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1.
Neuroimage Clin ; 34: 103002, 2022.
Article in English | MEDLINE | ID: covidwho-1821425

ABSTRACT

PURPOSE: Cerebral amyloid angiopathy (CAA) is a common neuropathological finding and clinical entity that occurs independently and with co-existent Alzheimer's disease (AD) and small vessel disease. We compared diffusion tensor imaging (DTI) metrics of the fornix, the primary efferent tract of the hippocampus between CAA, AD and Mild Cognitive Impairment (MCI) and healthy controls. METHODS: Sixty-eight healthy controls, 32 CAA, 21 AD, and 26 MCI patients were recruited at two centers. Diffusion tensor images were acquired at 3 T with high spatial resolution and fluid-attenuated inversion recovery (FLAIR) to suppress cerebrospinal fluid (CSF) and minimize partial volume effects on the fornix. The fornix was delineated with deterministic tractography to yield mean diffusivity (MD), axial diffusivity (AXD), radial diffusivity (RD), fractional anisotropy (FA) and tract volume. Volumetric measurements of the hippocampus, thalamus, and lateral ventricles were obtained using T1-weighted MRI. RESULTS: Diffusivity (MD, AXD, and RD) of the fornix was highest in AD followed by CAA compared to controls; the MCI group was not significantly different from controls. FA was similar between groups. Fornix tract volume was âˆ¼ 30% lower for all three patient groups compared to controls, but not significantly different between the patient groups. Thalamic and hippocampal volumes were preserved in CAA, but lower in AD and MCI compared to controls. Lateral ventricular volumes were increased in CAA, AD and MCI. Global cognition, memory, and executive function all correlated negatively with fornix diffusivity across the combined clinical group. CONCLUSION: There were significant diffusion changes of the fornix in CAA, AD and MCI compared to controls, despite relatively intact thalamic and hippocampal volumes in CAA, suggesting the mechanisms for fornix diffusion abnormalities may differ in CAA compared to AD and MCI.


Subject(s)
Alzheimer Disease , Cerebral Amyloid Angiopathy , Cognitive Dysfunction , Alzheimer Disease/pathology , Anisotropy , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnostic imaging , Diffusion Tensor Imaging/methods , Fornix, Brain/diagnostic imaging , Fornix, Brain/pathology , Humans
2.
Brain Behav ; 12(4): e2513, 2022 04.
Article in English | MEDLINE | ID: covidwho-1739128

ABSTRACT

OBJECTIVE: To assess FDG cerebral PET in patients suffering from cognitive impairment linked to Long COVID. The COVID pandemic has affected dozens of millions of people around the world and has resulted in the deaths of more than 3 million people. Following the acute forms, it has been reported sometimes long forms of COVID, with involvements of several organs including the brain. Neurological complications can include cognitive disturbances (brain fog) that are very common and can seriously disturb the life of patients. METHODS: Fluorodeoxyglucose PETs were performed in 3 patients with cognitive decline following COVID infection. RESULTS: We report here 3 cases of brain fog with major hypometabolic areas of the pons revealed by the cerebral FDG PET. CONCLUSION: The dysfunction of the locus coeruleus in these patients could partly explain the cognitive disorders observed. Further studies involving larger cohorts of patients suffering from cognitive dysfunction will be needed to determine if the brainstem is frequently affected in these patients.


Subject(s)
COVID-19 , Cognitive Dysfunction , Brain/diagnostic imaging , Brain Stem/diagnostic imaging , COVID-19/complications , COVID-19/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Fluorodeoxyglucose F18 , Humans , Positron-Emission Tomography , Radiopharmaceuticals
3.
J Neurol ; 269(7): 3400-3412, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1729300

ABSTRACT

BACKGROUND AND OBJECTIVES: To explore cognitive, EEG, and MRI features in COVID-19 survivors up to 10 months after hospital discharge. METHODS: Adult patients with a recent diagnosis of COVID-19 and reporting subsequent cognitive complaints underwent neuropsychological assessment and 19-channel-EEG within 2 months (baseline, N = 49) and 10 months (follow-up, N = 33) after hospital discharge. A brain MRI was obtained for 36 patients at baseline. Matched healthy controls were included. Using eLORETA, EEG regional current densities and linear lagged connectivity values were estimated. Total brain and white matter hyperintensities (WMH) volumes were measured. Clinical and instrumental data were evaluated between patients and controls at baseline, and within patient whole group and with/without dysgeusia/hyposmia subgroups over time. Correlations among findings at each timepoint were computed. RESULTS: At baseline, 53% and 28% of patients showed cognitive and psychopathological disturbances, respectively, with executive dysfunctions correlating with acute-phase respiratory distress. Compared to healthy controls, patients also showed higher regional current density and connectivity at delta band, correlating with executive performances, and greater WMH load, correlating with verbal memory deficits. A reduction of cognitive impairment and delta band EEG connectivity were observed over time, while psychopathological symptoms persisted. Patients with acute dysgeusia/hyposmia showed lower improvement at memory tests than those without. Lower EEG delta band at baseline predicted worse cognitive functioning at follow-up. DISCUSSION: COVID-19 patients showed interrelated cognitive, EEG, and MRI abnormalities 2 months after hospital discharge. Cognitive and EEG findings improved at 10 months. Dysgeusia and hyposmia during acute COVID-19 were related with increased vulnerability in memory functions over time.


Subject(s)
COVID-19 , Cognitive Dysfunction , Adult , Anosmia , COVID-19/complications , Cognition , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/pathology , Dysgeusia , Electroencephalography , Humans , Magnetic Resonance Imaging , Neuropsychological Tests , Survivors
4.
Alzheimers Res Ther ; 14(1): 36, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1724541

ABSTRACT

BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to examine sex differences in cortical thickness (CT) and memory performance. Analyses of covariance (ANCOVA) models were used to examine effects of sex and diagnosis (DX) on CT and verbal memory. For regions demonstrating significant interaction effects of sex and DX, we tested whether sex moderated cognition-thickness relationships. We used machine learning as a complementary method to explore multivariate CT differences between women and men. RESULTS: Women demonstrated greater CT in many brain regions. More specifically, men showed relatively consistent CT declines in all stages, from normal control (NC) to ADD in the bilateral cingulate cortex, bilateral temporal regions, and left precuneus; women had more stable CT in these regions between NC and mild cognitive impairment (MCI) stages, but sharper declines from MCI to ADD. Similarly, for the Rey Auditory Verbal Learning Test (RAVLT), ANCOVA analyses showed that women had significantly better immediate and delayed recall scores than men, at NC and MCI stages, but greater differences, cross-sectionally, from MCI to ADD than men. We found significant sex moderation effects between RAVLT-immediate scores and CT of right isthmus-cingulate for all subjects across DX. Partial correlation analyses revealed that increased CT of right isthmus-cingulate was associated with better verbal learning in women, driven by positron emission tomography defined amyloid positive (Aß+) subjects. Significant sex-moderation effects in cognition-thickness relationships were further found in the right middle-temporal, left precuneus, and left superior temporal regions in Aß+ subjects. Using a machine learning approach, we investigated multivariate CT differences between women and men, showing an accuracy in classification of 75% for Aß+ cognitively NC participants. CONCLUSIONS: Sex differences in memory and CT can play a key role in the different vulnerability and progression of ADD in women compared to men. Machine learning indicates sex differences in CT are most relevant early in the ADD neurodegeneration.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Neurodegenerative Diseases , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Cognitive Dysfunction/diagnostic imaging , Female , Healthy Volunteers , Humans , Male , Positron-Emission Tomography , Sex Characteristics
5.
Sensors (Basel) ; 22(4)2022 Feb 14.
Article in English | MEDLINE | ID: covidwho-1715640

ABSTRACT

The early prediction of Alzheimer's disease (AD) can be vital for the endurance of patients and establishes as an accommodating and facilitative factor for specialists. The proposed work presents a robotized predictive structure, dependent on machine learning (ML) methods for the forecast of AD. Neuropsychological measures (NM) and magnetic resonance imaging (MRI) biomarkers are deduced and passed on to a recurrent neural network (RNN). In the RNN, we have used long short-term memory (LSTM), and the proposed model will predict the biomarkers (feature vectors) of patients after 6, 12, 21 18, 24, and 36 months. These predicted biomarkers will go through fully connected neural network layers. The NN layers will then predict whether these RNN-predicted biomarkers belong to an AD patient or a patient with a mild cognitive impairment (MCI). The developed methodology has been tried on an openly available informational dataset (ADNI) and accomplished an accuracy of 88.24%, which is superior to the next-best available algorithms.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnosis , Alzheimer Disease/pathology , Biomarkers , Cognitive Dysfunction/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Memory, Short-Term
6.
J Alzheimers Dis ; 83(2): 523-530, 2021.
Article in English | MEDLINE | ID: covidwho-1459395

ABSTRACT

Coronavirus (COVID-19) has emerged as a human catastrophe worldwide, and it has impacted human life more detrimentally than the combined effect of World Wars I and II. Various research studies reported that the disease is not confined to the respiratory system but also leads to neurological and neuropsychiatric disorders suggesting that the virus is potent to affect the central nervous system (CNS). Moreover, the damage to CNS may continue to rise even after the COVID-19 infection subsides which may further induce a long-term impact on the brain, resulting in cognitive impairment. Neuroimaging techniques is the ideal platform to detect and quantify pathological manifestations in the brain of COVID-19 survivors. In this context, a scheme based on structural, spectroscopic, and behavioral studies could be executed to monitor the gradual changes in the brain non-invasively due to COVID-19 which may further help in quantifying the impact of COVID-19 on the mental health of the survivors. Extensive research is required in this direction for identifying the mechanism and implications of COVID-19 in the brain. Cohort studies are urgently required for monitoring the effects of this pandemic on individuals of various subtypes longitudinally.


Subject(s)
Brain/diagnostic imaging , COVID-19/complications , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/virology , Brain/pathology , Brain Mapping/methods , COVID-19/diagnostic imaging , COVID-19/pathology , Cognitive Dysfunction/pathology , Humans , Magnetic Resonance Spectroscopy , Oxidative Stress/physiology , SARS-CoV-2 , Survivors
7.
Brain ; 144(4): 1263-1276, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1313840

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.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/metabolism , Glucose/metabolism , Mental Status and Dementia Tests , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/psychology , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
8.
J Alzheimers Dis ; 83(2): 523-530, 2021.
Article in English | MEDLINE | ID: covidwho-1305620

ABSTRACT

Coronavirus (COVID-19) has emerged as a human catastrophe worldwide, and it has impacted human life more detrimentally than the combined effect of World Wars I and II. Various research studies reported that the disease is not confined to the respiratory system but also leads to neurological and neuropsychiatric disorders suggesting that the virus is potent to affect the central nervous system (CNS). Moreover, the damage to CNS may continue to rise even after the COVID-19 infection subsides which may further induce a long-term impact on the brain, resulting in cognitive impairment. Neuroimaging techniques is the ideal platform to detect and quantify pathological manifestations in the brain of COVID-19 survivors. In this context, a scheme based on structural, spectroscopic, and behavioral studies could be executed to monitor the gradual changes in the brain non-invasively due to COVID-19 which may further help in quantifying the impact of COVID-19 on the mental health of the survivors. Extensive research is required in this direction for identifying the mechanism and implications of COVID-19 in the brain. Cohort studies are urgently required for monitoring the effects of this pandemic on individuals of various subtypes longitudinally.


Subject(s)
Brain/diagnostic imaging , COVID-19/complications , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/virology , Brain/pathology , Brain Mapping/methods , COVID-19/diagnostic imaging , COVID-19/pathology , Cognitive Dysfunction/pathology , Humans , Magnetic Resonance Spectroscopy , Oxidative Stress/physiology , SARS-CoV-2 , Survivors
9.
Clin Neuropharmacol ; 44(5): 186-188, 2021.
Article in English | MEDLINE | ID: covidwho-1304025

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a systemic illness that implies neurological features and complications. Persistent (>48 hours) hiccups (ie, singultus or hiccoughs) have been recently described as a rare presentation of COVID-19. Even when considered benign, the frequency and duration of hiccup spells can be burdensome and sometimes difficult to treat. CASE PRESENTATION: We report the case of a 62-year-old man known by the treating physicians for vascular cognitive impairment, who consulted for progressive persistent hiccups that commenced 5 days earlier, about 24 hours after testing positive for the severe acute respiratory syndrome coronavirus 2 by real-time reverse transcription polymerase chain reaction. The patient could barely sleep because the hiccups reached the highest rate of 47 per minute in a spell lasting almost 72 hours. The patient initially received levomepromazine 25 mg by mouth, but sedation and delirium impeded the continuation of treatment, which only reduced the frequency of the hiccup spells by about 25%. Afterward, the patient was offered levosulpiride 25 mg thrice a day by mouth, resulting in a steady reduction in the hiccups rate, as well as the duration and daily frequency of spells, which disappeared after 3 days of levosulpiride treatment. COVID-19 pneumonia was moderate by chest computed tomography scan imaging and biomarkers, meriting continuous oxygen therapy, dexamethasone 6 mg once a day by mouth for 10 days, and enoxaparin 40 mg once a day, subcutaneously, for 7 days (due to elevated D-dimer serum concentration). Oxygen therapy was gradually withdrawn after 12 days. CONCLUSIONS: Oral levosulpiride is a suitable option in persistent hiccups that occur in patients with COVID-19 pneumonia. To our knowledge, this is the fourth published case of persistent hiccups as a clinical feature of COVID-19.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/complications , Hiccup/etiology , Sulpiride/analogs & derivatives , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Hiccup/diagnostic imaging , Hiccup/drug therapy , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuroimaging , Sulpiride/therapeutic use
10.
Brain ; 144(4): 1263-1276, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1169654

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.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/metabolism , Glucose/metabolism , Mental Status and Dementia Tests , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/psychology , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
11.
J Clin Neurosci ; 87: 153-155, 2021 May.
Article in English | MEDLINE | ID: covidwho-1129084

ABSTRACT

Cognitive impairment has recently attracted researchers as one of the possible neuropsychiatric manifestations of COVID-19, although how the infection perpetuates impairment of cognitive functions is still obscure. We presented a 29-year-old male patient with COVID-19 who developed new-onset transient attention deficit and memory problems following a SARS-CoV-2 infection. Structural neuroimaging was normal. MR-spectroscopy (MRS) of the bilateral DLPFC revealed significant for decreased levels of N-acetylaspartate (NAA), glutamate, and glutamate/glutamine ratio. After a follow-up without any medical treatment but with suggestions of memory exercises for three months a control MRS screening of DLPFC showed improved levels of NAA, glutamate, and glutamate/glutamine ratio. This report may suggest that cognitive deficits in SARS-CoV-2 infection can result from glutamatergic dysfunction with decreased NAA and glutamate levels in bilateral DLPFC.


Subject(s)
Aspartic Acid/analogs & derivatives , COVID-19/metabolism , Cognitive Dysfunction/metabolism , Glutamic Acid/metabolism , Prefrontal Cortex/metabolism , Adult , Aspartic Acid/metabolism , COVID-19/complications , COVID-19/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Humans , Magnetic Resonance Spectroscopy/methods , Male , Prefrontal Cortex/diagnostic imaging , Signal Transduction/physiology
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