Cognitive impairment following breast cancer treatments: an umbrella review.

OBJECTIVES: Cancer-related cognitive impairment (CRCI) refers to a cognitive decline associated with cancer or its treatments. While research into CRCI is expanding, evidence remains scattered due to differences in study designs, methodologies, and definitions. The present umbrella review aims to provide a comprehensive overview of the current evidence regarding the impact of different breast cancer therapies on cognitive functioning, with a particular focus on the interplay among objective cognitive deficits (ie, measured with standardized tests), subjective cognitive concerns, (ie, self-reported), and other mediating psycho-physical factors. METHODS: The search was made in Pubmed, Embase, and Scopus for articles published until July 2023, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis protocol. RESULTS: Chemotherapy and endocrine therapy appear consistently associated with CRCI in patients with breast cancer, primarily affecting memory, attention/concentration, executive functioning, and processing speed. Subjective cognitive concerns were often found weakly or not associated with neuropsychological test results, while overall CRCI seemed consistently associated with psychological distress, fatigue, sleep quality, and inflammatory and biological factors. CONCLUSION: Current evidence suggests that CRCI is common after chemotherapy and endocrine therapy for breast cancer. However, heterogeneity in study designs and the scarcity of studies on more recent treatments such as targeted therapies and immunotherapies, highlight the need for more systematic and harmonized studies, possibly taking into account the complex and multifactorial etiology of CRCI. This may provide valuable insights into CRCI's underlying mechanisms and potential new ways to treat it.

Facial emotion recognition in individuals with mild cognitive impairment: An exploratory study.

Understanding facial emotions is fundamental to interact in social environments and modify behavior accordingly. Neurodegenerative processes can progressively transform affective responses and affect social competence. This exploratory study examined the neurocognitive correlates of face recognition, in individuals with two mild cognitive impairment (MCI) etiologies (prodromal to dementia - MCI, or consequent to Parkinson's disease - PD-MCI). Performance on the identification and memorization of neutral and emotional facial expressions was assessed in 31 individuals with MCI, 26 with PD-MCI, and 30 healthy controls (HC). Individuals with MCI exhibited selective impairment in recognizing faces expressing fear, along with difficulties in remembering both neutral and emotional faces. Conversely, individuals with PD-MCI showed no differences compared with the HC in either emotion recognition or memory. In MCI, no significant association emerged between the memory for facial expressions and cognitive difficulties. In PD-MCI, regression analyses showed significant associations with higher-level cognitive functions in the emotional memory task, suggesting the presence of compensatory mechanisms. In a subset of participants, voxel-based morphometry revealed that the performance on emotional tasks correlated with regional changes in gray matter volume. The performance in the matching of negative expressions was predicted by volumetric changes in brain areas engaged in face and emotional processing, in particular increased volume in thalamic nuclei and atrophy in the right parietal cortex. Future studies should leverage on neuroimaging data to determine whether differences in emotional recognition are mediated by pathology-specific atrophic patterns.

Financial and numerical abilities: patterns of dissociation in neurological and psychiatric diseases.

The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice.

A Novel Paired Somatosensory-Cerebellar Stimulation Induces Plasticity on Cerebellar-Brain Connectivity.

The cerebellum receives and integrates a large amount of sensory information that is important for motor coordination and learning. The aim of the present work was to investigate whether peripheral nerve and cerebellum paired associative stimulation (cPAS) could induce plasticity in both the cerebellum and the cortex. In a cross-over design, we delivered right median nerve electrical stimulation 25 or 10 ms before applying transcranial magnetic stimulation over the cerebellum. We assessed changes in motor evoked potentials (MEP), somatosensory evoked potentials (SEP), short-afferent inhibition (SAI), and cerebellum-brain inhibition (CBI) immediately, and 30 min after cPAS. Our results showed a significant reduction in CBI 30 minutes after cPAS, with no discernible changes in MEP, SEP, and SAI. Notably, cPAS10 did not produce any modulatory effects on these parameters. In summary, cPAS25 demonstrated the capacity to induce plasticity effects in the cerebellar cortex, leading to a reduction in CBI. This novel intervention may be used to modulate plasticity mechanisms and motor learning in healthy individuals and patients with neurological conditions.

Effects of cognitive rehabilitation in Parkinson disease: a meta-analysis.

BACKGROUND AND OBJECTIVES: Cognitive symptoms are common in Parkinson's disease (PD) and affect patients' quality of life. Pharmacological interventions often do not improve such deficits that might benefit of cognitive rehabilitation. However, previous meta-analysis on this topic reported inconsistent results. Clarifying the efficacy of cognitive rehabilitation would be pivotal to optimize treatment and reduce care's costs. This meta-analysis aims at determining whether current literature lays in favor of the effectiveness of cognitive rehabilitation in PD and at understanding whether its effect might change depending on the trained cognitive domain. METHODS: We searched online databases for studies concerning cognitive rehabilitation in PD. Fourteen studies encompassing 767 participants were included. Analyses were conducted for each cognitive domain separately, examining several neuropsychological measures for each function. RESULTS: We found that rehabilitation improves global cognition, executive functions, and long- and short-term memory. CONCLUSION: The current body of research indicates that cognitive rehabilitation improves specific cognitive deficits in PD and that it should be tailored on patients' specific impairments. These interventions should be employed considering that not all the cognitive domains might benefit of a cognitive training. Finally, the high heterogeneity among studies suggests the need for more controlled clinical trials.

Predicting financial deficits from a standard neuropsychological assessment: preliminary evidence in mild cognitive impairment.

Patients with mild cognitive impairment (MCI) might experience difficulties in numerical and financial abilities of daily living that compromise their autonomy. The aim of the present work was to examine whether specific tests of the standard neuropsychological assessment could be used to predict these deficits in the clinical practice. Thirty-four MCI patients underwent a comprehensive clinical and neuropsychological examination including (1) a complete assessment of financial abilities and (2) a traditional neuropsychological assessment including measures of language, memory, executive functioning, reasoning, attention, and visuospatial abilities. The neuropsychological tests were used as predictors of the performance in everyday financial tasks using logistic regression analysis. Deficits in financial tasks including calculating percentages, using financial concepts and applying financial judgments were significantly predicted by tests of executive functions, language and short-term memory, while deficits in frequently encountered financial tasks activities such as item purchase and reading numbers could not be predicted by standard neuropsychological evaluations. Contingency tables on performance above/below clinical cut-offs evidenced some cases of financial deficits in the absence of cognitive deficits and, vice versa, some patients with cognitive decline did not show financial impairments. These results suggest that while some cognitive functions might be crucial for taking financial decisions, an ad hoc test of financial capacity is essential to make overall inferences about the everyday financial autonomy of MCI patients. This has potential implications for clinical and legal decisions that directly impact the individuals and their families.

Numerical activities of daily living: a short version.

Specific impairments in numerical functions may cause severe problems in everyday life that cannot be inferred from the available scales evaluating instrumental activities of daily living. The Numerical Activities of Daily living (NADL) is a battery designed to assess the patient's performance in everyday activities involving numbers (Informal Test) and in more scholastic capacities (Formal Test). A downside of this battery is its duration (45 min). The aim of the present study is to build a shorter version of NADL to make it more suitable for clinical and research purposes. The shortening procedure involved only the Formal test, and followed two steps: (i) a correlation of subtests with the general scores, and (ii) an item-analysis within the subtests previously showing higher correlations. Correlations between NADL-Short and NADL original version, and the new cut-offs were calculated. Lastly, the relationship between NADL-Short and other brief cognitive screening tests used in the clinical practice was evaluated in neurological patients and healthy controls. The NADL-Short includes the original Informal Test and the shortened Formal Test. It is a quick and easy clinical tool (15 min) to assess numerical abilities applied to informal and formal situations. It correlates highly with the original battery (Kendall's tau greater than 0.6 across tasks) and the cut-offs correctly identify impaired performance (accuracy of 95% or above). Correlation analysis showed a low positive correlation between NADL-Short and other brief cognitive scales. These findings suggest that it is appropriate to use specific tools to make inferences about a person's numerical abilities.

Neurocognitive correlates of numerical abilities in Parkinson's disease.

People with Parkinson's disease (PD) experience functional limitations early in the progression of the disease, showing, among other cognitive deficits, difficulties in mathematical abilities. The neural correlates of such abilities have been scarcely investigated in PD, and it is not known whether patients may exhibit difficulties only in formal numerical tasks (e.g., mental multiplications), or also in everyday activities involving numbers (i.e., informal numerical abilities such as time estimates). The present study investigated formal and informal numerical abilities in PD patients and explored their relationship with cortical and subcortical brain volume. We examined patients with PD and mild cognitive impairment (PD-MCI) and age-matched healthy controls (HCs) using the numerical activities of daily living (NADL) battery, assessing both scholastic numerical abilities (formal test), and the ability to use numbers in everyday life (informal test). We compared NADL performances in both groups. Within the PD group, we investigated the association between NADL and cortical and subcortical volumes using multiple linear regressions. The correlation with other cognitive tests was also explored. PD-MCI performed worse than HC in the formal NADL test. In PD-MCI patients, brain-behavior correlations showed two distinct patterns: cortical volumes correlated positively, while striatal volumes correlated negatively with NADL formal tasks. Both formal and informal tests correlated with measures of cognitive functioning. Our results suggest specific impairments in formal numerical abilities in PD-MCI, but not in everyday activities. While cortical atrophy is associated with worse performance, the negative correlations with subcortical regions suggest that their activation may reflect potential compensatory mechanisms.

Numerical Activities of Daily Living - Financial: a short version.

Financial capacity is the ability to manage money and finances according to a person's values and self-interests. In Italy, the first instrument specifically designed to assess financial capacity has recently been developed: the Numerical Activities of Daily Living - Financial (NADL-F). The aims of this study are (1) to prepare a shorter version of NADL-F and (2) to examine the relationship between the new short version and a measure of general cognitive functioning of comparable length, the MMSE. After an item analysis performed on NADL-F, the items presenting a higher internal consistency were selected. The resulting NADL-F Short is a reliable, easy to use, and quick to administer tool for assessing financial capacity both in clinical and legal practice. Correlation analysis showed a low positive correlation between four NADL-F Short tasks and the MMSE, for the healthy participants group. For the patient group, instead, a low-moderate correlation was found for all the NADL-F Short tasks, except one. Many participants scoring high in the MMSE (both healthy controls and neurological patients) showed low NADL-F Short scores. These findings suggest that it is not correct to use generic tools like the MMSE to make inferences on a person's financial capacity.

Numerical Activities of Daily Living - Financial (NADL-F): A tool for the assessment of financial capacities ‡.

Financial capacity is the ability to manage one's own finances according to self-interests. Failure in financial decisions and lack of independence when dealing with money can affect people's quality of life and are associated with neuropsychological deficits or clinical conditions such as mild cognitive impairment or Alzheimer's disease. Despite the importance of evaluating financial capacity in the assessment of patients with neuropsychological and psychiatric disorders, only a few tools have been developed. In the present article, the authors introduce the Numerical Activities of Daily Living - Financial (NADL-F) test, a new test to assess financial capacity in clinical populations. The NADL-F is relatively short, yet it encompasses the most common activities involving financial capacities. The NADL-F proved to have satisfactory psychometric properties and overall good validity for measuring financial abilities. Associations with performance on basic neuropsychological tests were investigated, in particular focusing on mathematical abilities as cognitive correlates of financial capacity. Results indicate that the NADL-F could be a useful tool to guide treatments for the enhancement of financial capacities. By sharing all materials and procedures, the authors hope to promote the development of further versions of the NADL-F in different languages, taking into account the necessary adjustments related to different socio-cultural contexts.

Working Memory Function in Children with Single Side Deafness Using a Bone-Anchored Hearing Implant: A Case-Control Study.

The importance of a good hearing function to preserve memory and cognitive abilities has been shown in the adult population, but studies on the pediatric population are currently lacking. This study aims at evaluating the effects of a bone-anchored hearing implant (BAHI) on speech perception, speech processing, and memory abilities in children with single side deafness (SSD). We enrolled n = 25 children with SSD and assessed them prior to BAHI implantation, and at 1-month and 3-month follow-ups after BAHI implantation using tests of perception in silence and perception in phonemic confusion, dictation in silence and noise, and working memory and short-term memory function in conditions of silence and noise. We also enrolled and evaluated n = 15 children with normal hearing. We found a statistically significant difference in performance between healthy children and children with SSD before BAHI implantation in the scores of all tests. After 3 months from BAHI implantation, the per-formance of children with SSD was comparable to that of healthy subjects as assessed by tests of speech perception, working memory, and short-term memory function in silence condition, while differences persisted in the scores of the dictation test (both in silence and noise conditions) and of the working memory function test in noise condition. Our data suggest that in children with SSD BAHI improves speech perception and memory. Speech rehabilitation may be necessary to further improve speech processing.

Functional changes in brain oscillations in dementia: a review.

A growing body of evidence indicates that several characteristics of electroencephalography (EEG) and magnetoencephalography (MEG) play a functional role in cognition and could be linked to the progression of cognitive decline in some neurological diseases such as dementia. The present paper reviews previous studies investigating changes in brain oscillations associated to the most common types of dementia, namely Alzheimer's disease (AD), frontotemporal degeneration (FTD), and vascular dementia (VaD), with the aim of identifying pathology-specific patterns of alterations and supporting differential diagnosis in clinical practice. The included studies analysed changes in frequency power, functional connectivity, and event-related potentials, as well as the relationship between electrophysiological changes and cognitive deficits. Current evidence suggests that an increase in slow wave activity (i.e., theta and delta) as well as a general reduction in the power of faster frequency bands (i.e., alpha and beta) characterizes AD, VaD, and FTD. Additionally, compared to healthy controls, AD exhibits alteration in latencies and amplitudes of the most common event related potentials. In the reviewed studies, these changes generally correlate with performances in many cognitive tests. In conclusion, particularly in AD, neurophysiological changes can be reliable early markers of dementia.

Use of Telemedicine to Improve Cognitive Functions and Psychological Well-Being in Patients with Breast Cancer: A Systematic Review of the Current Literature.

The diagnosis and side effects of breast cancer (BC) treatments greatly affect the everyday lives of women suffering from this disease, with relevant psychological and cognitive consequences. Several studies have reported the psychological effects of receiving a diagnosis of BC. Moreover, women undergoing anticancer therapies may exhibit cognitive impairment as a side effect of the treatments. The access to cognitive rehabilitation and psychological treatment for these patients is often limited by resources; women of childbearing age often encounter difficulties in completing rehabilitation programs requiring access to care institutions. Telemedicine, which provides health services using information and communication technologies, is a useful tool to overcome these limitations. In particular, telemedicine may represent an optimal way to guarantee cognitive rehabilitation, psychological support, and recovery to BC patients. Previous studies have reviewed the use of telemedicine to improve psychological well-being in BC patients, and a few have investigated the effect of telerehabilitation on cognitive deficits. This study systematically reviewed the evidence on the cognitive and psychological effects of telemedicine in BC patients. Current evidence suggests that telemedicine may represent a promising tool for the management of some psychological problems experienced by breast cancer patients, but more controlled studies are needed to clarify its effectiveness, especially for cognitive deficits. The results are also discussed in light of the intervening and modulating factors that may mediate both side effect occurrence and the success of the interventions.

White matter tract disconnection in Gerstmann's syndrome: Insights from a single case study.

It has been suggested that Gerstmann's syndrome is the result of subcortical disconnection rather than emerging from damage of a multifunctional brain region within the parietal lobe. However, patterns of white matter tract disconnection following parietal damage have been barely investigated. This single case study allows characterising Gerstmann's syndrome in terms of disconnected networks. We report the case of a left parietal patient affected by Gerstmann's tetrad: agraphia, acalculia, left/right orientation problems, and finger agnosia. Lesion mapping, atlas-based estimation of probability of disconnection, and DTI-based tractography revealed that the lesion was mainly located in the superior parietal lobule, and it caused disruption of both intraparietal tracts passing through the inferior parietal lobule (e.g., tracts connecting the angular, supramarginal, postcentral gyri, and the superior parietal lobule) and fronto-parietal long tracts (e.g., the superior longitudinal fasciculus). The lesion site appears to be located more superiorly as compared to the cerebral regions shown active by other studies during tasks impaired in the syndrome, and it reached the subcortical area potentially critical in the emergence of the syndrome, as hypothesised in previous studies. Importantly, the reconstruction of tracts connecting regions within the parietal lobe indicates that this critical subcortical area is mainly crossed by white matter tracts connecting the angular gyrus and the superior parietal lobule. Taken together, these findings suggest that this case study might be considered as empirical evidence of Gerstmann's tetrad caused by disconnection of intraparietal white matter tracts.

Prediction of rehabilitation induced motor recovery after stroke using a multi-dimensional and multi-modal approach.

Background: Stroke is a debilitating disease affecting millions of people worldwide. Despite the survival rate has significantly increased over the years, many stroke survivors are left with severe impairments impacting their quality of life. Rehabilitation programs have proved to be successful in improving the recovery process. However, a reliable model of sensorimotor recovery and a clear identification of predictive markers of rehabilitation-induced recovery are still needed. This article introduces the cross-modality protocols designed to investigate the rehabilitation treatment's effect in a group of stroke survivors. Methods/design: A total of 75 stroke patients, admitted at the IRCCS San Camillo rehabilitation Hospital in Venice (Italy), will be included in this study. Here, we describe the rehabilitation programs, clinical, neuropsychological, and physiological/imaging [including electroencephalography (EEG), transcranial magnetic stimulation (TMS), and magnetic resonance imaging (MRI) techniques] protocols set up for this study. Blood collection for the characterization of predictive biological biomarkers will also be taken. Measures derived from data acquired will be used as candidate predictors of motor recovery. Discussion/summary: The integration of cutting-edge physiological and imaging techniques, with clinical and cognitive assessment, dose of rehabilitation and biological variables will provide a unique opportunity to define a predictive model of recovery in stroke patients. Taken together, the data acquired in this project will help to define a model of rehabilitation induced sensorimotor recovery, with the final aim of developing personalized treatments promoting the greatest chance of recovery of the compromised functions.

Financial Decision-Making in Neurological Patients.

Financial abilities (FA) are a multi-dimensional domain comprising a wide range of conceptual, pragmatical, and judgmental skills ranging from basic abilities, such as bill payment, to high level abilities, such as financial decision-making (FDM). Preserved FDM abilities include the capacity to recognize fraud attempts, and they are fundamental for a person's independence. Previous studies have reported decreased FDM in older adults and in patients with mild cognitive impairment (MCI), who consequently become more susceptible to fraud attempts. However, FDM has scarcely been investigated in other neurological populations, and it is unclear whether FDM may be predicted by more basic FA. The aim of the present study was to investigate FDM across patients with MCI, Parkinson's disease (PD), or stroke, as well as healthy controls (HC), and to explore to what extent FDM could be inferred by other FA. We collected FDM and FA performances using the NADL-F short battery. Performances in the NADL-F short subtests were compared among groups. Additionally, the relationship between the scores at the FDM subtest and the performance obtained in other financial subtests of the NADL-F short were investigated for each group of participants. MCI patients performed worse than HC in FDM and in several FA domains. Conversely, FDM was relatively preserved in our sample of PD and stroke patients. In HC, FDM was associated with numeracy and financial knowledge applied to everyday situations, whereas this was true with some basic FA in both MCI and PD patients. No significant association was observed in stroke patients. Our results suggest that FDM is a complex ability, only partially inferable from other FA.

Dyscalculia in Early Adulthood: Implications for Numerical Activities of Daily Living.

Numerical abilities are fundamental in our society. As a consequence, poor numerical skills might have a great impact on daily living. This study analyzes the extent to which the numerical deficit observed in young adults with Developmental Dyscalculia (DD) impacts their activities of everyday life. For this purpose, 26 adults with DD and 26 healthy controls completed the NADL, a standardized battery that assesses numerical skills in both formal and informal contexts. The results showed that adults with DD had poorer arithmetical skills in both formal and informal settings. In particular, adults with DD presented difficulties in time and measure estimation as well as money usage in real-world numerical tasks. In contrast, everyday tasks regarding distance estimation were preserved. In addition, the assessment revealed that adults with DD were aware of their numerical difficulties, which were often related to emotional problems and negatively impacted their academic and occupational decisions. Our study highlights the need to design innovative interventions and age-appropriate training for adults with DD to support their numerical skills as well as their social and emotional well-being.

Collagen VI deficiency causes behavioral abnormalities and cortical dopaminergic dysfunction.

Mutations of genes coding for collagen VI (COL6) cause muscle diseases, including Ullrich congenital muscular dystrophy and Bethlem myopathy. Although COL6 genetic variants were recently linked to brain pathologies, the impact of COL6 deficiency in brain function is still largely unknown. Here, a thorough behavioral characterization of COL6-null (Col6a1-/-) mice unexpectedly revealed that COL6 deficiency leads to a significant impairment in sensorimotor gating and memory/attention functions. In keeping with these behavioral abnormalities, Col6a1-/- mice displayed alterations in dopaminergic signaling, primarily in the prefrontal cortex. In vitro co-culture of SH-SY5Y neural cells with primary meningeal fibroblasts from wild-type and Col6a1-/- mice confirmed a direct link between COL6 ablation and defective dopaminergic activity, through a mechanism involving the inability of meningeal cells to sustain dopaminergic differentiation. Finally, patients affected by COL6-related myopathies were evaluated with an ad hoc neuropsychological protocol, revealing distinctive defects in attentional control abilities. Altogether, these findings point towards a previously undescribed role for COL6 in the proper maintenance of dopamine circuitry function and its related neurobehavioral features in both mice and humans. This article has an associated First Person interview with the first author of the paper.

Efficacy of a Training on Executive Functions in Potentiating Rehabilitation Effects in Stroke Patients.

Cognitive impairment after a stroke has a direct impact on patients' disability. In particular, impairment of Executive Functions (EFs) interferes with re-adaptation to daily life. The aim of this study was to explore whether adding a computer-based training on EFs to an ordinary rehabilitation program, regardless of the specific brain damage and clinical impairment (motor, language, or cognitive), could improve rehabilitation outcomes in patients with stroke. An EF training was designed to have minimal motor and expressive language demands and to be applied to a wide range of clinical conditions. A total of 37 stroke patients were randomly assigned to two groups: a training group, which performed the EF training in addition to the ordinary rehabilitation program (treatment as usual), and a control group, which performed the ordinary rehabilitation exclusively. Both groups were assessed before and after the rehabilitation program on neuropsychological tests covering multiple cognitive domains, and on functional scales (Barthel index, Functional Independence Measure). The results showed that only patients who received the training improved their scores on the Attentional Matrices and Phonemic Fluency tests after the rehabilitation program. Moreover, they showed a greater functional improvement in the Barthel scale as well. These results suggest that combining an EF training with an ordinary rehabilitation program potentiates beneficial effects of the latter, especially in promoting independence in activities of daily living.