Faculty Bibliography

Background and Aims: White matter hyperintensities (WMH) on the MRI FLAIR sequence may reflect cerebral small vessel disease, impacting age-related cognitive decline and Alzheimer's disease (AD). However, it is not clear how WMH in normal individuals relates to subjective cognitive decline (SCD), proposed to be a prodromal stage of AD.
Method(s): We performed a cross-sectional analysis of 194 cognitively normal elder volunteers with SCD seen in the NYU Alzheimer's Disease Center from 1/2017-10/2019. Evaluations included medical history, neuropsychological testing, SCD ratings, and MRI. They were divided into two groups based on extent of WMH on MRI axial FLAIR: moderate-to-severe (n=29) and none-to-mild (n=165).
Result(s): The groups performed similarly on cognitive testing, and had equivalent rates of hippocampal atrophy on MRI. Hypertension was more prevalent in the moderate-severe WMH group (67% vs. 25%, p=0.003). Moderate-severe WMH subjects had slightly higher SCD magnitude measured on the Brief Cognitive Rating Scale (21.68 vs. 20.53, p=0.04). They also expressed more concern about nonamnestic cognition on the Cognitive Change Index, questions 13-20 (13.35 vs. 10.92, p=0.003), specifically with everyday decision making (p=0.006) and shifting from one activity to the next (p=0.007). On the Geriatric Depression Scale, they were more likely to endorse emptiness (11% vs. 2%, p=0.04) and not feeling wonderful to be alive now (18% vs. 6%, p=0.049).
Conclusion(s): In SCD, WMH associates with hypertension and contributes to the character of cognitive concern and concomitant affective symptoms. WMH should be further studied as an important vascular modulator of this prodromal stage of AD

BACKGROUND:Early identification of vasospasm prior to symptom onset would allow prevention of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH). Dynamic cerebral autoregulation (DCA) is a noninvasive means of assessing cerebral blood flow regulation by determining independence of low-frequency temporal oscillations of systemic blood pressure (BP) and cerebral blood flow velocities (CBFV). METHODS:Eight SAH patients underwent prospectively a median of 7 DCA assessments consisting of continuous measurements of BCFV and BP. Transfer function analysis was applied to calculate average phase shift (PS) in low (0.07-0.2 Hz) frequency range for each hemisphere as continuous measure of DCA. Lower PS indicated poorer regulatory response. DCI was defined as a 2-point decrease in Glasgow Coma Score and/or infarction on CT. RESULTS:Three subjects developed symptomatic vasospasm with median time-to-DCI of 9 days. DCI was significantly associated with lower PS over the entire recording period (Wald = 4.28; p = 0.039). Additionally, there was a significant change in PS over different recording periods after adjusting for DCI (Wald = 15.66; p = 0.001); particularly, a significantly lower mean PS day 3-5 after bleed (14.22 vs 27.51; p = 0.05). CONCLUSIONS:DCA might be useful for early detection of symptomatic vasospasm. A larger cohort study of SAH patients is currently underway.

COVID-19 is a severe infectious disease that has claimed >150,000 lives and infected millions in the United States thus far, especially the elderly population. Emerging evidence has shown the virus to cause hemorrhagic and immunologic responses, which impact all organs, including lungs, kidneys, and the brain, as well as extremities. SARS-CoV-2 also affects patients', families', and society's mental health at large. There is growing evidence of re-infection in some patients. The goal of this paper is to provide a comprehensive review of SARS-CoV-2-induced disease, its mechanism of infection, diagnostics, therapeutics, and treatment strategies, while also focusing on less attended aspects by previous studies, including nutritional support, psychological, and rehabilitation of the pandemic and its management. We performed a systematic review of >1,000 articles and included 425 references from online databases, including, PubMed, Google Scholar, and California Baptist University's library. COVID-19 patients go through acute respiratory distress syndrome, cytokine storm, acute hypercoagulable state, and autonomic dysfunction, which must be managed by a multidisciplinary team including nursing, nutrition, and rehabilitation. The elderly population and those who are suffering from Alzheimer's disease and dementia related illnesses seem to be at the higher risk. There are 28 vaccines under development, and new treatment strategies/protocols are being investigated. The future management for COVID-19 should include B-cell and T-cell immunotherapy in combination with emerging prophylaxis. The mental health and illness aspect of COVID-19 are among the most important side effects of this pandemic which requires a national plan for prevention, diagnosis and treatment.

Background: CANA slows progression of chronic kidney disease (CKD) in people with type 2 diabetes. CANA also induces a reversible acute decline in estimated glomerular filtration rate (eGFR), which is believed to be a hemodynamic effect. Predictors of the initial decline and its association with long-term eGFR trajectories and safety outcomes are unknown.
Method(s): This post hoc study of CREDENCE included 4289 patients with type 2 diabetes and CKD who had eGFR measured at both baseline and week 3. Participants were categorized by percentage decline in eGFR at week 3: greater than 10% decline; between 0 and 10% decline; and no decline. Baseline characteristics associated with acute eGFR drop >10% were evaluated using logistic regression. Long-term eGFR decline and safety outcomes were estimated in each eGFR decline category by linear mixed effects models and Cox regression after adjustment for laboratory measures and medication use.
Result(s): More participants in the CANA (956 [45%]) versus placebo (PBO) group (450 [21%]) had an acute eGFR decline >10% (p<0.001). A >30% decline occurred infrequently (89 [4%] with CANA and 39 [2%] with PBO; p<0.001). In the CANA but not in the PBO group, older age (OR CANA 1.17, 95% CI 1.05-1.31; per 10 years) and history of heart failure (OR CANA 0.77, 0.59-0.99) were associated with a higher and lower likelihood of an acute eGFR decline >10%, respectively (both p interaction<0.05). Following the initial eGFR change, long-term eGFR trajectories were similar across eGFR decline categories (all p>0.05). Safety profiles were also similar except when the drop unusually exceeded 30%, in which case adverse events and renal related adverse events occurred more frequently. Results were consistent in subgroup analysis by baseline eGFR (30-<45, 45-<60, and 60-<90 mL/min/1.73m²).
Conclusion(s): Although acute eGFR declines >10% occurred in nearly half of all patients following initiation of CANA, the benefit of CANA compared with PBO was observed regardless of the acute eGFR decline and safety profiles were similar

The presence of an extra copy of human chromosome 21 (Hsa21) leads to a constellation of phenotypic manifestations in Down syndrome (DS), including prominent effects on the brain and immune system. Intensive efforts to unravel the molecular mechanisms underlying these phenotypes may help developing effective therapies, both in DS and in the general population. Here we review recent progress in genetic and epigenetic analysis of trisomy 21 (Ts21). New mouse models of DS based on syntenic conservation of segments of the mouse and human chromosomes are starting to clarify the contributions of chromosomal subregions and orthologous genes to specific phenotypes in DS. The expression of genes on Hsa21 is regulated by epigenetic mechanisms, and with recent findings of highly recurrent gene-specific changes in DNA methylation patterns in brain and immune system cells with Ts21, the epigenomics of DS has become an active research area. Here we highlight the value of combining human studies with mouse models for defining DS critical genes and understanding the trans-acting effects of a simple chromosomal aneuploidy on genome-wide epigenetic patterning. These genetic and epigenetic studies are starting to uncover fundamental biological mechanisms, leading to insights that may soon become therapeutically relevant.