The potential of functional MRI as a biomarker in early Alzheimer's disease

Sperling, Reisa A.

doi:10.1016/j.neurobiolaging.2011.09.009

Cited by 144 publications

(97 citation statements)

References 95 publications

(109 reference statements)

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“…Also, individuals with declining longitudinal EM performance had stronger age-related elevation of HC connectivity, which concurs with a previous result that elevated HC activation predicted impending hippocampal failure and subsequent memory decline (40). This notion is also consistent with crosssectional findings that hyperactivity and/or increased functional connectivity are present at early stages of mild cognitive impairment and then followed by reduced activation as cognitive impairment worsens, as seen in individuals with AD (41). With this view, it is reasonable to predict that elderly individuals with higher HC connectivity at rest will exhibit a more rapid cognitive decline or faster conversion to AD.…”

Section: Hippocampus Proper As Segmented By Freesurfersupporting

confidence: 90%

Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging

Salami

Pudas

Nyberg

2014

Proc. Natl. Acad. Sci. U.S.A.

174

170

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The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN-HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25-80 y old), we have demonstrated agerelated decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which agerelated elevation of connectivity between left and right HC was found along with attenuated HC-cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC-cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico-hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.hippocampus | DMN | resting state | episodic memory | aging T he brain is not idle at rest (1). Rather, intrinsic neuronal signaling, which manifests as spontaneous fluctuations in the blood oxygen level-dependent (BOLD) functional MRI (fMRI) signal, is ubiquitous in the human brain and consumes a substantial portion of the brain's energy (2). Coherent spontaneous activity has been revealed in a hierarchy of networks that span large-scale functional circuits in the brain (3-6). These resting-state networks (RSNs) show moderate-to-high test-retest reliability (7) and replicability (8), and some have been found in the monkey (9) and infant (10) brain. In the adult human brain, RSNs include sensory motor, visual, attention, and mnemonic networks, as well as the default mode network (DMN). There is evidence that the DMN entails interacting subsystems and hubs that are implicated in episodic memory (11-13). One major hub encompasses the posterior cingulate cortex and the retrosplenial cortex. Other hubs include the lateral parietal cortex and the medial prefrontal cortex. In addition, a hippocampus (HC) subsystem is distinct from, yet interrelated with, the major cortical DMN hubs (12,14).The functional architecture of the DMN and other RSNs is affected by different conditions, such as Alzheimer's disease (AD), Parkinson...

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Section: Hippocampus Proper As Segmented By Freesurfersupporting

confidence: 90%

Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging

Salami

Pudas

Nyberg

2014

Proc. Natl. Acad. Sci. U.S.A.

174

170

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“…Although drug-induced modulation of memoryrelated networks have been detected by fMRI [240], only few studies have demonstrated abnormal activation following, for example, long-term treatment with cholinesterase inhibitors in MCI and AD [241][242][243][244]. Therfore, additional studies are needed to test the potential role of fMRI as biomarker in clinical trials [245].…”

Section: Functional Mri Markersmentioning

confidence: 99%

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Hampel

Lista

Teipel

et al. 2014

Biochemical Pharmacology

105

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Recent advances in understanding the molecular mechanisms underlying various paths toward the pathogenesis of Alzheimer's disease (AD) has begun to provide new insight for interventions to modify disease progression. The evolving knowledge gained from multidisciplinary basic research has begun to identify new concepts for treatments and distinct classes of therapeutic targets; as well as putative disease-modifying compounds that are now being tested in clinical trials. There is a mounting consensus that such disease modifying compounds and/or interventions are more likely to be effectively administered as early as possible in the cascade of pathogenic processes preceding and underlying the clinical expression of AD. The budding sentiment is that "treatments" need to be applied before various molecular mechanisms converge into an irreversible pathway leading to morphological, metabolic and functional alterations that characterize the pathophysiology of AD. In light of this, biological indicators of pathophysiological mechanisms are desired to chart and detect AD throughout the asymptomatic early molecular stages into the prodromal and early dementia phase. A major conceptual development in the clinical AD research field was the recent proposal of new diagnostic criteria, which specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD. This paradigm shift in AD definition, conceptualization, operationalization, detection and diagnosis represents novel fundamental opportunities for the modification of interventional trial designs. This perspective summarizes not only present knowledge regarding biological markers but also unresolved questions on the status of surrogate indicators for detection of the disease in asymptomatic people and diagnosis of AD

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“…2005). Dlatego też zmniejszona aktywność obszarów odpowiedzialnych za pamięć (okolice hipokampalne) może zwiastować obniżanie się funkcji poznawczych w wyniku AD (Sperling 2011). …”

Section: Magnetyczny Rezonans Jądrowyunclassified

Mechanisms underlying Alzheimer’s disease

Bugaj¹,

Jermakow²

2016

nin

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The potential of functional MRI as a biomarker in early Alzheimer's disease

Cited by 144 publications

References 95 publications

Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging

Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging

Perspective on future role of biological markers in clinical therapy trials of Alzheimer's disease: A long-range point of view beyond 2020

Mechanisms underlying Alzheimer’s disease

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