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Purpose: Intratumoral hypoxia in non-Hodgkin's Lymphoma (NHL) may interfere with chimeric antigen receptor T-cell (CAR-T) function. We conducted a single-center pilot study (clinicaltrials.gov ID NCT04409314) of [18F]fluoroazomycin arabinoside, a hypoxia-specific radiotracer abbreviated as [18F]FAZA, to assess the feasibility of this positron emission tomography (PET) imaging modality in this population. Methods: Patients with relapsed NHL being evaluated for CAR-T therapy received a one-time [18F]FAZA PET scan before pre-CAR-T lymphodepletion. A tumor to mediastinum (T/M) ratio of 1.2 or higher with regard to [18F]FAZA uptake was defined as positive for intratumoral hypoxia. We planned to enroll 30 patients with an interim futility analysis after 16 scans. Results: Of 16 scanned patients, 3 had no evidence of disease by standard [18F]fluorodeoxyglucose PET imaging before CAR-T therapy. Six patients (38%) had any [18F]FAZA uptake above background. Using a T/M cutoff of 1.20, only one patient (a 68-year-old male with relapsed diffuse large B-cell lymphoma) demonstrated intratumoral hypoxia in an extranodal chest wall lesion (T/M 1.35). Interestingly, of all 16 scanned patients, he was the only patient with progressive disease within 1 month of CAR-T therapy. However, because of our low overall proportion of positive scans, our study was stopped for futility. Conclusions: Our pilot study identified low-level [18F]FAZA uptake in a small number of patients with NHL receiving CAR-T therapy. The only patient who met our pre-specified threshold for intratumoral hypoxia was also the only patient with early CAR-T failure. Future plans include exploration of [18F]FAZA in a more selected patient population. [ABSTRACT FROM AUTHOR]

The Alzheimer's Questionnaire (AQ) is an informant-based screening tool with good diagnostic accuracy for Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). The aim of this study is to validate the AQ with AD-associated neuritic plaque (NP) and neurofibrillary tangle (NFT) pathology. Data from 205 prospectively followed autopsy cases clinically classified as AD (n = 90), aMCI (n = 42), or cognitively unimpaired (CU, n = 73) were used. Semi-quantitative measures of NP and NFT pathology were correlated with the AQ, Clinical Dementia Rating Sum of Boxes (CDR-SOB), and the Mini-Mental State Exam (MMSE). The AQ correlated significantly (p < 0.001) with NP load (r = 0.37) and NFT load (r = 0.57). The MMSE and CDR-SOB showed similar correlations with NP load (r = − 0.37, r = 0.35, respectively) and NFT load (r = − 0.58, r = 0.55, respectively). The AQ correlates well with NP and NFT pathology of AD, which provides additional confidence to clinicians using the AQ to screen for AD-related cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Cognitive screening is important for the oldest-old (age 90 +). This age group is the fastest growing and has the highest risk of dementia. However, norms and score equivalence for screening tests are lacking for this group. Aims: To provide norms and score equivalence for commonly used cognitive screening tests for the oldest-old. Methods: Data on 157 participants of the Center for Healthy Aging Longevity Study aged 90 + were analyzed. First, we derived norms for (1) subtests and cognitive domains of the in-person Montreal Cognitive Assessment having a maximum score of 30 (MoCA-30) and (2) the total MoCA-22 score, obtained from the in-person MoCA-30 by summing the subtests that do not require visual input to a maximum score of 22. These norms were derived from 124 participants with a Mini-Mental State Examination (MMSE) ≥ 27. Second, we derived score equivalences for MMSE to MoCA-30 and MoCA-22, and MoCA-30 to MoCA-22 using equipercentile equating method with log-linear smoothing, based on all 157 participants. Results: MoCA-22 total score norms are: mean = 18.3(standard deviation = 2.2). An MMSE score of 27 is equivalent to a MoCA-30 score of 22 and a MoCA-22 score of 16. Discussion and conclusions: Subtest, domain and MoCA-22 norms will aid in evaluation of the oldest-old who cannot complete the MoCA-30 or are tested over the phone. The equivalences of the three cognitive tests (MMSE, MoCA-30, MoCA-22) in the oldest-old will facilitate continuity of cognitive tracking of individuals tested with different tests over time and comparison of the studies that use different cognitive tests. [ABSTRACT FROM AUTHOR]

Purpose: Bevacizumab is an active anti-angiogenic agent in the treatment of recurrent glioblastoma. Temozolomide can prolong survival in patients with newly diagnosed glioblastoma. At recurrence, alternate dosing of temozolomide has shown to further deplete methyl-guanine-methyltransferase (MGMT) conferring added activity for patients who have progressed on the standard dosing regimen. In this study, bevacizumab plus biweekly temozolomide was evaluated for efficacy in adult patients with recurrent glioblastoma.Methods: Thirty patients with recurrent glioblastoma were treated with bevacizumab on (10 mg/kg i.v.) days 1 and 15 of a 28-day cycle combined with temozolomide (100 mg/m2) on days 1-5 and 15-19 on a 28-day cycle. Responses were assessed at week 4 and then every 8 weeks. MGMT status and quality of life measures were also assessed.Results: Overall response rate from diagnosis was 51 weeks, the 6-month progression-free survival was 52%, and median time to tumor progression was 5.5 months.Conclusion: Bevacizumab plus bi-weekly temozolomide was well tolerated and may be a salvage regimen to be considered in a subset of patients with recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Although, by age 40, individuals with Down syndrome (DS) develop amyloid-β (Aβ) plaques and tau-containing neurofibrillary tangles (NFTs) linked to cognitive impairment in Alzheimer's disease (AD), not all people with DS develop dementia. Whether Aβ plaques and NFTs are associated with individuals with DS with (DSD +) and without dementia (DSD −) is under-investigated. Here, we applied quantitative immunocytochemistry and fluorescent procedures to characterize NFT pathology using antibodies specific for tau phosphorylation (pS422, AT8), truncation (TauC3, MN423), and conformational (Alz50, MC1) epitopes, as well as Aβ and its precursor protein (APP) to frontal cortex (FC) and striatal tissue from DSD + to DSD − cases. Expression profiling of single pS422 labeled FC layer V and VI neurons was also determined using laser capture microdissection and custom-designed microarray analysis. Analysis revealed that cortical and striatal Aβ plaque burdens were similar in DSD + and DSD − cases. In both groups, most FC plaques were neuritic, while striatal plaques were diffuse. By contrast, FC AT8-positive NFTs and neuropil thread densities were significantly greater in DSD + compared to DSD −, while striatal NFT densities were similar between groups. FC pS422-positive and TauC3 NFT densities were significantly greater than Alz50-labeled NFTs in DSD + , but not DSD − cases. Putaminal, but not caudate pS422-positive NFT density, was significantly greater than TauC3-positive NFTs. In the FC, AT8 + pS422 + Alz50, TauC3 + pS422 + Alz50, pS422 + Alz50, and TauC3 + pS422 positive NFTs were more frequent in DSD + compared to DSD- cases. Single gene-array profiling of FC pS422 positive neurons revealed downregulation of 63 of a total of 864 transcripts related to Aβ/tau biology, glutamatergic, cholinergic, and monoaminergic metabolism, intracellular signaling, cell homeostasis, and cell death in DSD + compared DSD − cases. These observations suggest that abnormal tau aggregation plays a critical role in the development of dementia in DS. [ABSTRACT FROM AUTHOR]

Background: The Montreal cognitive assessment (MoCA) has become one of the most widely used cognitive screening instruments since its initial publication. To date, only a handful of studies have explored longitudinal characteristics of the MoCA.Aim: The aim of this study is to characterize the trajectory of MoCA performance across a broad age continuum of older adults.Methods: Data from 467 cognitively normal participants were used in this analysis. The sample was grouped into four strata based on the participants’ age at baseline (60-69, 70-79, 80-89, and 90-99). Mixed model repeated measures (MMRM) analysis and mixed-effects spline models were used to characterize the trajectory of MoCA scores in each age stratum and in the entire sample. Intrasubject standard deviation (ISD) was used to characterize the natural variability of individual MoCA performance over time.Results: The ISD values for each of the age strata indicated that year-to-year individual variation on the MoCA ranged from zero to three points. MMRM analysis showed that the 60-69 stratum remained relatively stable over time while the 70-79 and 80-89 strata both showed notable decline relative to baseline performance. The mixed-effects spline model showed that MoCA performance declines linearly across the older adult age span.Discussion: Among cognitively normal older adults MoCA performance remains relatively stable over time, however across the older adult age-span MoCA performance declines in a linear fashion. These results will help clinicians better understand the normal course of MoCA change in older adults while researchers may use these results to inform sample size estimates for intervention studies.Conclusion: This study provides an enhanced view of the MoCA’s intraindividual trajectory in normal elderly aged 60 and older. [ABSTRACT FROM AUTHOR]

The aim of the study is to telemedically assess the prevalence of simple optic nerve atrophy and retinal arteriolar anomalies in subjects who have had a minor stroke or TIA within 14 days, and to compare these results with an age-matched control group. By using a mobile examination unit, retinal photographs were taken with a 45° non-mydriatic colour fundus camera (KOWA NM-45, non-mydriatic-alpha) in patients who had suffered from a minor stroke or TIA within 14 days of the time of the examination. Retinal photographs were focused on the optic nerve head region. Pupils were not dilated. The documented medical history and the retinal images were stored on a server using browser independent web-based software running on PCs, tablets and smartphones. After completing the upload of the medical interview and the retinal images into the electronic patient chart, all retinal images were evaluated via telemedicine by an experienced senior consultant ophthalmologist. Age-matched normotensive, non-diabetic subjects (aged 40-89 years) who reported no systemic or ocular diseases were used as the control group. Both study groups were divided into five decades of life (40-49; 50-59; 60-69; 70-79; 80-89 years). We calculated the prevalences and the ratios of prevalences of optic nerve atrophy and retinal arteriolar anomalies between the stroke and the control group per decades of life. 139 minor stroke or TIA subjects (aged 40-89 years) and 1611 age-matched control subjects were examined. In the stroke group, we found significantly increased prevalences of optic nerve atrophy and retinal arteriolar anomalies throughout the 5th-8th decade of life when compared to age-matched controls. The prevalence of optic nerve atrophy in stroke subjects outranged the prevalence in the controls depending on age-class by a factor of 3-21. Simple optic nerve atrophy is frequent in patients who have suffered from an ischemic stroke or TIA, and it seems to indicate vascular damage, indicating the necessity for telemedically assisted assessment of the optic nerve. [ABSTRACT FROM AUTHOR]

The purpose of this article is to describe the Longevity Study: Learning From Our Elders, a research program on healthy aging that began in 2007 at the Center for Healthy Aging at Banner Sun Health Research Institute. As of June 2015, 1139 participants (age range of 50-110 years) completed baseline assessments with the majority living in the Sun Cities retirement communities northwest of Phoenix, Arizona but expanding throughout the state. The registry includes over 830 currently active participants with 450 aged 80 years and older, 188 aged 90 and older, and 27 centenarians. Data from in-person interviews at the Center for Healthy Aging in Sun City or in the participants' residences which includes sociodemographic, medical, cognitive, physical and psychosocial variables have been collected since the study's inception. This paper outlines some of the key demographic and clinical characteristics of the Longevity Study, its progress, and future directions. It also reflects on how exceptional aging individuals function psychosocially, cognitively and physically, particularly among individuals aged 85 and older. [ABSTRACT FROM AUTHOR]

Background: Previous studies investigating the relationship between sleep duration and cognitive function in older adults have suggested that longer sleep durations are associated with decreased cognitive performance. Aim: The intent of this study is to determine if performance on the Montreal Cognitive Assessment (MoCA) and the Mini Mental State Exam (MMSE) is associated with self-reported sleep duration in older adults. Methods: Data from 189 cognitively normal older adults aged 75 and older (mean age 89.29 ± 7.62) and free of severe depression were used for this analysis. Individuals were grouped based on their self-reported hours of sleep (short duration = <7, normal duration = 7, >9, and long duration = ≥9). The Kruskal-Wallis test was used to discern group differences on the MoCA scores, while multinomial logistic regression was used to assess the association between MoCA and MMSE scores and sleep group. Results: The long duration group had significantly lower MoCA scores than the normal duration group ( p = 0.02). The short duration group was not significantly different from the normal duration group ( p = 0.33). Individuals in the short duration group were more likely to have higher MoCA scores than those in long duration group after adjusting for age, gender, and presence of depressive symptoms [OR 0.86, 95 % CI (0.76, 0.98), p = 0.02]. Conclusion: The results of this study suggest that in a group of non-demented, very old subjects, self-reported sleep duration of nine or more hours is associated with decreased cognitive performance on the MoCA in older adults, even after accounting for age, gender, and presence of depressive symptoms. [ABSTRACT FROM AUTHOR]