Association Between False Memories and Delusions in Alzheimer Disease

IMPORTANCE: Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. OBJECTIVE: To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. DESIGN, SETTING, AND PARTICIPANTS: Since the Alzheimer's Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. EXPOSURE: Enrollment in the ADNI. MAIN OUTCOMES AND MEASURES: The main outcomes included false recognition, measured with the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. RESULTS: Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P < .001), right hippocampal volume (0.94 [0.92-0.97], P < .001), left entorhinal cortex volume (0.94 [0.91-0.97], P < .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P < .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P < .001). There was no overlap between locations associated with false recognition and those associated with delusions. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis

Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease

Introduction: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. Methods: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. Results: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50–90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. Discussion: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease

Combining navigator and optical prospective motion correction for high-quality 500 μm resolution quantitative multi-parameter mapping at 7T

PURPOSE: High-resolution quantitative multi-parameter mapping shows promise for non-invasively characterizing human brain microstructure but is limited by physiological artifacts. We implemented corrections for rigid head movement and respiration-related B0-fluctuations and evaluated them in healthy volunteers and dementia patients. METHODS: Camera-based optical prospective motion correction (PMC) and FID navigator correction were implemented in a gradient and RF-spoiled multi-echo 3D gradient echo sequence for mapping proton density (PD), longitudinal relaxation rate (R1) and effective transverse relaxation rate (R2*). We studied their effectiveness separately and in concert in young volunteers and then evaluated the navigator correction (NAVcor) with PMC in a group of elderly volunteers and dementia patients. We used spatial homogeneity within white matter (WM) and gray matter (GM) and scan-rescan measures as quality metrics. RESULTS: NAVcor and PMC reduced artifacts and improved the homogeneity and reproducibility of parameter maps. In elderly participants, NAVcor improved scan-rescan reproducibility of parameter maps (coefficient of variation decreased by 14.7% and 11.9% within WM and GM respectively). Spurious inhomogeneities within WM were reduced more in the elderly than in the young cohort (by 9% vs. 2%). PMC increased regional GM/WM contrast and was especially important in the elderly cohort, which moved twice as much as the young cohort. We did not find a significant interaction between the two corrections. CONCLUSION: Navigator correction and PMC significantly improved the quality of PD, R1, and R2* maps, particularly in less compliant elderly volunteers and dementia patients

Effects of the visual environment on object localization in posterior cortical atrophy and typical Alzheimer's disease.

INTRODUCTION: Visual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease. METHODS: 15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit. RESULTS: Across both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50-90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none. DISCUSSION: Findings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease

Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints

Bayram, Cem/0000-0001-8717-4668;WOS: 000340277700020PubMed: 24939720In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubility of the drug and hydrophobic nature of PCL. However, when coloaded with TA, both drugs were released at higher amounts compared with their single forms. Smallest particle sizes were obtained in dual drug-loaded microspheres. In vitro cytotoxicity tests showed biocompatibility of microspheres. In vivo bioefficacy of these microspheres was also examined in adjuvant-induced arthritis model in rats. In vivo histological studies of control groups showed development of RA with high median lesion score (5.0). Compared with control and intra-articular free drug injections, microsphere treatment groups showed lower lesion scores and better healing outcomes in histological evaluations. Results suggest that a controlled delivery system of TA and RAL by a single injection in inflamed joints holds promise for healing and suppressing inflammation. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2396-2405, 2014Middle East Technical UniversityMiddle East Technical UniversityWe thank to Middle East Technical University for financially supporting the study

Sonographic Diagnosis Of Large-Cell Calcifying Sertoli Cell Tumor

Large-cell calcifying Sertoli cell tumor is a very rare neoplasm of the testis with less than 100 reported cases. It is associated with some genetic syndromes, and it has some features that help to distinguish benign and malign cases. An 11-year-old boy presented with testicular lesions in both testicles. He underwent right radical orchiectomy in another institution and was referred to our hospital for further treatment. The lesions were reported as large-cell calcifying Sertoli cell tumors in our institution. There were multiple hyperechoic lesions with calcifications in the left testis and lesions showed vascularization on Doppler. Sonographic features of these lesions were also suggestive of benign large-cell calcifying Sertoli cell tumor. The lesions were stabile during follow-up. The ultrasonographic appearance of large-cell calcifying Sertoli cell tumor is descriptive and, together with clinical findings, allows differential diagnosis. It can direct patient management, with a more conservative approach. We report a child with large-cell calcifying Sertoli cell tumor who could have been saved from extensive surgery, such as radical orchiectomy, if the tumor had been diagnosed correctly with sonography.PubMedWoSScopu

Longer anogenital distance in female fetus of diabetic and obese pregnant women

Objective: Previous studies revealed that prenatal exposure to androgen excess such as polycystic ovary syndrome (PCOS) is associated with offspring's anogenital distance (AGD) length, and AGD is a biomarker of intrauterine androgen exposure. This study aims to investigate a possible relationship of fetal AGD with maternal diabetes and obesity, and to evaluate whether AGD predicts the fetal androgen exposure related to diabetes and obesity in female fetus. This study is the first to focus on the relationship between offspring's AGD and maternal diabetes and obesity. Materials and methods: This is a prospective study investigating 218 pregnant women (125 in control group and 93 in study group). Fetal AGD was measured from the center of anus to the posterior convergence of the fourchette by ultrasound. Multivariate linear regression analysis was applied to assess the association of the fetal AGD length with maternal diabetes and obesity. Results: The control patients had significantly shorter fetal AGD (mean:10.7 mm, P < 0.001) compared to diabetic, obese and diabetic obese patients (mean: 12.6 mm, 12.8 mm and 12.9 mm, respectively). The results of regression analysis showed that both maternal diabetes and obesity were significantly correlated with longer AGD in female fetus. The results confirmed also that offspring's AGD measurement in utero by ultrasound is feasible and reliable. Conclusion: The study findings suggest that both maternal diabetes and obesity are associated with intrauterine androgenic milieu during pregnancy, and fetal AGD may be used as a biomarker to predict this effect. This may provide important advantages in terms of early detection of reproductive system abnormalities related to prenatal androgen exposure

Criteria sets for primary Sjogren's syndrome are not adequate for those presenting with extraglandular organ involvements as their dominant clinical features

Patients with primary Sjogren's syndrome (pSS) may go undiagnosed or be misclassified due to the insidious nature and wide spectrum of the disease. The available several classification criteria emphasize glandular findings. We aimed to analyze the efficiency of various classification criteria sets in patients diagnosed on the clinical basis by expert opinion and to compare those pSS patients who fulfilled these criteria with those who did not. This is a multicenter study in which 834 patients from 22 university-based rheumatology clinics are included. Diagnosis of pSS was made on the clinical basis by the expert opinion. In this study, we only interviewed patients once and collected available data from the medical records. The European criteria, American-European Consensus Group (AECG) and American College of Rheumatology (ACR) Sjogren's criteria were applied. Majority of the patients were women (F/M was 20/1). The median duration from the first pSS-related symptom to diagnosis was significantly shorter in men (2.5 +/- 2.3 vs 4.3 +/- 5.9 years) (p = 0 < 0.016). When the European, AECG and ACR Sjogren's criteria were applied, 666 patients (79.9%) satisfied at least one of them. In total, 539 patients (64.4%) satisfied the European, 439 (52.6%) satisfied the AECG, and 359 (43%) satisfied the ACR criteria. Among the entire group, 250 patients (29.9%) satisfied all and 168 (20.1%) met none of the criteria. The rates of extraglandular organ involvements were not different between patients who met at least one of the criteria sets and those who met none. There is an urgent need for the modification of the pSS criteria sets to prevent exclusion of patients with extraglandular involvements as the dominant clinical features