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Background: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a chronic condition affecting the elderly. It is characterized by a triad of symptoms and radiological findings. Glaucoma is the leading cause of irreversible blindness worldwide. Earlier studies have proposed that the rate of glaucoma is higher in iNPH patients, and of a possible link between ventriculoperitoneal shunt (VP) treatment and the development of glaucoma. Objectives: This study aimed to determine the prevalence of glaucoma among iNPH patients and assess the impact of VPs on glaucoma prevalence. Methods: A cohort study was conducted at Kuopio University Hospital (KUH), including 262 patients with a ventriculoperitoneal shunt. Clinical data were obtained from the Kuopio NPH Registry and medical records. Patients were grouped by iNPH status: iNPH (+) – probable/possible iNPH (n = 192), and iNPH (-) – other causes of hydrocephalus (congenital, secondary, obstructive) (n = 70). We conducted statistical analysis using the Independent Samples T-test, Fisher's exact test, and Pearson Chi-Square. We compared demographics, glaucoma prevalence, brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) as well as comorbidities for hypertension and diabetes medication. Age stratification assessed glaucoma prevalence in the full cohort. Results: Both iNPH (+) and iNPH (-) groups had comparable demographic and comorbidity profiles. The prevalence of glaucoma in the iNPH (+) group was 11.5% (n = 22) and 11.4% (n = 8) in the iNPH (-) group without a statistically significant difference (p = 1.000). Brain biopsies positive for Amyloid-β (Aβ) and hyperphosphorylated tau (HPτ) were similar. Conclusions: Neither shunted iNPH patients nor those with a comorbid condition other than iNPH showed a markedly higher prevalence of glaucoma. Instead, both groups exhibited age-related increases in glaucoma prevalence, similar to the trends observed in population-based studies. Our data does not suggest a correlation between VP shunts and an elevated rate of glaucoma. [ABSTRACT FROM AUTHOR]

Background: Association between visual field test indices and The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD-NB) is unknown. Idiopathic normal pressure hydrocephalus (iNPH) patients provide a unique set of patient data for analysis. Objective: To assess the reliability of visual field testing using the CERAD-NB in patients with iNPH and to investigate the association between visual field test results and cognitive function. Methods: 62 probable iNPH patients were subjected to comprehensive ophthalmological examination, ophthalmological optical coherence tomography imaging studies, visual field testing, and CERAD-NB. Based on visual field indices, the patients were divided into two groups: unreliable (n = 19) and reliable (n = 43). Independent T-test analysis was performed to examine the relationship between visual field test results and cognitive function. Pearson Chi-square test was used for non-continuous variables. Results: The unreliable group performed worse in CERAD-NB subtests compared to the reliable group. Statistically significant differences were observed in nine out of ten subtests, with only Clock Drawing showing no statistical significance. Pairwise comparison of the groups showed no statistical significance between amyloid-β (Aβ) biopsy, hyperphosphorylated tau biopsy, apolipoprotein E allele or the ophthalmological status of the patient. But there was a statistically significant difference in cerebrospinal fluid Aβ42 and age between the groups. Conclusions: Patients with unreliable visual field tests performed worse on CERAD-NB subtests. CERAD-NB subtests do not provide a specific cut-off value to refrain patients from visual field testing. Should patients with unreliable visual field tests be screened for cognitive impairment? [ABSTRACT FROM AUTHOR]

Aims/Purpose: Most ocular disease is managed at least in part by use of eye drops. Many of these eye drops require multiple doses per day, as well as good patient compliance to relieve patients from incapacitating symptoms. To address this treatment burden, a Silica Matrix long‐acting eye drop technology was developed to offer a once‐a‐day (QD) dosing schedule. The aim of this study was to evaluate safety and tolerability of QD repeated dosing of silica composite eye drop platform in healthy volunteers for 15 days. Methods: 24 healthy volunteers were recruited to a randomized, double blinded, placebo‐controlled phase 1 clinical trial for repeated, QD dosing of silica composite eye drops over 15 days. Half of the subjects received a demulcent containing silica composite eye drops and the other half received plain silica composite eye drops (i.e., placebo). A single drop was applied QD in the cul‐de‐sac of one eye, and safety and tolerability was assessed by a blinded Investigator, including examination of outer eye structures and anterior chamber as well as interblink interval and tear fluid break‐up time (t0, 6h, D2, D3, D7, D11 and D15), lens examination (microscopic), change in visual acuity (EDTRS) and intra‐ocular pressure (t0 and D15). Ocular discomfort was assessed by volunteer questionnaire at t0, 6h, D3, D7, D11 and D15. Results: At submission, 13 subjects have completed the study and 11 are still under investigation. No significant differences in tolerability were observed between treated and untreated eyes, with no relevant adverse events. Volunteer questionnaire results indicate that 71% regarded instillation discomfort as mild, 22% moderate and 7% had no symptoms. Discomfort lasted less than 1‐min in 99% of responses. Conclusions: The results indicate that silica composite eye drops are safe and well tolerated in healthy volunteers when applied QD. This forms a good basis for development of sustained release topical ocular products for delivery of pharmacologically active agents in eye diseases. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms underlying these two diseases remain elusive. Methods: Mice with different AD- and/or tauopathy-linked genetic backgrounds (APPswe/PS1dE9, Tau P301L and APPswe/PS1dE9/Tau P301L) were fed for 6 months with standard diet or typical Western diet (TWD). After behavioral and metabolic assessments of the mice, the effects of TWD on global gene expression as well as dystrophic neurite and microglia pathology were elucidated. Consequently, mechanistic aspects related to autophagy, cell survival, phagocytic uptake as well as Trem2/Dap12 signaling pathway, were assessed in microglia upon modulation of PI3K-Akt signaling. To evaluate whether the mouse model-derived results translate to human patients, the effects of diabetic phenotype on microglial pathology were assessed in cortical biopsies of idiopathic normal pressure hydrocephalus (iNPH) patients encompassing β-amyloid pathology. Results: TWD led to obesity and diabetic phenotype in all mice regardless of the genetic background. TWD also exacerbated memory and learning impairment in APPswe/PS1dE9 and Tau P301L mice. Gene co-expression network analysis revealed impaired microglial responses to AD-related pathologies in APPswe/PS1dE9 and APPswe/PS1dE9/Tau P301L mice upon TWD, pointing specifically towards aberrant microglial functionality due to altered downstream signaling of Trem2 and PI3K-Akt. Accordingly, fewer microglia, which did not show morphological changes, and increased number of dystrophic neurites around β-amyloid plaques were discovered in the hippocampus of TWD mice. Mechanistic studies in mouse microglia revealed that interference of PI3K-Akt signaling significantly decreased phagocytic uptake and proinflammatory response. Moreover, increased activity of Syk-kinase upon ligand-induced activation of Trem2/Dap12 signaling was detected. Finally, characterization of microglial pathology in cortical biopsies of iNPH patients revealed a significant decrease in the number of microglia per β-amyloid plaque in obese individuals with concomitant T2D as compared to both normal weight and obese individuals without T2D. Conclusions: Collectively, these results suggest that diabetic phenotype in mice and humans mechanistically associates with abnormally reduced microglial responses to β-amyloid pathology and further suggest that AD and T2D share overlapping pathomechanisms, likely involving altered immune function in the brain. [ABSTRACT FROM AUTHOR]