The wake- and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimers disease.

BACKGROUND: Sleep-wake dysfunction is an early and common event in Alzheimer's disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic neurons (OrxN) and sleep-promoting melanin-concentrating hormone or MCHergic neurons (MCHN). These neurons share close anatomical proximity with functional reciprocity. This study investigated LHA OrxN and MCHN loss patterns in AD individuals. Understanding the degeneration pattern of these neurons will be instrumental in designing potential therapeutics to slow down the disease progression and remediate the sleep-wake dysfunction in AD. METHODS: Postmortem human brain tissue from donors with AD (across progressive stages) and controls were examined using unbiased stereology. Formalin-fixed, celloidin-embedded hypothalamic sections were stained with Orx-A/MCH, p-tau (CP13), and counterstained with gallocyanin. Orx or MCH-positive neurons with or without CP13 inclusions and gallocyanin-stained neurons were considered for stereology counting. Additionally, we extracted RNA from the LHA using conventional techniques. We used customized Neuropathology and Glia nCounter (Nanostring) panels to study gene expression. Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when the p-value was <.05. RESULTS: We observed a progressive decline in OrxN alongside a relative preservation of MCHN. OrxN decreased by 58% (p=0.03) by Braak stages (BB) 1-2 and further declined to 81% (p=0.03) by BB 5-6. Conversely, MCHN demonstrated a non-statistical significant decline (27%, p=0.1088) by BB 6. We observed a progressive increase in differentially expressed genes (DEGs), starting with glial profile changes in BB2. While OrxN loss was observed, Orx-related genes showed upregulation in BB 3-4 compared to BB 0-1. GO and KEGG terms related to neuroinflammatory pathways were mainly enriched. CONCLUSIONS: To date, OrxN loss in the LHA represents the first neuronal population to die preceding the loss of LC neurons. Conversely, MCHN shows resilience to AD p-tau accumulation across Braak stages. The initial loss of OrxN correlates with specific neuroinflammation, glial profile changes, and an overexpression of HCRT, possibly due to hyperexcitation following compensation mechanisms. Interventions preventing OrxN loss and inhibiting p-tau accumulation in the LHA could prevent neuronal loss in AD and, perhaps, the progression of the disease.

Tongue forces and handgrip strength in normal individuals: association with swallowing

OBJECTIVES: To describe and correlate tongue force and grip strength measures and to verify the association of these measures with water swallowing in different age groups. METHOD: Tongue force was evaluated using the Iowa Oral Performance Instrument and grip strength using the Hand Grip in 90 normal individuals, who were divided into three groups: young (18-39 years old), adult (40-59 years old) and elderly (above 60 years old) individuals. The time and number of swallows required for the continuous ingestion of 200 ml of water were also measured. RESULTS: A reduction in tongue force and grip strength, as well as an increase in the time required to drink 200 ml of water, were observed with increasing participant age. There was no difference in the number of swallows among the three groups. A correlation was observed between reductions in tongue force and grip strength in the groups of young and elderly individuals. CONCLUSION: There were differences in the measures of tongue force in young, adult and elderly individuals. Greater variations within these differences were observed when repeated movements were performed; in addition, a decrease in strength was associated with an increase in age. The decrease in tongue force among the elderly was offset by the increase in time needed to swallow the liquid. There was an association between the measures of tongue force and grip strength in the different age groups. The results of this study can be applied clinically and may act as a basis for guidelines in healthy or vulnerable elderly populations. .

Correlation between intra-abdominal pressure and pulmonary volumes after superior and inferior abdominal surgery

OBJECTIVE: Patients undergoing abdominal surgery are at risk for pulmonary complications. The principal cause of postoperative pulmonary complications is a significant reduction in pulmonary volumes (FEV1 and FVC) to approximately 65-70% of the predicted value. Another frequent occurrence after abdominal surgery is increased intra-abdominal pressure. The aim of this study was to correlate changes in pulmonary volumes with the values of intra-abdominal pressure after abdominal surgery, according to the surgical incision in the abdomen (superior or inferior). METHODS: We prospectively evaluated 60 patients who underwent elective open abdominal surgery with a surgical time greater than 240 minutes. Patients were evaluated before surgery and on the 3rd postoperative day. Spirometry was assessed by maximal respiratory maneuvers and flow-volume curves. Intra-abdominal pressure was measured in the postoperative period using the bladder technique. RESULTS: The mean age of the patients was 56±13 years, and 41.6% 25 were female; 50 patients (83.3%) had malignant disease. The patients were divided into two groups according to the surgical incision (superior or inferior). The lung volumes in the preoperative period showed no abnormalities. After surgery, there was a significant reduction in both FEV1 (1.6±0.6 L) and FVC (2.0±0.7 L) with maintenance of FEV1/FVC of 0.8±0.2 in both groups. The maximum intra-abdominal pressure values were similar (p = 0.59) for the two groups. There was no association between pulmonary volumes and intra-abdominal pressure measured in any of the groups analyzed. CONCLUSIONS: Our results show that superior and inferior abdominal surgery determines hypoventilation, unrelated to increased intra-abdominal pressure. Patients at high risk of pulmonary complications should receive respiratory care even if undergoing inferior abdominal surgery. .