Objective
Patients with breast cancer face cognitive impairment that affects their quality of life; partially attributable to treatment. Our aim was to detail the prevalence and change of cognitive ...impairment during the course of treatment. We also investigated the effect of therapy (chemotherapy CT) vs. radiotherapy and/or endocrine therapy vs. healthy controls).
Methods
This article reviews longitudinal cohort studies published to date in Medline and Embase that (i) assess cognition before and after therapy, (ii) report prevalence cognitive impairment or change, and (iii) use standardized and valid neuropsychological tests. We used the original authors' criteria for cognitive impairment.
Results
The title and of 891 articles were screened, resulting in the identification of 90 potentially relevant articles while applying the eligibility criteria. After full‐text examination, 17 studies were included. Prevalence of cognitive impairment range from 25% before therapy, through 24% after therapy to 21% at maximal 1‐year follow‐up (FU). Compared to their pretreatment cognitive functioning, 24% of patients decline after treatment and 24% at 1‐year FU. Some studies also reported cognitive improvement showing that 15% and 31% of patients improve, respectively. In general, patients undergoing CT have a higher chance of cognitive impairment and decline than no‐CT patients and healthy controls.
Conclusions
This study shows that one out of four breast cancer patients shows cognitive impairment prior to treatment administration CT and a significant number of patients decline during the course of disease, suggesting that cognitive impairment is not exclusively related to CT and/or no‐CT therapies. This study shows that assessment of cognitive functioning, ideally over time, is crucial and may help the implementation of personalized rehabilitation pathways.
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To assess the efficacy and safety of Ginkgo for the treatment of people with diagnoses of cognitive impairment ...or dementia.
Chemotherapy‐induced cognitive impairment (“chemobrain”) is a frequent side‐effect in cancer survivors treated with paclitaxel (PTX). The mechanisms responsible for PTX‐induced cognitive impairment ...remain obscure, and there are no effective treatments or prevention strategies. Here, we test the hypothesis that PTX induces endothelial senescence, which impairs microvascular function and contributes to the genesis of cognitive decline. We treated transgenic p16‐3MR mice, which allows the detection and selective elimination of senescent cells, with PTX (5 mg/kg/day, 2 cycles; 5 days/cycle). PTX‐treated and control mice were tested for spatial memory performance, neurovascular coupling (NVC) responses (whisker‐stimulation‐induced increases in cerebral blood flow), microvascular density, blood–brain barrier (BBB) permeability and the presence of senescent endothelial cells (by flow cytometry and single‐cell transcriptomics) at 6 months post‐treatment. PTX induced senescence in endothelial cells, which associated with microvascular rarefaction, NVC dysfunction, BBB disruption, neuroinflammation, and impaired performance on cognitive tasks. To establish a causal relationship between PTX‐induced senescence and impaired microvascular functions, senescent cells were depleted from PTX‐treated animals (at 3 months post‐treatment) by genetic (ganciclovir) or pharmacological (treatment with the senolytic drug ABT263/Navitoclax) means. In PTX treated mice, both treatments effectively eliminated senescent endothelial cells, rescued endothelium‐mediated NVC responses and BBB integrity, increased capillarization and improved cognitive performance. Our findings suggest that senolytic treatments can be a promising strategy for preventing chemotherapy‐induced cognitive impairment.
Graphical representation depicting the proposed mechanism of chemotherapy‐induced cognitive impairment. PTX treatment induces endothelial senescence, which impairs microvascular function and contributes to cognitive decline. PTX‐treated mice exhibit microvascular rarefaction, neuroinflammation, and impaired cognitive performance. Senescent cells are eliminated from PTX‐treated animals using genetic or pharmacological means, which results in the restoration of endothelium‐mediated neurovascular coupling responses and blood‐brain barrier (BBB) integrity, increased capillarization, and improved cognitive performance.
Objectives
Cancer‐related cognitive impairment (CRCI) is associated with adverse work‐related outcomes in women living with a history of primary breast cancer. We explored the perceived impact of ...receiving adaptive cognitive training (dual n‐back training) or active control training (dual 1‐back training) on CRCI. Furthermore, we explored the perceived transfer effects of cognitive training on work‐related self‐management methods for cognitive impairment and work‐related outcomes such as career development.
Design
Longitudinal qualitative study.
Methods
A ‘framework’ analysis approach was used to analyse semi‐structured telephone interviews completed by women with a history of primary breast cancer before training (N = 40), one month (N = 30) and six months (N = 29) post‐training.
Results
Four main themes were identified: (1) impact of cognitive impairment at work, (2) perceived impact of cognitive training on impaired cognitive function, (3) perceived effects of training on work‐related self‐management methods for cognitive impairment and (4) perceived impact on women's career development and progression. Compared to baseline, women who received adaptive dual n‐back training reported sustained improvement in multiple cognitive domains including memory and attention up to six months post‐training when the follow‐up interviews were conducted. Perceived improvements in cognitive function were associated with greater self‐confidence and better emotional well‐being in work. These improvements were found to lower dependency on self‐management methods for cognitive impairment and enhance effectiveness as well as prompt career development or progression for many women. Although some findings of a similar nature were reported in the active control dual 1‐back training group the perceived effects were more pronounced and consistent in the dual n‐back group.
Conclusions
Adaptive cognitive training (dual n‐back training) improves perceived CRCI experienced by women in the workplace, enhancing their self‐confidence and general emotional well‐being. These perceived improvements, in turn, can decrease reliance on self‐management methods for cognitive impairment and improve work efficiency and contribute to career development and progression.
In this multicentre study in clinical settings, we assessed the accuracy of optimized procedures for FDG-PET brain metabolism and CSF classifications in predicting or excluding the conversion to ...Alzheimer's disease (AD) dementia and non-AD dementias.
We included 80 MCI subjects with neurological and neuropsychological assessments, FDG-PET scan and CSF measures at entry, all with clinical follow-up. FDG-PET data were analysed with a validated voxel-based SPM method. Resulting single-subject SPM maps were classified by five imaging experts according to the disease-specific patterns, as “typical-AD”, “atypical-AD” (i.e. posterior cortical atrophy, asymmetric logopenic AD variant, frontal-AD variant), “non-AD” (i.e. behavioural variant FTD, corticobasal degeneration, semantic variant FTD; dementia with Lewy bodies) or “negative” patterns. To perform the statistical analyses, the individual patterns were grouped either as “AD dementia vs. non-AD dementia (all diseases)” or as “FTD vs. non-FTD (all diseases)”. Aβ42, total and phosphorylated Tau CSF-levels were classified dichotomously, and using the Erlangen Score algorithm. Multivariate logistic models tested the prognostic accuracy of FDG-PET-SPM and CSF dichotomous classifications. Accuracy of Erlangen score and Erlangen Score aided by FDG-PET SPM classification was evaluated.
The multivariate logistic model identified FDG-PET “AD” SPM classification (Expβ = 19.35, 95% C.I. 4.8–77.8, p < 0.001) and CSF Aβ42 (Expβ = 6.5, 95% C.I. 1.64–25.43, p < 0.05) as the best predictors of conversion from MCI to AD dementia. The “FTD” SPM pattern significantly predicted conversion to FTD dementias at follow-up (Expβ = 14, 95% C.I. 3.1–63, p < 0.001). Overall, FDG-PET-SPM classification was the most accurate biomarker, able to correctly differentiate either the MCI subjects who converted to AD or FTD dementias, and those who remained stable or reverted to normal cognition (Expβ = 17.9, 95% C.I. 4.55–70.46, p < 0.001).
Our results support the relevant role of FDG-PET-SPM classification in predicting progression to different dementia conditions in prodromal MCI phase, and in the exclusion of progression, outperforming CSF biomarkers.
•Appropriate biomarkers measures improve early dementia diagnosis in MCI.•FDG-PET-SPM maps and CSF Aβ42 are the best predictors of AD dementia conversion.•FDG-PET-SPM maps accurately predict conversion to different dementia conditions.•A negative FDG-PET-SPM pattern characterizes stable or reverter MCI cases.
Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains.
Prospective cohort study.
We examined pre- versus post-KT cognition ...in patients waitlisted for KT at an academic center.
Transplant status. We measured cognitive function before KT (n=101), 3 months after KT (n=78), and 1 year after KT (n = 83).
Our primary outcome was change in cognitive function before versus after KT. We used standard neuropsychological tests to assess global cognition (Mini-Mental State Exam MMSE), episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test DSST, Trail Making Test TMT A), working memory/attention (Digit Span), executive function (TMT B), and semantic memory/verbal fluency/language (Category Fluency).
Using linear mixed model analysis, we evaluated the changes in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments.
Before KT, Logical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low compared with normative values from the National Alzheimer’s Coordinating Center data. Logical Memory I and II scores improved after KT (pre- vs post-KT, estimated group difference d=3.3, P<0.001 for Logical Memory I; d=4.27, P<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs normative values, d = −0.37, P=0.06 for Logical Memory I; d = −0.89, P=0.08 for Logical Memory II). Category Fluency (animal naming; d=2.4, P<0.001) and DSST (d=3.12, P=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs normative values, d = −5.17, P<0.001). MMSE, Digit Span, and TMT A and B scores did not change after KT.
Single-center study.
Episodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is therefore at least partly reversible with KT.
Cognitive impairment in kidney disease affects self-esteem, vocational abilities, quality of life, health care costs, and mortality. It is not clear whether kidney transplantation (KT) improves cognition and whether the improvement is uniform across cognitive domains. The distinction between reversible and irreversible cognitive impairment has important implications in the clinical care of patients before and after KT. We assessed cognition before KT and 3 months and 12 months after KT and discovered that episodic and verbal declarative memory normalized with KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function also improved with KT but did not reach normal levels. Cognitive impairment in kidney disease is therefore at least partly reversible.
Display omitted
Dementia treatment has become a global research priority, driven by the increase in the aging population. Punicalagin, the primary polyphenol found in pomegranate fruit, exhibits a variety of ...benefits. Today, a growing body of research is showing that punicalagin is a nutraceutical for the prevention of mild cognitive impairment (MCI). However, a comprehensive review is still lacking. The aim of this paper is to provide a comprehensive review of the physicochemical properties, origin and pharmacokinetics of punicalagin, while emphasizing the significance and mechanisms of its potential role in the prevention and treatment of MCI. Preclinical and clinical studies have demonstrated that Punicalagin possesses the potential to effectively target and enhance the treatment of MCI. Potential mechanisms by which punicalagin alleviates MCI include antioxidative damage, anti-neuroinflammation, promotion of neurogenesis, and modulation of neurotransmitter interactions. Overall, punicalagin is safer and shows potential as a therapeutic compound for the prevention and treatment of MCI, although more rigorous randomized controlled trials involving large populations are required.
Display omitted
A wide range of cognitive deficits, including memory loss associated with hippocampal dysfunction, have been widely reported in cancer survivors who received chemotherapy. Changes in both white ...matter and gray matter volume have been observed following chemotherapy treatment, with reduced volume in the medial temporal lobe thought to be due in part to reductions in hippocampal neurogenesis. Pre-clinical rodent models confirm that common chemotherapeutic agents used to treat various forms of non-CNS cancers reduce rates of hippocampal neurogenesis and impair performance on hippocampally-mediated learning and memory tasks. We review the pre-clinical rodent literature to identify how various chemotherapeutic drugs affect hippocampal neurogenesis and induce cognitive impairment. We also review factors such as physical exercise and environmental stimulation that may protect against chemotherapy-induced neurogenic suppression and hippocampal neurotoxicity. Finally, we review pharmacological interventions that target the hippocampus and are designed to prevent or reduce the cognitive and neurotoxic side effects of chemotherapy.
Cognitive decline is one of the most challenging issues for cancer survivors undergoing doxorubicin (DOX) based chemotherapy. Oxidative stress and inflammation primarily through tumor necrosis ...factor-alpha (TNF-α) are considered the key contributors to DOX-induced chemobrain. Berberine (BBR) has attracted much interest because of its anti-oxidative, anti-inflammatory and anti-apoptotic actions. This study aimed to evaluate the potential neuroprotective effect of BBR in DOX-induced neurodegeneration and cognitive deficits.
Chemobrain was induced by DOX i.p. injection at the dose of 2 mg/kg, once/week, for four consecutive weeks. Rats were treated with BBR (100 mg/kg, p.o.) for 5 days/week for four consecutive weeks.
BBR significantly attenuated behavioral defects in DOX-induced cognitive impairment. Besides, BBR reversed histopathological abnormalities. Mechanistically, it reversed DOX-induced neuroinflammation by attenuating NF-κB gene and protein expression in addition to diminishing expression of pro-inflammatory mediators (TNF-α and IL-1β), as well as apoptotic related factors (Bax, Bcl2 and Bax/Bcl2 ratio). Additionally, BBR activated the anti-oxidative defense via upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and manganese superoxide dismutase (MnSOD). BBR improved synaptic plasticity through cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). These effects were related through the modulation of Sirtuin1 (SIRT1) expression.
BBR is highlighted to induce neuroprotection against DOX-induced cognitive decline through modulating brain growth factors and imposing an anti-inflammatory, anti-apoptotic and anti-oxidative effects.
Display omitted
PDF
