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Alzheimer's Disease (AD) in elderly adds substantially to socio-economic burden necessitating early diagnosis. While recent studies in rodent models of AD have suggested diagnostic and therapeutic value for gamma rhythms in brain, the same has not been rigorously tested in humans. In this case-control study, we recruited a large population (N=244; 106 females) of elderly (>49 years) subjects from the community, who viewed large gratings that induced strong gamma oscillations in their electroencephalogram (EEG). These subjects were classified as healthy (N=227), mild-cognitively-impaired (MCI; N=12) or AD (N=5) based on clinical history and Clinical Dementia Rating scores. Surprisingly, stimulus-induced gamma rhythms, but not alpha or steady-state visually evoked responses, were significantly lower in MCI/AD subjects compared to their age and gender matched controls. This reduction was not due to differences in eye-movements or baseline power. Our results suggest that gamma could be used as potential screening tool for MCI/AD in humans.

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AbstractGamma rhythms (∼20-70 Hz) have been reported to be abnormal in mental disorders such as autism and schizophrenia in humans, and Alzheimer’s disease (AD) models in rodents. However, the effect of normal aging on these oscillations is not known, especially for elderly subjects (>49 years) for which AD is most prevalent. In a first large-scale (236 subjects; 104 females) electroencephalogram (EEG) study on gamma oscillations on elderly subjects (aged 50-88 years), we presented full-screen Cartesian gratings that induced two distinct gamma oscillations (slow: 20-34 Hz and fast: 36-66 Hz). Power and centre frequency significantly decreased with age for both slow and fast gamma, but not alpha (8-12 Hz). Reduction was more salient for fast gamma than slow. These results were independent of microsaccades and pupillary reactivity to stimulus, as well as variations in power spectral density with age. Steady-state visual evoked potentials (SSVEPs) also reduced with age. These results are crucial first steps towards using gamma/SSVEPs as biomarkers of cognitive decline in elderly.Significance statementNo study in humans has examined visual narrow-band gamma oscillations with healthy aging in elderly subjects. In a first large-scale (236 subjects) EEG study on stimulus-induced narrow band gamma in cognitively normal elderly (>49 years) humans, we show that both power and centre frequency of slow and fast gamma (20-34 Hz and 36-66 Hz respectively) decrease with age, but alpha power does not. Steady-state visual evoked potential (SSVEPs) in gamma range also decrease with age. Any EEG-based biomarker is accessible and affordable to patients of a wide socio-economic spectrum. Our results are important steps for developing such screening/diagnostic tests for aging-related diseases, like Alzheimer’s disease.

Background: COVID-19 related strokes (CORS) are increasingly being diagnosed across the world. The knowledge about the clinical profile, imaging findings and outcomes are still evolving. Here we describe the characteristics of a cohort of 62 CORS patients from 13 hospitals, from Bangalore city, south India. Objective: To describe the clinical profile, neuroimaging findings, interventions and outcomes in CORS patients Methods: Multicenter retrospective study of all CORS patients from 13 hospitals from south India from 1st June 2020 to 31st August 2020.Demographic, clinical, laboratory and neuroimaging data were collected along with treatment administered and outcomes. SARS-CoV-2 infection was confirmed in all cases by RT- PCR testing. The data obtained from the case records were entered in SPSS 25 for statistical analysis. Results: During the 3-month period we had 62 CORS patients, across 13 centers. 60 (97%) had ischemic strokes while 2 (3%) had hemorrhagic strokes. The mean age of patients was 55.66 ±13.20 years, with 34 (77.4%) males. 26 % (16/62) of patients did not have any conventional risk factors for stroke. Diabetes Mellitus was seen in 54.8%, hypertension was present in 61.3%, coronary artery disease in 8% and atrial fibrillation in 4.8%. Base line NIHSS score was 12.7 ±6.44. Stroke severity was moderate (NIHSS 5-15) in 27 (61.3%) patients, moderate to severe (NIHSS 16-20) in 13 (20.9%) patients and severe (NIHSS 21-42) in 11(17.7%) patients. According to TOAST classification for ischemic strokes, 48.3% was stroke of undetermined etiology, 36.6% had large artery atherosclerosis, 10% had small vessel occlusion and 5% had cardioembolic strokes. 3 (5%) received intravenous thrombolysis with tenecteplase 0.2 mg/Kg and 3 (5%) underwent mechanical thrombectomy two endovascular and one surgical. Duration of hospital stay was 16.16± 6.39 days. 16% (13/62) died in hospital, while 37 (59.7%) had a mRS of 3-5 at discharge. Hypertension, atrial fibrillation and higher baseline NIHSS scores were associated with increased mortality. A comparison to 111 historical controls during the non COVID period showed a higher proportion of strokes of undetermined etiology, higher mortality and higher morbidity in CORS patients. Conclusion:CORS are increasing being recognized in developing countries like India. Stroke of undetermined etiology appears to be the most common TOAST subtype of CORS. CORS were more severe in nature and resulted in higher mortality and morbidity. Hypertension, atrial fibrillation and higher baseline NIHSS scores were associated with increased mortality.

Background:Hashimoto encephalopathy (HE) is a poorly understood and often misdiagnosed entity with variable clinical spectrum. There are many uncertainties that still remain about this condition and the pathological significance of thyroid peroxidase (TPO) antibody.Objective:To characterize the clinical, laboratory and radiologic findings in patients with HE.Design:Retrospective analysis of clinical features and diagnostic test data.Main Outcome Measures:Clinical features, laboratory, radiologic, electroencephalography (EEG) findings associated with HE and therapeutic outcome.Results:Thirteen consecutive patients were identified as having HE. The median age at onset was 48.5 years (range, 19–62 years). There was a female preponderance (76.9%). Clinical manifestations were cognitive impairment and behavioral changes in 10 (76.9%), sleep disturbance in 9 (69.2%), seizures in 6 (46.1%), headache in 4 (30.8%), psychosis or paranoia in 5 (38.5%), transient symptoms in 6 (46.1%), myoclonus in 4 (30.8%), ataxia or gait disorder in 4 (30.8%). The most frequent laboratory abnormalities were increased TPO (n = 13) in all cases, increased thyroid stimulating hormone levels (n = 6), and increased erythrocyte sedimentation rate (n = 5). The cerebrospinal fluid protein level was elevated in 8 of 9 patients (88.8%). Magnetic resonance imaging abnormalities were present in 2 patients (15.4%). EEG changes were seen in 7 patients (53.8%). All but two patients showed significant therapeutic benefit with steroids.Conclusions:HE has a wide range of clinical, laboratory, and radiologic findings. All patients with an unexplained encephalopathy should be screened for this condition as treatment response is excellent. To the best of our knowledge, this is the largest single center clinical series of HE from the Indian subcontinent.

Background Out of several neuroprotective drugs (NPDs) studied in animals and humans, four NPDs (citicoline, edaravone, cerebrolysin, and minocycline) have been found to have beneficial effects in acute ischemic stroke (AIS). Objective The purpose is to evaluate the efficacy of citicoline, edaravone, minocycline, and cerebrolysin compared with placebo in patients with middle cerebral artery (MCA) territory AIS. Materials and Methods This was a prospective, single center, single-blinded, and hospital-based study. One hundred patients with MCA territory AIS with 20 patients in each group including control group were included. Barthel index (BI), National Institute of Health Stroke Scale (NIHSS) score, and modified Rankin Scale score were recorded at admission, at day 11 and after 90 days. Results The mean NIHSS score was significantly lesser at day 11 and after 90 days in citicoline, edaravone, and cerebrolysin group in comparison with placebo. Similarly, the mean BI score was significantly higher at day 11 and after 90 days in citicoline, edaravone, and cerebrolysin group in comparison with placebo. In minocycline group, there was no significant change in the NIHSS score and BI score at day 11 and after 90 days. Conclusion There was significant improvement in the functional outcome of patients with AIS involving MCA territory at 90 days receiving citicoline, edaravone, and cerebrolysin. However, minocycline did not offer the same efficacy as compared with other neuroprotective agents.

Visual stimulus-induced gamma oscillations in electroencephalogram (EEG) recordings have been recently shown to be compromised in subjects with preclinical Alzheimer’s Disease (AD), suggesting that gamma could be an inexpensive biomarker for AD diagnosis provided its characteristics remain consistent across multiple recordings. Previous magnetoencephalography studies in young subjects have reported consistent gamma power over recordings separated by a few weeks to months. Here, we assessed the consistency of stimulus-induced slow (20–35 Hz) and fast gamma (36–66 Hz) oscillations in subjects (n = 40) (age: 50–88 years) in EEG recordings separated by a year, and tested the consistency in the magnitude of gamma power, its temporal evolution and spectral profile. Gamma had distinct spectral/temporal characteristics across subjects, which remained consistent across recordings (average intraclass correlation of ~ 0.7). Alpha (8–12 Hz) and steady-state-visually-evoked-potentials (SSVEPs) were also reliable. We further tested how EEG features can be used to identify two recordings as belonging to the same versus different subjects and found high classifier performance (AUC of ~ 0.89), with temporal evolution of slow gamma and spectral profile being most informative. These results suggest that EEG gamma oscillations are reliable across sessions separated over long durations and can also be a potential tool for subject identification.