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Background/Aim: Metformin has been associated with vitamin B 12 (cobalamin) deficiency, pushing scientific societies such as the American Diabetes Association and the European Association for the Study of Diabetes to emphasise the need for screening B 12 levels, without specific metformin doses or exposure durations triggering this screening. Robust data regarding the prevalence of B 12 deficiency in metformin-treated patients in Portugal are currently lacking. Aim of this study was to identify the prevalence of B 12 deficiency in a sample of diabetic patients taking metformin. Secondary objectives were determining the minimum dose and minimum and median time exposure time leading to this deficiency and identifying the average duration of metformin use in the patients with this deficiency. Methods: Descriptive and cross-sectional observational study was performed on a sample of 79 users from a population of 714 diabetic patients on metformin. Inclusion criteria comprised individuals aged 18 or older, receiving metformin for at least 1 month and voluntarily participating in the study. Exclusion criteria included a history of gastrectomy or B 12 supplementation. Results: A prevalence of 25.3 % of vitamin B 12 deficiency was identified in the study sample. Minimum doses of 500 mg of metformin per day and a minimum exposure period of 1 year were associated with B 12 deficiency. An average exposure time of 5.33 years was identified. Conclusion: These results align with the prevalence described in the few international studies and should alert physicians to potential clinical manifestations of this deficiency, such as anaemia and neurological symptoms like neuropathy.

Introduction: Lithium is one of the main drugs used in Bipolar Affective Disorder. However, it has a narrow therapeutic window, which requires close monitoring and progressive dose adjustment, according to serum levels, clinical response and the appearance of side effects. The term 'SILENT' explains descriptively persistent neurological sequelae related to lithium salt intoxication when symptoms persist for more than 2 months after stopping treatment. SILENT Syndrome is more common in females, at ages ranging from 21 to 77 years and is characterized mainly by avermian-type cerebellar disorder, persistent extrapyramidal syndrome, brainstem dysfunction and dementia of varying severity. It can also result in apraxia of the body, changes in the coordination and balance, dysarthria, as well as intentional and kinetic cerebellar tremor, involuntary movements of orofacial dyskinesias or resting tremor. Objectives: The authors intend to review the relevant and current literature in order to extend the knowledge about this condition and find the best conducts for clinical practice. Methods: Non-systematic literature review. Results: Complications from the use of lithium known in the medical literature include mainly nephrotoxicity, endocrine alterations and neurotoxicity. The neurotoxic effects of lithium usually occur at high serum concentrations. However, they can also occur with lithium in the therapeutic range, and memory, attention and ataxia impairment may be some of the permanent sequelae. The etiopathogenesis is unclear, but demyelination has been detected in multiple brain regions, mainly in the cerebellum. The mechanism of lithium-induced cerebellar injury is believed to be mediated by the entry of calcium into the cells of this organ. The main factors that predispose to greater side effects and risk of toxicity are patients with decreased renal function, advanced age, use of diuretics, dementia, pregnancy, low sodium intake and physical illness with vomiting and/or diarrhea. Conclusions: Lithium is a drug used mostly in affective disorders and given the narrow therapeutic window, it requires close monitoring in order to avoid side effects that can be permanent. In this way, it is important to review the factors that increase the lithium toxicity and make recommendations about it. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: The United States of America are currently facing a public health crisis characterized by the abuse of synthetic opioids, notably Fentanyl, and the veterinary sedative Xylazine. While each of these substances has been associated with significant risks, their current misuse presents a formidable challenge to healthcare professionals, law enforcement agencies and policymakers. While the opioid epidemic has long held the nation in its grip, the emergence of Xylazine as complementary agent in substance abuse has added a disturbing layer of complexity to an already terrible situation, due to its cost-cutting, an increase in its addictive properties and its ability to extend the duration of the opioid with which it is combined. Objectives: The authors intend to review the relevant and current literature in order to extend the knowledge about this condition and find the best conducts for clinical practice. Methods: Non-systematic literature review Results: Various regions of the United States are facing a troubling surge in the co-abuse of Fentanyl, a potent synthetic opioid many times more potent than morphine, and Xylazine, a veterinary sedative and muscle relaxant, particularly in urban areas. The motivations for this combination appear to vary, ranging from the enhanced euphoria to cost-saving measures, further fueling its prevalence. However, the consequences are devastating. Both substances depress the central nervous system, with a sharp increase in overdose deaths and emergency medical services are strained to their limits in responding to these crises. Law enforcement agencies are facing a daunting task in curtailing the distribution of these substances, often grappling with clandestine networks that exploit the accessibility of these drugs. Conclusions: The concurrent abuse of Fentanyl and Xylazine represents a critical public health challenge in the United States of America, demanding immediate attention and a multidisciplinary response. Failure to address this issue comprehensively will have profound implications for the well-being of individuals, families and communities across the nation. It is imperative to mobilize resources, foster interdisciplinary collaboration and develop evidence-based policies to combat this dual-threat crisis. Novel intervention strategies, including community education programs, targeted outreach efforts, and supervised consumption facilities, are urgently needed to address this complex issue. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Abstract Background Spotted cDNA microarrays generally employ co-hybridization of fluorescently-labeled RNA targets to produce gene expression ratios for subsequent analysis. Direct comparison of two RNA samples in the same microarray provides the highest level of accuracy; however, due to the number of combinatorial pair-wise comparisons, the direct method is impractical for studies including large number of individual samples (e.g., tumor classification studies). For such studies, indirect comparisons using a common reference standard have been the preferred method. Here we evaluated the precision and accuracy of reconstructed ratios from three indirect methods relative to ratios obtained from direct hybridizations, herein considered as the gold-standard. Results We performed hybridizations using a fixed amount of Cy3-labeled reference oligonucleotide (RefOligo) against distinct Cy5-labeled targets from prostate, breast and kidney tumor samples. Reconstructed ratios between all tissue pairs were derived from ratios between each tissue sample and RefOligo. Reconstructed ratios were compared to (i) ratios obtained in parallel from direct pair-wise hybridizations of tissue samples, and to (ii) reconstructed ratios derived from hybridization of each tissue against a reference RNA pool (RefPool). To evaluate the effect of the external references, reconstructed ratios were also calculated directly from intensity values of single-channel (One-Color) measurements derived from tissue sample data collected in the RefOligo experiments. We show that the average coefficient of variation of ratios between intra- and inter-slide replicates derived from RefOligo, RefPool and One-Color were similar and 2 to 4-fold higher than ratios obtained in direct hybridizations. Correlation coefficients calculated for all three tissue comparisons were also similar. In addition, the performance of all indirect methods in terms of their robustness to identify genes deemed as differentially expressed based on direct hybridizations, as well as false-positive and false-negative rates, were found to be comparable. Conclusion RefOligo produces ratios as precise and accurate as ratios reconstructed from a RNA pool, thus representing a reliable alternative in reference-based hybridization experiments. In addition, One-Color measurements alone can reconstruct expression ratios without loss in precision or accuracy. We conclude that both methods are adequate options in large-scale projects where the amount of a common reference RNA pool is usually restrictive.

A new model of reserve, the Sensory, Emotional, and Cognitive Reserve (SEC) model, has been recently proposed, but so far this model has not been operationalized in instruments to evaluate the different domains of the reserve. This study introduces the SEC reserve inventory (SECri) along with preliminary data obtained from a study involving 57 adults, aged 35 and older. The SECri assesses the SEC domains using specific proxies: (a) sensory reserve (SR) through sensory acuity and sensory perception proxies; (b) emotional reserve (ER) through life events, resilience, and emotional regulation proxies; and (c) cognitive reserve (CR) through education, occupation, socioeconomic status, bilingualism, leisure activities, and personality traits proxies. Key features of SECri include self- and informant-report forms, fine-grained response scales, and the evaluation of reserve development across the lifespan. Findings on the acceptability, convergent validity between SECri domains and validated tests for the same constructs, internal consistency of each domain, and predictive validity of Montreal Cognitive Assessment scores support further research with this inventory. Future studies should consider determining SECri's psychometric properties in clinical and subclinical conditions to evaluate its prognostic value in cases of neurocognitive decline.

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and postharvest regulation), plant responses to environmental signals (endoplasmic-reticulum-associated degradation, chloroplast-associated degradation, drought tolerance, and the growth-defense trade-off), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

The evaluation of Activities of Daily Living (ADL) has become a critical issue in neuropsychology, but existing instruments for evaluating ADL have some limitations. This work aims to propose a new instrument to evaluate ADL, the ADL Inventory (ADLI), for which we present preliminary data., The ADLI was developed based on a comprehensive model of the stages of test development and following a combined framework of the World Health Organization's International Classification of Functioning, Disability, and Health and the American Occupational Therapy Association models., Besides sociodemographic information, ADLI includes 144 items, organized into four sections: (a) basic ADL; (b) IADL; (c) advanced ADL; and (d) factors influencing functionality. The main characteristics of ADLI are: having self- and informant-report forms; including items focused on different sensory and neurocognitive functions; individualizing the progression along items considering the person's functionality; considering the impact of several factors on functionality; and using a large response scale. Preliminary data of predictive and convergent validity for ADLI are presented. The preliminary study comprised 15 older adults. The Addenbrooke's Cognitive Examination - III, the Barthel Index, and the Instrumental Activities of Daily Living (IADL) Scale were applied to determine the predictive and convergent validity of ADLI.

Immunosuppressive macrophages restrict anti-cancer immunity in glioblastoma (GBM). Here, we studied the contribution of microglia (MGs) and monocyte-derived macrophages (MDMs) to immunosuppression and mechanisms underlying their regulatory function. MDMs outnumbered MGs at late tumor stages and suppressed T cell activity. Molecular and functional analysis identified a population of glycolytic MDM expressing GLUT1 with potent immunosuppressive activity. GBM-derived factors promoted high glycolysis, lactate, and interleukin-10 (IL-10) production in MDMs. Inhibition of glycolysis or lactate production in MDMs impaired IL-10 expression and T cell suppression. Mechanistically, intracellular lactate-driven histone lactylation promoted IL-10 expression, which was required to suppress T cell activity. GLUT1 expression on MDMs was induced downstream of tumor-derived factors that activated the PERK-ATF4 axis. PERK deletion in MDM abrogated histone lactylation, led to the accumulation of intratumoral T cells and tumor growth delay, and, in combination with immunotherapy, blocked GBM progression. Thus, PERK-driven glucose metabolism promotes MDM immunosuppressive activity via histone lactylation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The concept of ecological validity (EV) in neuropsychological interventions (NI) has been consistently advocated, but there is a lack of reviews focused on how EV is operationalized in NI programmes. This review aims to address this gap by exploring the outcome measures more commonly used for assessing EV and to understand the main characteristics of programmes with good EV., Method: A literature search was conducted to identify studies that examined the EV of NI programmes, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Collaboration Guidelines., Results: A total of twenty-seven studies were included in this review. Among these, only three studies explicitly described the procedures used to assess EV. Additionally, almost half of the studies assumed that interventions had good EV based on the characteristics of the programmes. The inconsistent assessment of EV of NI programmes prevented the identification of specific characteristics of programmes demonstrating good EV., Conclusion: This systematic review reveals a significant gap in the literature concerning the operationalization of EV within the field of NI. Further research is required to establish a consistent definition of EV in the context of NI and to develop criteria for its effective operationalization.

Objective: Recently, there has been a growing interest in operationalizing and measuring cognitive reserve (CR) for clinical and research purposes. This umbrella review aims to summarize the existing systematic and meta-analytic reviews about measures of CR. Method: A literature search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the guidelines of Aromataris et al. (2015) to identify the systematic reviews and meta-analysis involving the assessment of CR. The methodological quality of the papers included in this umbrella review was assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) and Specialist Unit for Review Evidence (SURE). Results: Thirty-one reviews were identified, sixteen of which were systematic reviews, and fifteen were meta-analyses. Most of the reviews had a critically low quality , according to AMSTAR-2. The reviews included between two and 135 studies. Most of the papers focused on older adults, mainly those with dementia. CR was measured using one to six proxies, but most considered each proxy separately. The most assessed proxies of CR were education on its own, combined with occupation and/or engagement in activities or combined with parental education, bilingualism, and engagement in activities when four CR proxies were studied. Most of the studies included in higher quality reviews focused on three proxies, with education and engagement in activities being the most evaluated using CR questionnaires. Conclusion: Despite the growing interest in measuring CR, its operationalization did not improve since the last umbrella review in this field.

The literature on neuropsychological intervention (NI) uses a variety of terms to refer to equivalent constructs, making it difficult to compare intervention programmes and their outcomes. The purpose of this work is to propose a unified terminological framework for describing NI programmes. The terminological framework was developed based on a previous proposal for common terminology by Johnstone and Stonnington (Rehabilitation of neuropsychological disorders: A practical guide for rehabilitation professionals. Psychology Press, 2011) and driven by Cognitive Psychology concepts. The terminological framework was organized into two sections: (a) NI, which includes types of NI, methods and approaches, instructional methods, and strategies; and (b) neurocognitive functions, which include temporal and spatial orientation, sensation, perception, visuo-constructional abilities, attention, memory, language, reasoning of several sorts (e.g., abstract reasoning, and numerical reasoning), and executive functions. Most NI tasks target a main neurocognitive function, but there are underlying neurocognitive functions that may impair performance in the former. Since it is difficult to create a task that is solely focused on one neurocognitive function, the proposed terminology should not be viewed as a taxonomy, but rather as dimensional, with the same task allowing to work different functions, in varying grades. Adopting this terminological framework will allow to define the targeted neurocognitive functions more accurately and simplify the comparison between NI programmes and their outcomes. Future research should focus on describing the main techniques/strategies for each neurocognitive function and non-cognitive interventions., (© 2023 The British Psychological Society.)

Background: Congenital heart disease (CHD) is a leading cause of childhood morbidity, with an estimated prevalence of 0.8-1%. However, advances in diagnosis and treatment now allow 90% of childhood CHD patients to survive to adulthood, leading to increased interest in their quality of life (QoL). In this study, we examine the impact of clinical and psychosocial variables, including the number of surgical interventions (NSI), age at surgery, school achievement, and social support, as mediating factors of QoL in CHD patients., Methods: The study included 233 CHD patients (132 males) with an average age of 15.2 ± 2.07 years, including 80 with cyanotic CHD and 153 with acyanotic CHD. The severity of illness ranged from mild to severe, with 30 patients having a severe illness, 119 having a moderate illness, and 84 having a mild illness. One-hundred-sixty-three patients underwent surgery. Clinical data on diagnosis, the severity of CHD, the type of CHD, and surgical interventions were collected from patient records, and a semi-structured interview was conducted to explore the relationship between CHD diagnosis and various aspects of life. QoL was assessed using the Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-Bref) questionnaire., Results: Ten mediation models were analyzed, each with three hypotheses (paths). In all models the first hypothesis was supported. Analyses of the second and third hypotheses revealed three feasible models of mediation through the effect of NSI on QoL in CHD patients., Conclusions: Our findings indicate that patients with more severe and cyanotic CHD generally require more surgical interventions, which may increase the risk of negative outcomes and affect patients' perception of QoL. These results have important implications for healthcare providers and psychologists who work with childhood CHD patients., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Plants need to integrate internal and environmental signals to mount adequate stress responses. The NUCLEAR PORE COMPLEX (NPC) component HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1) is emerging as such an integrator, affecting responses to cold, heat, light, and salinity. Stress conditions often converge in a low-energy signal that activates SUCROSE NON-FERMENTING 1-RELATED KINASE 1 (SnRK1) to promote stress tolerance and survival. Here, we explored the role of HOS1 in the SnRK1-dependent response to low-energy stress in Arabidopsis thaliana, using darkness as a treatment and a combination of genetic, biochemical, and phenotypic assays. We show that the induction of starvation genes and plant tolerance to prolonged darkness are defective in the hos1 mutant. HOS1 interacts physically with the SnRK1α1 catalytic subunit in yeast two-hybrid assays and in planta, and the nuclear accumulation of SnRK1α1 is reduced in the hos1 mutant. Likewise, another NPC mutant, nup160, exhibits lower activation of starvation genes and decreased tolerance to prolonged darkness. Importantly, defects in low-energy responses in the hos1 background are rescued by fusing SnRK1α1 to a potent nuclear localization signal or by sugar supplementation during the dark treatment. Altogether, this work demonstrates the importance of HOS1 for the nuclear accumulation of SnRK1α1, which is key for plant tolerance to low-energy conditions., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Objectives: The main objectives of this study are to identify the dimensions of Ecological Validity (EV) within the definitions of this concept, understand how they are operationalized in neurocognitive tests, and propose a checklist for EV attributes in neurocognitive tests., Method: A systematized review was combined with content analysis of the selected papers, using the inductive method. We analyzed 82 studies on the EV of neurocognitive tests, 19 literature reviews and 63 empirical studies. Based on this review, we identified the relevant criteria for evaluating EV., Results: EV is a multidimensional concept with two main dimensions: representativeness and generalization. Representativeness involves the subdimensions simplicity-complexity and artificial-natural and several criteria organized on a continuum from low EV to high EV. Generalization is dependent on representativeness and is influenced by different cognitive and non-cognitive factors. We propose six stages for operationalizing EV, from defining the objectives of the neurocognitive assessment to the methodology for scoring and interpreting the results., Conclusion: This systematized review helps to operationalize the concept of EV by providing a tool for evaluating and improving EV while developing new tests. Further studies with a longitudinal design can compare the predictive value of tests with higher versus lower EV-checklist scores.Key pointsQuestion: Understand the definition of EV, its dimensions and subdimensions, how EV is operationalized in neurocognitive tests and propose a checklist for the EV attributes of neurocognitive tests.Findings: The primary findings were that representativeness and generalization are the main dimensions of EV. Representativeness involves several subdimensions, whereas generalization is dependent on representativeness and is influenced by cognitive and non-cognitive factors. We provided an EV-checklist organized into six parts.Importance: The EV-checklist can be used to guide the development of ecologically valid neurocognitive tests and/or assess the EV of existing ones.Next steps: Examine the predictive value of tests that have higher EV-checklist scores.

SUCROSE NON-FERMENTING1 (SNF1)-RELATED KINASE 1 (SnRK1) is an evolutionarily conserved protein kinase with key roles in plant stress responses. SnRK1 is activated when energy levels decline during stress, reconfiguring metabolism and gene expression to favour catabolism over anabolism, and ultimately to restore energy balance and homeostasis. The capacity to efficiently redistribute resources is crucial to cope with adverse environmental conditions and, accordingly, genetic manipulations that increase SnRK1 activity are generally associated with enhanced tolerance to stress. In addition to its well-established function in stress responses, an increasing number of studies implicate SnRK1 in the homeostatic control of metabolism during the regular day-night cycle and in different organs and developmental stages. Here, we review how the genetic manipulation of SnRK1 alters central metabolism in several plant species and tissue types. We complement this with studies that provide mechanistic insight into how SnRK1 modulates metabolism, identifying changes in transcripts of metabolic components, altered enzyme activities, or direct regulation of enzymes or transcription factors by SnRK1 via phosphorylation. We identify patterns of response that centre on the maintenance of sucrose levels, in an analogous manner to the role described for its mammalian orthologue in the control of blood glucose homeostasis. Finally, we highlight several knowledge gaps and technical limitations that will have to be addressed in future research aiming to fully understand how SnRK1 modulates metabolism at the cellular and whole-plant levels., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

The goal of this work was to examine whether elevated iodine intake was associated with adverse effects on IQ among school-age children in Portugal. In a representative sample of children from the north of the country, IQ percentiles by age (assessed with Raven’s Colored Progressive Matrices) were dichotomized to <50 (“below-average” IQs) and ≥50. Morning urine iodine concentrations, corrected for creatinine, were dichotomized to <250 µg/g and ≥250 µg/g, according to the European Commission/Scientific Committee on Food’s tolerable upper level of daily iodine intake for young children. Data were examined with Chi-square tests, logistic regression, and GLM univariate analysis. The sample (N = 1965) was classified as generally iodine-adequate (median urinary iodine concentration = 129 µg/L; median iodine-to-creatinine ratio = 126 µg/g) according to the WHO’s criteria. A greater proportion of children in the ≥250 µg/g group had below-average IQs, compared to children with less than 250 µg/g (p = 0.037), despite a sizable (though non-significant) proportion of children in the less-than-250 µg/g group also presenting below-average IQs, at the bottom of the iodine distribution (<50 µg/g). The proportion of below-average IQs increased with increasingly elevated iodine concentrations (p = 0.047). The association remained significant after the adjustment for confounders, with the elevated iodine group showing increased odds of having below-average IQs when compared with the non-elevated iodine group (OR 1.55; 95% CI 1.11−2.17; p = 0.011). Consistently, the former group presented a lower mean IQ than the latter (p = 0.006). High iodine intake was associated with lower IQs even in a population classified as iodine-adequate. These results bear on child cognition and on initiatives involving iodine supplementation.

Many plants, including Arabidopsis (Arabidopsis thaliana), accumulate starch in the daytime and remobilize it to support maintenance and growth at night. Starch accumulation is increased when carbon is in short supply, for example, in short photoperiods. Mobilization is paced to exhaust starch around dawn, as anticipated by the circadian clock. This diel pattern of turnover is largely robust against loss of day, dawn, dusk, or evening clock components. Here, we investigated diel starch turnover in the triple circadian clock mutant lhy cca1 elf3, which lacks the LATE ELONGATED HYPOCOTYL and the CIRCADIAN CLOCK-ASSOCIATED1 (CCA1) dawn components and the EARLY FLOWERING3 (ELF3) evening components of the circadian clock. The diel oscillations of transcripts for the remaining clock components and related genes like REVEILLE and PHYTOCHROME-INTERACING FACTOR family members exhibited attenuated amplitudes and altered peak time, weakened dawn dominance, and decreased robustness against changes in the external light-dark cycle. The triple mutant was unable to increase starch accumulation in short photoperiods. However, it was still able to pace starch mobilization to around dawn in different photoperiods and growth irradiances and to around 24 h after the previous dawn in T17 and T28 cycles. The triple mutant was able to slow down starch mobilization after a sudden low-light day or a sudden early dusk, although in the latter case it did not fully compensate for the lengthened night. Overall, there was a slight trend to less linear mobilization of starch. Thus, starch mobilization can be paced rather robustly to dawn despite a major disruption of the transcriptional clock. It is proposed that temporal information can be delivered from clock components or a semi-autonomous oscillator., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Introduction: The main purpose of this manuscript is to critically review the Multisensory Integration (MI) training programs applied to older adults, their characteristics, target sensory systems, efficacy, assessment methods, and results. We also intend to propose an integrated framework to support combined interventions of neurocognitive and sensory training., Areas Covered: A critical review was conducted covering the most relevant literature on the MI training programs applied to older adults. Two MI training programs applied to cognitively healthy older adults were found: (a) audio-visual temporal discrimination training and (b) simultaneity judgment training. Both led to the improvement of the MI between pre- and post-training. However, only the audio-visual temporal discrimination training led to the generalization of the improvements to another MI task., Expert Opinion: Considering the relationship between sensory and cognitive functioning, this review supports the potential advantages of combining MI with neurocognitive training in the rehabilitation of older adults. We suggested that this can be achieved within the framework of Branched Programmed Neurocognitive Training (BPNT). Criteria for deciding the most suitable multisensory intervention, that is, MI or Multisensory Stimulation, and general guidelines for the development of MI intervention protocols with older adults with or without cognitive impairment are provided.

Purpose: The efficacy studies of neurocognitive training have focused on the components of the programmes and general methodological questions, not presenting a rationale for the individualization of the intervention, even though this is an essential factor for efficacy. The main objective of this manuscript is to propose a framework for the individual planning of neurocognitive training sessions based on the results of neuropsychological assessment., Methods: The proposed framework is coined Branched Programmed Neurocognitive Training (BPNT). BPNT is based on the programmed learning approach and inspired on the Luria's neurocognitive model. The main premises of this framework are the interdependence and hierarchical organization of the cognitive functions, and the individualization of neurocognitive training with multiple patient-tailored paths., Results: The BPNT framework provides guidelines for planning an individualized neurocognitive training in four stages., Conclusions: The potential advantages of this proposal are discussed at various levels, including the role of reward in neurocognitive training and the potential effects of the model on the maintenance and generalization of intervention results. The BPNT framework can be used as an algorithm for the development and adaptation of paper and pencil programmes, as well as computerized rehabilitation platforms. Studies are in place to examine the feasibility of this framework.Implications for rehabilitationIndividualized neurocognitive training guided by neuropsychological assessment is most likely to be effective.Branched Programmed Neurocognitive Training (BPNT) model provides guidelines to organize the neurocognitive training based on the results of neuropsychological assessment.BPNT is based on the programmed learning model and the Luria neurocognitive model, addresses the role of reward in neurocognitive training and considers the fundamental principle of Errorless Learning.BPNT can be used as an algorithm for the development and adaptation of paper and pencil programmes and computerized rehabilitation platforms.