Cerebral perfusion and oxygenation differences in Alzheimer's disease risk

Fleisher, Adam; Podraza, Katherine M.; Bangen, Katherine J.; Taylor, Catherine L.; Sherzai, Ayesha; Sidhar, Kunal; Liu, Thomas T.; Dale, Anders M.; Buxton, Richard B.

doi:10.1016/j.neurobiolaging.2008.01.012

Cited by 164 publications

(149 citation statements)

References 70 publications

(98 reference statements)

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“…19 Conjunction analysis showed that the overlap between the 2 modalities in these areas was statistically significant. Contrary to several reports of hyperperfusion in the hippocampus for patients with prodromal AD, [27][28][29] we did not find any areas with mismatched CBF and CMRGlc, suggesting that the elevated hippocampal CBF was likely a compensatory mechanism only present in early disease stages. Complementary to the voxel-wise comparison, the ROI results showed significantly lower rCBF and rCMRGlc in the angular and posterior cingulate areas of the patients, while motor, thalamus, and basal ganglia regions were unaffected.…”

Section: Resultscontrasting

confidence: 99%

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease

Chen¹,

Wolk²,

Reddin³

et al. 2011

Neurology

224

176

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Objective:We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls.Methods: Fifteen patients with AD (mean age 72 Ϯ 6 years, Mini-Mental State Examination score[MMSE] 20 Ϯ 6) and 19 age-matched controls (mean age 68 Ϯ 6 years, MMSE 29 Ϯ 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. Results:Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. Conclusions:

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Section: Resultscontrasting

confidence: 99%

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease

Chen¹,

Wolk²,

Reddin³

et al. 2011

Neurology

224

176

View full text Add to dashboard Cite

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“…A number of studies (33,34) have shown that increases or decreases in BOLD response between young and old individuals could easily arise as artifacts of basal state factors such as metabolic rate and neurovascular coupling. With this caveat in mind, testing a main effect of group would have been difficult to interpret (this difference was sig- Fig.…”

Section: Resultsmentioning

confidence: 99%

Age-related memory deficits linked to circuit-specific disruptions in the hippocampus

Yassa

Mattfeld

Stark

et al. 2011

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

386

406

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Converging data from rodents and humans have demonstrated an age-related decline in pattern separation abilities (the ability to discriminate among similar experiences). Several studies have proposed the dentate and CA3 subfields of the hippocampus as the potential locus of this change. Specifically, these studies identified rigidity in place cell remapping in similar environments in the CA3. We used high-resolution fMRI to examine activity profiles in the dentate gyrus and CA3 in young and older adults as stimulus similarity was incrementally varied. We report evidence for "representational rigidity" in older adults' dentate/CA3 that is linked to behavioral discrimination deficits. Using ultrahigh-resolution diffusion imaging, we quantified both the integrity of the perforant path as well as dentate/CA3 dendritic changes and found that both were correlated with dentate/CA3 functional rigidity. These results highlight structural and functional alterations in the hippocampal network that predict age-related changes in memory function and present potential targets for intervention.L ong-term memory function is commonly known to deteriorate with increasing age. One of the sites that undergo the earliest changes is the hippocampus (1, 2), which has a well-known role in learning new facts and remembering events (3). Recently, electrophysiological recording studies in aged rodents have shed light on some of the possible neural mechanisms in the hippocampus that underlie this decline (1). These studies have demonstrated "rigidity" in aged CA3 place cell firing patterns in similar environments. In contrast to young CA3 place cells, which readily remap and shift their representations in these environments, aged CA3 place cells retain their original fields despite the changes in the environment. These data strongly suggest that aging is associated with a diminished capacity for pattern separation (learning new information by decorrelating similar inputs to avoid interference) and an increased propensity for pattern completion (retrieval of previously stored information from a partial cue), and further suggest that this shift could be the result of a functional imbalance in the hippocampal dentate gyrus (DG) and CA3 network.The role of hippocampal subfields in these key processes has long been hypothesized in computational models (4-7). The models suggest that the DG granule cells are capable of performing especially strong pattern separation on the distributed representations arriving from layer II entorhinal neurons, projecting this signal onto the CA3 subfield of the hippocampus via the strong mossy fiber pathway. Empirical evidence for the involvement of the DG and CA3 in pattern separation has been demonstrated by using electrophysiological recordings (8-10), immediate-early genes (11), and high-resolution functional MRI in humans (12, 13). Ablation studies using DG-specific ibotenic acid lesions (14), as well as genetic NMDA receptor knockouts (15), have additionally shown that the DG is critical for, and the likely ...

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“…Moreover, reduced left entorhinal cortex thickness was reported in a large study of child and adolescent 4-carriers relative to noncarriers (19), although this difference was influenced by larger volumes in 2-carriers. Older 4-carriers have also been reported to have increased resting cerebral blood flow relative to noncarriers (40). Sample size or age may have contributed to the lack of significant difference in morphological features or resting perfusion between 4-carriers and noncarriers.…”

Section: Discussionmentioning

confidence: 99%

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

Filippini

MacIntosh

Hough

et al. 2009

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

1,501

1,180

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The APOE 4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE 4-carriers and 18 matched noncarriers (age range: 20 -35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased ''default mode network'' (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in 4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in 4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE 4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.hippocampus ͉ memory ͉ neuroimaging ͉ resting connectivity A polipoprotein E (apoE, protein; APOE, gene) is a very-lowdensity lipoprotein that removes cholesterol from the blood and carries it to the liver for processing (1). In the central nervous system, apoE has a key role in coordinating the mobilization and redistribution of cholesterol, phospholipids, and fatty acids, and it is implicated in mechanisms such as neuronal development, brain plasticity, and repair functions (2). The human APOE gene, which is encoded on chromosome 19, has 3 allelic variants ( 2, 3, and 4). The 4 allele has been associated with a higher risk of cardiovascular disease (3), both early-onset (4) and late-onset (5) Alzheimer's disease (AD), poor outcome from traumatic brain injury (6), and age-related cognitive impairment (7).Neuroimaging studies of the APOE polymorphism in healthy subjects have largely focused on gray matter (GM) alterations in middle or late life, particularly in brain regions associated with the greatest AD pathological findings. Even in asymptomatic subjects, hippocampal and frontotemporal GM reduction has been observed in APOE 4-carriers relative to noncarriers (8). Moreover, a reduction of resting glucose metabolism was reported in young and middle-aged cognitively normal APOE 4-carriers in brain regions known to be affected by AD, including the posterior cingulate, parietal, temporal, and prefrontal cortices (9-11). fMRI task-based studies (mainly investigating memory processes) have shown greater activation in middle-aged and elderly APOE 4-carriers relative to noncarriers (12-16). Although these studies suggest an influence of the APOE 4 allele on brain structure and metabolism, they do not make clear at what age these influences initially manifest. Furthermore, although differences in structure, resting metabolism, and function have each been reported in 4-carriers relative to noncarriers, it remains to be established to what extent these characteristics interact.Thus far, reports of structural and functional eff...

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Cerebral perfusion and oxygenation differences in Alzheimer's disease risk

Cited by 164 publications

References 70 publications

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease

Voxel-level comparison of arterial spin-labeled perfusion MRI and FDG-PET in Alzheimer disease

Age-related memory deficits linked to circuit-specific disruptions in the hippocampus

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

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