The Auditory Afferent Pathway as a Clinical Marker of Alzheimer's Disease.

Brain stem neural tracts and nuclei may be disturbed prior to observable neuronal atrophy in AD. In this perspective, we discuss the notion of functional deficits presenting prior to structural abnormalities in Alzheimer's disease (AD). Imaging of inferior colliculi using magnetic resonance spectroscopy (MRS) shows significant decrease in the neuronal markers, N acetyl aspartate/creatine ratio and increase in the glial marker myo-Inositol, in subjects with Mini-Mental State Examination scores greater than 24 and with no signs of atrophy in their MRI of the medial temporal lobe. Abnormalities in components of the auditory event-related potentials (ERPs) are described in cognitive impairment including AD. We observed a significant decrease in amplitude and increase in latency during the first 10 ms of auditory evoked potentials measured on electroencephalography (EEG) indicating slow auditory response of the brainstem. EEG spectral power recorded at the cortex is also associated with neural activity at the level of the inferior colliculi. We postulate that a functional examination of auditory afferent pathways, using non-invasive techniques, such as MRS, brain stem auditory evoked potentials (BAEPs) and ERPs may improve diagnostic accuracy of AD. Functional changes precede structural changes and it is important to further understand the relationship between biochemical and electrophysiological measures such as MRS, BAEPs and EEG.

The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases.

Nigella sativa (N. sativa) is an annual flowering plant that has been used as a traditional remedy for many centuries. The seed possesses a large variety of compounds with thymoquinone (TQ) considered its major but not sole bioactive constituent. Supercritical fluid extraction, geographical location, and oxidative status of N. sativa produces the highest yield of essential oil content including TQ. Thymoquinone is lipophilic, heat and light sensitive with low oral bioavailability and rapid elimination that have significantly inhibited its pharmacological development. Novel developments in nanoparticulate-based oral administration, nasal spray and transdermal delivery may allow the clinical development of N. sativa and TQ as therapeutic agents. Animal and human studies indicate a potential role of N. sativa seed oil and TQ for a diverse range of disease processes including hypertension, dyslipidaemia, type 2 diabetes mellitus, arthritis, asthma, bacterial and viral infections, neurological and dermatological disorders, as it belongs to the group of pan-assay interference compounds. This review outlines the pharmacological properties of N. sativa and TQ and their potential wide application for a large variety of human diseases. The paper will focus on recent studies of the anti-inflammatory and antiviral properties that make N. sativa and TQ promising therapeutic agents targeting contemporary inflammatory and infectious diseases including Covid 19.

Functional Outcomes at 90 Days in Octogenarians Undergoing Thrombectomy for Acute Ischemic Stroke: A Prospective Cohort Study and Meta-Analysis.

Background: Elderly patients account for 30% of acute ischemic stroke (AIS) but are under-represented in randomized controlled trials of endovascular thrombectomy (EVT). Meta-analysis of "real world" studies evaluating 90-day outcomes in elderly patients ≥80 years have been limited to small numbers undergoing EVT with older generation devices. Methods: A retrospective analysis of 181 prospectively collected patients who received EVT for anterior circulation AIS at an Australian center over 2.5-years. The study aims to determine (i) 90-day functional outcomes (modified Rankin Scale mRS 0-2) in patients ≥80 vs. <80 years, (ii) the interaction of prognostic factors and age and (iii) compare our data to those previously reported using a meta-analysis of outcomes in observational studies using second generation thrombectomy devices. Results: We analyzed 2,387 patients (≥80 years, n = 649; <80 years, n = 1,738) from 14 studies including our study (≥80 years, n = 71; <80 years, n = 110). Twenty-eight percent of our and 30% of the meta-analysis elderly cohort achieved good 90-day mRS compared to 55 and 52%, respectively of younger patients (p < 0.001). Twenty-seven percent of our and 26% of the meta-analysis elderly cohort died compared to 16% (p = 0.07) and 15% (p < 0.0001), respectively of younger patients. Baseline NIHSS≥16 correlated with poor prognosis in elderly (OR 16.4; 95% CI 4.49-59.91, p < 0.001) and younger (OR 8.73;95% CI 3.35-22.80, p < 0.001) patients. Prior rt-PA was associated with favorable outcome in younger (OR 2.90; 95%CI 1.29-6.52, p = 0.01) patients only. Conclusion: EVT has less favorable outcomes in elderly patients. However, results are better than outcomes in historical controls not treated with thrombectomy providing further support for EVT in the elderly.

Dementia with Lewy bodies in an elderly Greek male due to alpha-synuclein gene mutation.

We report the case of an elderly man of Greek background who presented with progressive cognitive decline and motor parkinsonism on a background of a strong family history of Parkinson's disease. Associated symptoms included visual hallucinations, excessive daytime drowsiness, recurrent falls, orthostatic hypotension and urinary incontinence. His major clinical symptoms and signs fulfilled consensus criteria for a clinical diagnosis of dementia with Lewy bodies. An alpha-synuclein gene mutation analysis for the G209A substitution was positive. We conclude that the alpha-synuclein (G209A) gene mutation genotype should be considered in the differential diagnosis of dementia with Lewy bodies, particularly in patients with European ancestry and a family history of Parkinson's disease.

A comparison of health-care costs involved in treating people with and without Parkinson's disease in Southern Sydney, New South Wales, Australia.

Twelve community-dwelling subjects with Parkinson's disease (PD) and 12 age-matched healthy controls completed a 3-month diary of health-care utilisation in Sydney, Australia. The mean age for the PD group was 71.3 years (SD 5.9, range 62-82 years) versus 73.2 years (SD 6.7, range 63-83 years) for the control group. The mean disease duration of the PD group was 6.8 years (SD 3.6, range 2-14 years). The median Hoehn and Yahr stage was 3 (range 1-3). The mean 3-month total (both related and 'unrelated' to PD) health-care cost for the PD group was significantly higher than that for the 'healthy' control group (1,755 Australian dollars, SD 1,201 versus 413 Australian dollars, SD 515, P=0.001). Medication was the most costly component for both groups (PD 636 Australian dollars, SD 226 versus controls 175 Australian dollars, SD 233, P<0.001) followed by general practitioner or specialist medical expenses (PD 564 Australian dollars, SD 670 versus controls 205 Australian dollars, SD 397, p=0.12) and allied health-care costs (PD 323 Australian dollars, SD 178 versus controls 21 Australian dollars, SD 43, p<0.001). In the PD subgroup, the health-care costs attributed to PD during the 3-month period were significantly higher than health-care costs 'unrelated' to PD (1,202 Australian dollars, SD 820 versus 553 Australian dollars, SD 591, p=0.03). On subgroup analysis, allied health-care costs (related to PD) achieved statistical significance (304 Australian dollars, SD 180 versus 19 Australian dollars, SD 19, p<0.0001), whereas medication and general practitioner or specialist costs did not. In conclusion, we found that the total direct health-care cost of PD for patients with Hoehn and Yahr stage 3 was four times that of age- and sex-matched 'healthy' controls. The estimated annual cost (7,020 Australian dollars per patient) in our patient cohort was comparable to that reported in the United States and Europe.