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Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

ABSTRACT: During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.

SUBMITTER: Hosp JA

PROVIDER: S-EPMC8083602 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:The purpose of this study was to test the hypothesis that changes in cerebral vasomotor reactivity (CVMR) after 1-yr aerobic exercise training (AET) are associated with cognitive performances in individuals with amnestic mild cognitive impairment (MCI). Seventy sedentary patients with amnestic MCI were randomized to 1-yr moderate-to-vigorous intensity AET or stretching and toning (SAT) interventions. Cerebral blood flow velocity (CBFV) with transcranial Doppler, mean arterial pressure (MAP) with finapres plethysmograph, and EtCO2 with capnography were measured during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia) to assess CVMR. Cerebrovascular conductance index (CVCi) was calculated by CBFV/MAP, and CVMR by ΔCBFV/ΔEtCO2 and ΔCVCi/ΔEtCO2. Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Cardiorespiratory fitness was assessed by peak oxygen uptake (V̇o2peak). A total of 37 patients (19 in SAT and 18 in AET) completed 1-yr interventions and CVMR assessments. AET improved V̇o2peak, increased hypocapnic CVMR, but decreased hypercapnic CVMR. The effects of AET on cognitive performance were minimal when compared with SAT. Across both groups, there was a negative correlation between changes in hypocapnic and hypercapnic CVMRs in CBFV% and CVCi% (r = -0.741, r = -0.725, P < 0.001). Attenuated hypercapnic CVMR, but not increased hypocapnic CVMR, was associated with improved cognitive test scores in the AET group. In conclusion, 1-yr AET increased hypocapnic CVMR and attenuated hypercapnic CVMR which is associated cognitive performance in patients with amnestic MCI.NEW & NOTEWORTHY One-year moderate-to-vigorous intensity aerobic exercise training (AET) improved cardiorespiratory fitness (V̇o2peak), increased hypocapnic cerebral vasomotor reactivity (CVMR), whereas it decreased hypercapnic CVMR when compared with stretching and toning in patients with amnestic mild cognitive impairment (MCI). Furthermore, changes in hypercapnic CVMR with AET were correlated with improved memory and executive function. These findings indicate that AET has an impact on cerebrovascular function which may benefit cognitive performance in older adults who have high risk of Alzheimer's disease.

Project description:To examine regional cerebral blood flow (rCBF) in incident mild cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous arterial spin-labeling (CASL) magnetic resonance (MR) imaging.This study was approved by the local institutional review board and was compliant with HIPAA regulations. Informed consent was obtained. rCBF was measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were participating in a longitudinal epidemiologic study. Multisection CASL MR imaging with alternating single and double adiabatic inversion pulses and ramp-sampled echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel-level rCBF was compared among groups by using an analysis of variance design; clusters of voxels with significant group differences were identified. Multiple regression models controlled for age, sex, and presence of hypertension and related the mean rCBF in those clusters to the presence of MCI and AD.MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P = .01) with extension to the medial precuneus compared with that in control subjects. MCI patients had increased rCBF in the left hippocampus (P < .001), right amygdala (P = .007), and rostral head of the right caudate nucleus and ventral putamen and globus pallidus (P = .003) compared with that in control subjects. AD patients had decreased rCBF relative to that in control subjects and MCI patients in the left inferior parietal (P = .005), left lateral frontal (P < .001), left superior temporal (P = .001), and left orbitofrontal (P = .003) cortices. AD patients had increased rCBF in the right anterior cingulate gyrus (P = .02) compared with that in control subjects.The transition from normal cognition to AD is associated with dynamic pathologic processes in the brain, and this is reflected by both decreases and increases in rCBF. Increases in rCBF suggest a cellular and vascular compensatory process associated with incipient AD.http://radiology.rsnajnls.org/cgi/content/full/2503080751/DC1.

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Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19.

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