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The Relationship of Current Cognitive Activity to Brain Amyloid Burden and Glucose Metabolism.

ABSTRACT: Several studies have investigated how lifetime cognitive engagement affects levels of amyloid-beta (A?) deposition in the brain. However, there has been some disagreement, leaving the relationship of cognitive activity (CA) to A? a largely open question. The present study investigated the relationship between CA, A? deposition, and glucose metabolism. One hundred nine cognitively normal participants underwent Pittsburgh Compound-B (PiB) and [18F]fluorodeoxyglucose-positron emission tomography and completed a questionnaire designed to measure current CA. Statistical analyses revealed significant differences in PiB retention between those in the high and low CA groups. Linear regression models revealed a significant negative relationship between PiB retention and CA and a significant positive relationship between glucose metabolism and CA. These data suggest that CA may have a direct beneficial effect on the pathophysiology of AD or reflect another underlying process that results in both higher CA and lower AD pathophysiology.

SUBMITTER: Lyons CE

PROVIDER: S-EPMC6482956 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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The Relationship of Current Cognitive Activity to Brain Amyloid Burden and Glucose Metabolism.

Lyons Clayton E CE Tudorascu Dana D Snitz Beth E BE Price Julie J Aizenstein Howard H Lopez Oscar O Lopresti Brian B Laymon Charles C Minhas Davneet D Kamboh Ilyas I Mathis Chester C Klunk William W Cohen Ann D AD

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20180507 9

Several studies have investigated how lifetime cognitive engagement affects levels of amyloid-beta (Aβ) deposition in the brain. However, there has been some disagreement, leaving the relationship of cognitive activity (CA) to Aβ a largely open question. The present study investigated the relationship between CA, Aβ deposition, and glucose metabolism. One hundred nine cognitively normal participants underwent Pittsburgh Compound-B (PiB) and [<sup>18</sup>F]fluorodeoxyglucose-positron emission to ...[more]

PMID: 29885987

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Project description:Introduction: The disconnection hypothesis of Alzheimer's disease (AD) is supported by growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals. Brain functional modalities such as [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) and electroencephalography (EEG) measure different aspects of synaptic functioning, and can contribute to understanding brain connectivity disruptions in AD. Aim: This study investigated the relationship between cortical glucose metabolism and topographical EEG measures of brain functional connectivity in subjects along AD continuum. Methods: Patients diagnosed with mild cognitive impairment (MCI) and AD (n = 67), and stratified into amyloid-positive (n = 32) and negative (n = 10) groups according to cerebrospinal fluid Aβ42/40 ratio, were assessed with [18F]FDG-PET and resting-state EEG recordings. EEG-based neuroimaging analysis involved standardized low-resolution electromagnetic tomography (sLORETA), which estimates functional connectivity from cortical sources of electrical activity in a 3D head model. Results: Glucose hypometabolism in temporoparietal lobes was significantly associated with altered EEG functional connectivity of the same regions of interest in clinically diagnosed MCI and AD patients and in patients with biomarker-verified AD pathology. The correlative pattern of disrupted connectivity in temporoparietal lobes, as detected by EEG sLORETA analysis, included decreased instantaneous linear connectivity in fast frequencies and increased lagged linear connectivity in slow frequencies in relation to the activity of remaining cortex. Conclusions: Topographical EEG measures of functional connectivity detect regional dysfunction of AD-vulnerable brain areas as evidenced by association and spatial overlap with the cortical glucose hypometabolism in MCI and AD patients. Impact statement The association between glucose hypometabolism, as evidenced by [18F]FDG-PET ([18F]fluorodeoxyglucose positron-emission tomography), and altered electroencephalography (EEG) functional connectivity metrics within temporoparietal lobes provides link between synaptic, neurophysiological, and metabolic impairment in mild cognitive impairment and Alzheimer's disease patients. This study reported alterations in EEG measures of both instantaneous and lagged linear connectivity across distinct frequency bands, both of which were shown to be important for inter- and intrahemispheric communication and function of memory systems in general. EEG-based imaging of brain functional connectivity has a potential to serve as a noninvasive, low-cost, and widely available alternative in assessing synaptic and network dysfunction in cognitively impaired patients.

Project description:Background:Previous publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism. Methods:Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-? (A?) positivity, 40 A? negative (A?-) cognitively unimpaired controls (CU; 76?±?5y), 76 A? positive (A?+) persons with MCI (76?±?7y) and 51 A??+?persons with probable AD dementia (75?±?7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with A??+?MCI and AD in comparison with A?- CU were statistically quantified via bootstrapped lateralization indices [(LI); range?-?1 (right) to 1 (left)]. Results:Compared to A?- CU, A??+?MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: -0.33) of rCMRgl declines was found in A??+?persons with probable AD dementia. Additional comparisons of A??+?groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD. Conclusions:These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.

Project description:BackgroundWe sought to investigate the possible associations of rest-activity patterns with cortical amyloid burden, medial temporal lobe (MTL) neurodegeneration, and cognitive function in patients in the early stage of cognitive impairment.MethodsRest-activity patterns were assessed in 100 participants (70 with mild cognitive impairment and 30 with mild dementia) using wrist actigraphy. All participants underwent 18F-flutemetamol positron emission tomography (PET) imaging to quantify cortical amyloid burden, structural brain magnetic resonance imaging (MRI) to quantify MTL grey matter volume, neuropsychological testing, and clinical diagnosis. We used multiple linear regression models adjusted for covariates, including demographics, diabetes, hypertension, depressive symptom, psychotropic medication, sleep medication, weekend effect, and apolipoprotein-ε allele status.FindingsAfter adjusting for possible confounders, we found that the midline estimation of statistic of rhythm (MESOR) associated positively with frontal/executive function (estimate = 1.17, standard error [SE] = 0.37, p = 0.002). The least active 5-h (L5) onset time associated positively with MTL grey matter volume and memory function (estimate = 1.24, SE = 0.33, p = 0.001, and estimate = 3.77, SE = 1.22, p = 0.003, respectively), particularly in amyloid-negative participants. Additional path analysis revealed that MTL grey matter volume partially mediated the association between L5 onset time and memory function in amyloid-negative participants.InterpretationDecreased MESOR and advanced L5 onset time may be useful as early signs of cognitive decline or MTL neurodegeneration. Furthermore, amyloid pathology may act as a moderator of the relationships between rest-activity patterns, neurodegeneration, and cognitive function.FundingKorea Centres for Disease Control and Prevention (#4845-303); National Research Foundation of Korea (2019M3C7A1031905, 2019R1A5A2026045).

Dataset Information

The Relationship of Current Cognitive Activity to Brain Amyloid Burden and Glucose Metabolism.

Publications

The Relationship of Current Cognitive Activity to Brain Amyloid Burden and Glucose Metabolism.

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