Quality of life (QOL) and cognitive status among irradiated brain tumor survivors treated with donepezil or placebo.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2051-2051
Author(s):  
Doug Case ◽  
Michelle Joy Naughton ◽  
Volker W. Stieber ◽  
Gerald K. Bayer ◽  
Paul A. Bilodeau ◽  
...  

2051 Background: Cognitive problems after cancer therapy can decrease QOL. This phase III randomized trial tested the effect of donepezil (5-10 mg daily for 24 weeks) on cognition and QOL in brain cancer patients. Methods: Between 2/2008-12/2011, 198 (99 placebo; 99 donepezil) adult primary and metastatic brain tumor survivors > 6 months post radiation (> 30 Gy) were recruited at 24 sites affiliated with the Wake Forest CCOP Research Base, 3 CTSU sites, and M.D. Anderson. Outcomes were assessed at baseline, 12 and 24 weeks. Regression analyses examined the association of demographics, fatigue (FACIT-Fatigue), and a cognitive performance composite score (CC) (comprised of the Controlled Oral Word Association Test, Hopkins Verbal Learning Test-Revised, Digit Span Test, Trail Making Test A&B, Rey-Osterreith Complex Figure-modified, Grooved Pegboard) on QOL, measured by the FACT-Brain (FACT-Br) total score. Results: Participants had a median age of 55, were predominantly female (54%) and non-Hispanic White (91%), with a median time from diagnosis of 38 months. Study completion was 74%. At 12 and 24 weeks, treatment had no significant effect on QOL, unadjusted and adjusted for race/ethnicity, age, sex, fatigue, baseline FACT-Br, and baseline CC. However, for those below the median on the baseline FACT-Br subscale (i.e., greater cognitive symptoms), donepezil was associated with higher (better) post-tx FACT-Br total scores (p =0.004), unadjusted for covariates. After adjustment for covariates, donepezil was borderline significantly associated with higher post-tx QOL (p=0.052). Improvement in QOL was associated with being female (p=0.017) and less baseline fatigue (p=0.005). For participants with baseline FACT-Br subscale scores above the median, only lower baseline FACT-Br total scores (p=0.015) were significantly related to greater improvements in FACT-Br. Donepezil treatment was not significant (p=0.48). Conclusions: The impact of donepezil on QOL was greater in survivors with more cognitive symptoms at baseline, although the results were borderline significant. Fatigue continued to be a major factor in lower QOL. Other interventions to better manage survivors’ symptoms are needed. Clinical trial information: NCT00369785.

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
Jeffrey Weinberg ◽  
Mary Frances McAleer ◽  
Hussein Tawbi ◽  
Frederick Lang

Abstract BACKGROUND Resection (R) followed by single or multi-fraction stereotactic radiosurgery (SRS) lowers resection bed recurrence compared to R alone. Nevertheless for larger brain metastasis (>2.5 cm) 12-month recurrence rates after R+SRS can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy (CTBT) device (GammaTile, GT Medical Technologies, Tempe AZ) utilizing Cs-131 was developed, hypothesizing that immediate adjuvant radiotherapy (RT) and/or RT dose intensification could improve outcomes. The device received FDA clearance for this indication, based on a single-arm pre-commercial study and in early commercial use due to the excellent safety and local control of R+CTBT. It is hypothesized that R+CTBT will increase the time to post-resection-recurrence, while prolonging survival and reducing the impact on functional and neurocognitive status compared to R+SRS. STUDY DESIGN Multicenter, randomized, comparison trial. Patients with resectable, previously untreated “index” brain metastases measuring >2.5–5 cm and 0–3 other tumors will be preoperatively randomized 1:1 to undergo either R+ SRS or R+CTBT to the index lesion; unresected tumors in both groups will receive SRS. Planned sample size is 160 from ~5 sites; accrual to start in Q3-2020. Primary endpoint is surgical bed-recurrence free survival. Secondary endpoints include overall survival, quality of life (Functional Assessment of Cancer Therapy-Brain, Linear Analog Self-Assessment), neurocognition (Hopkins Verbal Learning Test, Trail Making Tests, Mini-Mental Status Exam, Controlled Oral Word Association), functional decline (Karnofsky Performance Scale, Barthel-ADL), and adverse events. Follow-up will be at 1,3,6,9, and 12 months, then q 6 months through 5 years. CONCLUSIONS This will be the first randomized trial comparing R+SRS versus R+CTBT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures will be captured to elucidate the potential risks and benefits of these two differing approaches for patients with metastatic brain tumors.


2019 ◽  
Vol 11 ◽  
pp. 117957351988404
Author(s):  
Stijn Denissen ◽  
Alexander De Cock ◽  
Tom Meurrens ◽  
Luc Vleugels ◽  
Ann Van Remoortel ◽  
...  

Background: Cognitive dysfunction is a frequent manifestation of multiple sclerosis (MS) but its effect on locomotor rehabilitation is unknown. Objective: To study the impact of cognitive impairment on locomotor rehabilitation outcome in people with MS. Methods: We performed a retrospective analysis involving ambulatory patients with MS who were admitted for intensive, inpatient, multidisciplinary rehabilitation at the National Multiple Sclerosis Center of Melsbroek between the years 2012 and 2017. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was used to determine the cognitive status of subjects as either impaired (COG–) or preserved (COG+). Locomotor outcome was compared between groups with the difference in 6-minute walk test (6MWT) measured at admission and discharge (Δ6MWT). In addition, individual test scores of the BRB-N for attention (Paced Auditory Serial Addition Test 2” and 3”), visuospatial learning/memory (7/24 Spatial Recall Test), verbal learning/memory (Selective Reminding Test) and verbal fluency (Controlled Oral Word Association Test) were correlated to the Δ6MWT. Results: A total of 318 complete and unique records were identified. Both groups showed a significant within-group Δ6MWT during hospitalization (COG+: 47.51 m; COG–: 40.97 m; P < .01). In contrast, Δ6MWT values were comparable between groups. The odds of achieving a minimal clinical important difference on the 6MWT did not differ significantly between both groups. Only attention/concentration was significantly correlated with Δ6MWT (r = 0.16, P = .013). Conclusion: Cognitive impairment based on BRB-N results appears not to impede locomotor rehabilitation in ambulatory patients with MS. Attentional deficits are correlated to the extent of locomotor rehabilitation, suggesting the presence of a subtle effect of cognition.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2006-2006 ◽  
Author(s):  
Stephen R. Rapp ◽  
Doug Case ◽  
Ann Peiffer ◽  
Michelle Joy Naughton ◽  
Volker W. Stieber ◽  
...  

2006 Background: This RCT assessed the effect of 24 weeks of 5-10 mg per day of donepezil, an acetyl cholinesterase inhibitor, on cognitive functioning (primary endpoint) and fatigue, mood and QOL in long-term brain tumor survivors following partial or whole-brain irradiation. Cognitive results are reported herein. Methods: From 2/08-12/11,198 adult primary and metastatic brain tumor survivors > 6 months post radiation treatment (>30 Gray) recruited at 24 sites affiliated with the Wake Forest Community Clinical Oncology Program Research Base, 3 CTSU sites and M.D. Anderson Cancer Center were randomly assigned to receive donepezil (n=99) or placebo (n=99). Cognitive function was assessed at baseline, 12 and 24 weeks with Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure, Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard. A Cognitive Composite (CC) score was the primary outcome. Results: The sample was 91% White, 54% female, and median age was 55 yrs. 66% had primary tumors, 27% brain metastases and 8% PCI. Median time since diagnosis: 38 mos. 95% had 0-1 ECOG performance status scores. 74% completed the study. CC score improved significantly by 24 weeks in both arms (p < .01); however, there was not a statistically significant difference between groups (p = .57). Donepezil group performed better than placebo on HVLT Recognition (p = .03) and Discrimination (p = .01) and GP-Dominant Hand (p = 0.02). Significant interactions were found between treatment arm and baseline cognitive scores for: CC (p = .01), HVLT Immed. Recall (p = .03), HVLT %Savings (p < .01), Digit Span Forward (p = .01), ROCF Copy (p = .03), TMT-B (p = .05) and GP-Dominant (p < .01). In all cases, the benefit of donepezil, relative to placebo, was greater for those with worse baseline scores. Conclusions: Long-term brain tumor survivors treated with brain irradiation who have cognitive impairment can benefit from 5-10mg of donepezil for 24 weeks. Improvements in verbal memory, working memory, visuo- and psychomotor performance and executive functioning were observed in this group. (Study supported by NIH/NINR grant 5R01NR009675-04, NIH/NCI grant 2 U10 CA 81851-09-13 and Eisai, Inc.) Clinical trial information: NCT00369785.


2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv3-iv4
Author(s):  
Najmus Iqbal ◽  
Tara Daisley-Devoy ◽  
Michelle Smalley ◽  
Anne Johnson ◽  
John Staffurth ◽  
...  

Abstract Cognitive impairment at diagnosis is prevalent in patients with brain metastases (BM). Neurocognitive function (NCF) decline following radiotherapy is well described in this patient cohort, but the impact of baseline NCF on clinical outcome and survival is less well understood. In this study we describe NCF in patients at baseline before undergoing stereotactic radiosurgery without whole brain radiotherapy and explore its impact on overall survival and explore possible causative factors. Baseline NCF data was collected in patients with 1–3 BM and WHO performance status 0–2. Patients underwent NCF assessments according to the RANO group and included Hopkin’s verbal learning test, controlled oral word association test, trail making test A and B and digit span. We collected quality of life (QoL) data using EORTC QLQ30/BN20 questionnaires and recorded functional assessment of cancer therapy scores. 31 patients underwent neurocognitive testing with mean age of 65 years and median overall survival was 10 months. 21 patients had a single metastasis. The most common primary site was lung (12) followed by melanoma (7). 64% of patients exhibited impaired NCF at baseline in at least 1 domain with a Z-score of >1 and this was associated with lower overall survival. Other factors associated with lower overall survival were presence of seizures, steroid use and larger tumour volume. In this study impaired NCF at baseline was associated with lower overall survival. Intracranial disease burden and the presence of seizures were also associated with worse NCF and worse survival indicating that these may be important causative factors to consider.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2004-2004 ◽  
Author(s):  
Jeffrey Scott Wefel ◽  
Stephanie L. Pugh ◽  
Terri S. Armstrong ◽  
Mark R. Gilbert ◽  
Minhee Won ◽  
...  

2004 Background: RTOG 0825 evaluated overall survival (OS) and progression-free survival (PFS) differences in patients with newly diagnosed GBM treated with standard chemoradiation, maintenance temozolomide and placebo (Arm 1) or bevacizumab (Arm 2). While OS was equivalent, PFS was longer in Arm 2. Longitudinal NCF testing was performed to evaluate clinical benefit. Methods: NCF was evaluatedat baseline and while on study and progression free with the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT) and Controlled Oral Word Association (COWA). Change in NCF from baseline was categorized using the reliable change index. Differences between treatment arms were compared at follow-up evaluations. Additionally, baseline (B) and early changes (EC) (B to week 10) in NCF were examined as prognostic factors. Results: 542 patients consented and 507 randomized patients participated, with test completion rates at weeks 0 (B), 10, 22, and 34 of 94-97, 69-73, 59-64, and 53-58%, respectively. Mean test performance at B was equivalent between arms and ranged from -0.8 to -4.8 SDs below healthy population norms with global NCF on a composite variable at -2.0 SDs. There were no statistically significant between arm differences in frequency of improvement through week 34. Decline on COWA (verbal measure of executive function) at week 34 relative to baseline was more common (16.1 vs 5.7%) in patients in Arm 1 (p<0.05); whereas, there were trends for more decline in Arm 2 on a visuomotor measure of executive function (TMT B, p< 0.06; 22.2 vs 35.4%). B performance and EC in global NCF, memory, executive function and processing speed were prognostic for OS. At B, global NCF was prognostic for PFS. EC in global NCF, memory and executive function were prognostic for PFS. Conclusions: There was a statistically significant difference in the frequency of decline on a verbal test of executive function at week 34 favoring Arm 2. However, this was not found at earlier time points and was not found on a visuomotor test of executive function. B and EC in NCF were prognostic for OS and PFS. Longitudinal modeling is ongoing to further evaluate the impact of treatment on patients’ NCF. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCI-2009-01670.


2021 ◽  
Vol 27 (6) ◽  
pp. 570-580
Author(s):  
Ashley M. Schnakenberg Martin ◽  
Deepak Cyril D’Souza ◽  
Sharlene D. Newman ◽  
William P. Hetrick ◽  
Brian F. O’Donnell

AbstractObjectives:Preclinical and clinical studies suggest that males and females may be differentially affected by cannabis use. This study evaluated the interaction of cannabis use and biological sex on cognition, and the association between observed cognitive deficits and features of cannabis use.Methods:Cognitive measures were assessed in those with regular, ongoing, cannabis use (N = 40; 22 female) and non-using peers (N = 40; 23 female). Intelligence, psychomotor speed, and verbal working memory were measured with the Wechsler Abbreviated Scale of Intelligence, Digit Symbol Test, and Digit Span and Hopkins Verbal Learning Test, respectively. Associations between cognitive measures and cannabis use features (e.g., lifetime cannabis use, age of initiation, time since last use of cannabis, recent high-concentration tetrahydrocannabinoid exposure) were also evaluated.Results:No main effects of group were observed across measures. Significant interactions between group and biological sex were observed on measures of intelligence, psychomotor speed, and verbal learning, with greatest group differences observed between males with and without regular cannabis use. Psychomotor performance was negatively correlated with lifetime cannabis exposure. Female and male cannabis use groups did not differ in features of cannabis use.Conclusions:Findings suggest that biological sex influences the relationship between cannabis and cognition, with males potentially being more vulnerable to the neurocognitive deficits related to cannabis use.


2018 ◽  
Vol 75 (3) ◽  
pp. 574-580 ◽  
Author(s):  
Nicole M Armstrong ◽  
Yang An ◽  
Luigi Ferrucci ◽  
Jennifer A Deal ◽  
Frank R Lin ◽  
...  

Abstract Background Hearing impairment (HI) could be a risk factor for cognitive decline, but cognition could plausibly also affect psychoacoustic assessment of hearing with audiometry. We examined the temporal sequence of hearing and cognitive function among nondemented, community-dwelling older adults. Methods Hearing and cognition were assessed between 2012 and 2015 and 2 years thereafter in 313 nondemented participants aged ≥60 years in the Baltimore Longitudinal Study of Aging. Poorer hearing was defined by pure-tone average of 0.5–4 kHz tones in the better-hearing ear. Cognitive measures with either visual or auditory inputs were Trail-making Test Part B; Digit Symbol Substitution Test; California Verbal Learning Test immediate recall, short delay, and long delay; Digit Span Forward/Backward; Benton Visual Retention Test; and Mini-Mental State Examination. We used linear regression models for cross-sectional associations at each timepoint and autoregressive, cross-lagged models to evaluate whether baseline hearing impairment (Time 1) predicted cognitive performance 2 years after baseline (Time 2) and vice versa. Results Cross-sectionally, there were no associations between poorer hearing and cognitive performance. Longitudinally, poorer hearing was associated with declines in California Verbal Learning Test immediate (β = −0.073, SE = 0.032, p = .024), short-delayed (β = −0.134, SE = 0.043, p = .002), long-delayed (β = −0.080, SE = 0.032, p = .012) recall, and Digit Span Forward (β = −0.074, SE = 0.029, p = .011).) from Time 1 to Time 2. Cognitive performance at Time 1 did not predict change in hearing status at Time 2. Conclusions Audiometric hearing impairment predicted short-term cognitive declines in both California Verbal Learning Test and auditory stimuli for attention.


2020 ◽  
Vol 35 (6) ◽  
pp. 1018-1018
Author(s):  
Arzuyan A ◽  
Mathew A ◽  
Rosenblatt A ◽  
Gracian E ◽  
Osmon D

Abstract Objective The Hopkins Verbal Learning Test–Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) are memory tests with embedded measures of performance validity (Recognition Discrimination [RD] and Discrimination Index [DI], respectively). We evaluated whether cognitive ability and age influenced embedded measures of effort. Methods Participants included 30 young adults (YA) and 29 older adults (dichotomized into unimpaired [OAu] and impaired [OAi]). Participants completed a medication management ability assessment (MMAA), daily memory lapses survey (DM), digit span, and the Transverse Patterning (TP) and Reversal Learning (RL) computerized tests. Two Repeated-Measures MANOVAs were conducted to determine if Passing PVT and Age/Cognitive Ability influenced performance. An ROC analysis was conducted for HVLT-RD and BVMT-DI to determine pass/fail, and false positives/negatives on embedded measures. Results Those in the YA group who failed RDS (YA-fail), performed better than OAi-fail and OAi-pass groups on RT Errors (p &lt; .0001). On TP Errors, the YA group differed from all four OA groups (p &lt; .0001). On MMAA a significant difference was observed between OAi-fail and all other groups (p &lt; .001). On RD, YA groups differed from both OAi groups (p = .0008). On DI, the YA groups differed from the OAi-fail group (p = .002). A logistic regression classified 43/57 participants successfully into the three cognitive groups using the six predictors (χ2 = 55.73, p &lt; .0001, R2 = .468). RT Errors and TP were significant (Likelihood χ2 = 7.25, p = .027). Conclusion HVLT-RD failed to detect validity for OAi, as did BVMT-DI for YA and OAu. Instead, impairment effects are seen on HVLT-RD and BVMT-DI where YA groups differed from some combination of both/one of the OA groups.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yaqin Zhao ◽  
Wenhuan Xiao ◽  
Kuanyu Chen ◽  
Qiongqiong Zhan ◽  
Fei Ye ◽  
...  

Abstract Background Accumulating evidence suggests that serum vascular endothelial growth factor (VEGF) in many neurobiological processes potentially contributes to the pathophysiology of psychiatric disorders, particularly cognitive decline. The purpose of this study was to explore the differences in neurocognition, social cognition and VEGF among remitted first-episode schizophrenic patients, non-remitters and normal control subjects. Moreover, we investigated the association between serum VEGF levels and cognitive functions. Method 65 remission (RS) and 45 nonremission patients (NRS) after first-episode schizophrenia, as well as 58 healthy controls (HC) were enrolled in this study. Social cognition was assessed using the Chinese Facial Emotion Test (CFET); neurocognition was measured with a test battery consisting of Hopkins Verbal Learning Test-Revised, Verbal Fluency Test, Trail Making Tests, Digit Span Tests (DST) and Stroop Tests. Blood samples were collected for VEGF measurements. Data was analyzed with SPSS 22.0 (Chicago, IL, USA). Results On nearly all neurocognitive tests (except for DST), RS performed significantly worse than HC but better than NRS (P < 0.05). NRS, but not RS, exhibited markedly poorer social cognition than HC (except for Happiness and Surprise subscales of the CFET) (P < 0.05). VEGF levels showed a gradient change among three groups (HC > RS > NRS). Conclusion Compared to HC, RS demonstrated poorer neurocognitive but intact social cognition functioning. These results indicate that VEGF levels decreased gradually with the severity of cognitive impairment in schizophrenia. VEGF may be involved in the pathological mechanism of cognitive performance in RS.


2020 ◽  
Vol 35 ◽  
pp. 153331751989672 ◽  
Author(s):  
Hong Wang ◽  
Xiangrong Shi ◽  
Hannah Schenck ◽  
James R. Hall ◽  
Sarah E. Ross ◽  
...  

Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown. This pilot study examined IHT’s safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI). Seven patients with aMCI (age 69 ± 3 years) alternately breathed 10% O2 and room-air, each 5 minutes, for 8 cycles/session, 3 sessions/wk for 8 weeks. The patients’ resting arterial pressures fell by 5 to 7 mm Hg ( P < .05) and cerebral tissue oxygenation increased ( P < .05) following IHT. Intermittent hypoxia training enhanced hypoxemia-induced cerebral vasodilation ( P < .05) and improved mini-mental state examination and digit span scores from 25.7 ± 0.4 to 27.7 ± 0.6 ( P = .038) and from 24.7 ± 1.2 to 26.1 ± 1.3 ( P = .047), respectively. California verbal learning test score tended to increase ( P = .102), but trail making test-B and controlled oral word association test scores were unchanged. Adaptation to moderate IHT may enhance cerebral oxygenation and hypoxia-induced cerebrovasodilation while improving short-term memory and attention in elderly patients with aMCI.


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