Over 80% of hospitalized COVID-19 patients have neurological symptoms, including memory loss, attention difficulties, and trouble thinking clearly that can last for months. The long-term neurological impact of the SARS-CoV-2 virus is unknown and it remains to be seen whether it would create a surge in cases of dementia and cognitive decline years later, which is already a global public health challenge. Examining the cognitive effects of the virus will help with understanding its impact on the brain and inform treatment options. The goal of the present study was to examine cognitive performance among those who have had COVID-19 via mobile-based assessments using smartphone-based cognitive tests. Participants with a previous COVID-19 diagnosis (COVID+) were expected to have worse cognitive performance at baseline than those without COVID-19 (COVID-).

Participants (n=23) with self-reported positive or negative COVID-19 statuses based on polymerase chain reaction or antigen testing were recruited from the Boston area. Inclusion criteria included access to a smartphone with an Android or iOS operation

system and to internet connectivity, along with proficiency in English. Cognitive performance was measured using Defense Automated Neurobehavioral Assessment (DANA) from AnthroTronix. Welch’s 2-sample t-test was used to compare cognitive performance among those with and without COVID-19.

The sample was comprised primarily of COVID+ (59%), female (59%), and Caucasian (50%) participants that were generally well educated (77% with a bachelor’s degree), and had >1 COVID vaccination (95%). About 50% of the sample reported symptoms of depression and mild anxiety. Results were not indicative of significant differences between COVID+ and COVID- groups at baseline: Simple Reaction Time (Immediate; M = 5.62; p = 0.81), Code Substitution (M = 1.25; p = 0.77), Procedural Reaction Time (M = -7.26; p = 0.49), Spatial Processing (M = -3.14; p = 0.50), Go No Go (M = -1.37; p = 0.89), Match to Sample (M = 2.00; p = 0.57), Memory Search (M = -2.62; p = 0.75), and Simple Reaction Time (Delayed; M = 2.99; p = 0.81).

Results indicate that cognitive performance at baseline does not differ based on COVID status, emphasizing the need for examination of longitudinal cognitive performance. Future directions include examining the impact of COVID disease severity and reinfection on cognition.

Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.

35 patients with obesity (BMI > 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.

Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p < 0.001, d = -0.64) and mI (f[34] = -2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05).

Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Novel blood-based biomarkers for Alzheimer's disease (AD) could transform AD diagnosis in the community; however, their interpretation in individuals with medical comorbidities is not well understood. Specifically, kidney function has been shown to influence plasma levels of various brain proteins. This study sought to evaluate the effect of one common marker of kidney function (estimated glomerular filtration rate (eGFR)) on the association between various blood-based biomarkers of AD/neurodegeneration (glial fibrillary acidic protein (GFAP), neurofilament light (NfL), amyloid-b42 (Ab42), total tau) and established CSF biomarkers of AD (Ab42/40 ratio, tau, phosphorylated-tau (p-tau)), neuroimaging markers of AD (AD-signature region cortical thickness), and episodic memory performance.

Vanderbilt Memory and Aging Project participants (n=329, 73±7 years, 40% mild cognitive impairment, 41% female) completed fasting venous blood draw, fasting lumbar puncture, 3T brain MRI, and neuropsychological assessment at study entry and at 18-month, 3-year, and 5-year follow-up visits. Plasma GFAP, Ab42, total tau, and NfL were quantified on the Quanterix single molecule array platform. CSF biomarkers for Ab were quantified using Meso Scale Discovery immunoassays and tau and p-tau were quantified using INNOTEST immunoassays. AD-signature region atrophy was calculated by summing bilateral cortical thickness measurements captured on T1-weighted brain MRI from regions shown to distinguish individuals with AD from normal cognition. Episodic memory functioning was measured using a previously developed composite score. Linear mixed-effects regression models related predictors to each outcome adjusting for age, sex, education, race/ethnicity, apolipoprotein E-e4 status, and cognitive status. Models were repeated with a blood-based biomarker x eGFR x time interaction term with follow-up models stratified by chronic kidney disease (CKD) staging (stage 1/no CKD: eGFR>90 mL/min/1.73m2, stage 2: eGFR=60-89 mL/min/1.73m2; stage 3: eGFR=44-59mL/min/1.73m2 (no participants with higher than stage 3)).

Cross-sectionally, GFAP was associated with all outcomes (p-values<0.005) and NfL was associated with memory and AD-signature region cortical thickness (p-values<0.05). In predictor x eGFR interaction models, GFAP and NfL interacted with eGFR on AD-signature cortical thickness, (p-values<0.004) and Ab42 interacted with eGFR on tau, p-tau, and memory (p-values<0.03). Tau did not interact with eGFR. Stratified models across predictors showed that associations were stronger in individuals with better renal functioning and no significant associations were found in individuals with stage 3 CKD. Longitudinally, higher GFAP and NfL were associated with memory decline (p-values<0.001). In predictor x eGFR x time interaction models, GFAP and NfL interacted with eGFR on p-tau (p-values<0.04). Other models were nonsignificant. Stratified models showed that associations were significant only in individuals with no CKD/stage 1 CKD and were not significant in participants with stage 2 or 3 CKD.

In this community-based sample of older adults free of dementia, plasma biomarkers of AD/neurodegeneration were associated with AD-related clinical outcomes both cross-sectionally and longitudinally; however, these associations were modified by renal functioning with no associations in individuals with stage 3 CKD. These results highlight the value of blood-based biomarkers in individuals with healthy renal functioning and suggest caution in interpreting these biomarkers in individuals with mild to moderate CKD.