication date Collection: 2018

Publication date (Electronic): 14 June 2018

Volume: 4

Pages: 395-413

Affiliations

[1]Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA

Author notes

[∗ ]Corresponding author. Tel.: 702-701-7892; Fax: 782 483 6010. bayrame@ 123456ccf.org

Article

Publisher ID: S2352-8737(18)30025-8

DOI: 10.1016/j.trci.2018.04.007

PMC ID: 6140335

PubMed ID: 30229130

SO-VID: fd72337a-0a1c-4f55-adac-0d02a732ea04

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Current understanding of magnetic resonance imaging biomarkers and memory in Alzheimer's disease

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Karger: Neurology and Neuroscience

Most cited references 99

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Functional deactivations: change with age and dementia of the Alzheimer type.

Resting-state fMRI changes in Alzheimer's disease and mild cognitive impairment.

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