Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient's mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer's drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction

Bruxism and psychotropic medications

This is an accepted manuscript of an article published by Wiley in Progress in Neurology and Psychiatry on 13/02/2020, available online: https://wchh.onlinelibrary.wiley.com/doi/10.1002/pnp.560 The accepted version of the publication may differ from the final published version.Mental Health Disorders including schizophrenia, bipolar and schizoaffective disorders are often treated using psychotropic medications with evidence that some of these medications such as antipsychotics could be associated with significant oral side-effects. In this comprehensive review, we examine the psychotropic medications mechanisms of action and their oral side-effects, with specific focus on psychotropic medications and bruxism as a major oral health complication with a negative impact on the quality of life of mental health sufferers, relevant to psychiatrists, dentists and general practitioners. Bruxism could be caused by the antipsychotics extrapyramidal side-effects through dopaminergic receptors. Bruxism as a side-effect of psychotropic medications could result in significant consequences to oral health such as tooth structure destruction and irreversible harm to the temporomandibular joint. The review findings could assist in understanding the aetiology of bruxism, establish appropriate management plan, while supporting psychiatrists and dentists to detect temporomandibular dysfunctions (TMD) such as bruxism

Symptoms in different severity degrees of bruxism: a cross-sectional study

Objective: The aim of the present study was to evaluate symptoms of the muscle pain, sleep quality, oral health, anxiety, stress and depression in individuals with different severity degrees of bruxism. Methods: Seventy-two individuals with bruxism were enrolled in the study, classified into: moderate (n=25) and severe (n=47) bruxism. Pain intensity was assessed using the Visual Analogical Scale, pain threshold with algometer, sleep quality by the Pittsburgh Sleep Quality Index, oral health by the Oral Health Impact Profile, anxiety by the State-Trait Anxiety Inventory, stress by the Perceived Stress Scale and depression using the Beck Depression Inventory. The significance level considered was 5%. Results: The results showed that individuals with severe bruxism presented greater muscle pain intensity, sleep disorder, worse oral health, high anxiety level and dysphoria with statistically significant differences (pObjetivo: Avaliar sintomas de dor muscular, qualidade de sono, saúde bucal, ansiedade, estresse e depressão em indivíduos com diferentes graus de severidade do bruxismo. Métodos: Setenta e dois indivíduos com bruxismo participaram do estudo e foram classificados com bruxismo moderado (n=25) e severo (n=47). A intensidade da dor foi avaliada pela Escala Visual Analógica, limiar de dor com o algômetro, qualidade de sono pelo Índice de Qualidade de Sono de Pittsburgh, saúde bucal pelo Perfil de Impacto de Saúde Bucal, ansiedade pelo Inventário de Ansiedade Traço-Estado, estresse pela Escala de Estresse Percebido e depressão pelo Inventário de Depressão de Beck. O nível de significância considerado foi 5%. Resultados: Os resultados demonstraram que indivíduos com bruxismo severo apresentaram maior intensidade de dor muscular, distúrbio do sono, pior qualidade de saúde bucal, elevado grau de ansiedade e disforia, com diferenças estatisticamente significantes (p;0,05). Conclusão: Os dados sugerem que indivíduos com bruxismo severo tem sintomas mais intensos. Eles apresentam maior intensidade de dor muscular, alterações na qualidade do sono e saúde bucal, ansiedade e depressão do que indivíduos com bruxismo moderado. Porém, ambos apresentam similaridade no estresse.Objetivo: Evaluar los síntomas dolor muscular, calidad de sueño, salud bucal, ansiedad, estrés y depresión en sujetos con diferentes niveles de gravedad del bruxismo. Método: Participaron del estudio 72 personas con bruxismo, clasificado según los niveles moderado (n=25) y grave (n=47). Se evaluaron la intensidad del dolor mediante la Escala Visual Analógica, umbral de dolor con algómetro, la calidad de sueño por el Índice de Calidad de Sueño de Pittsburgh, la salud bucal mediante el Perfil del Impacto de Salud Bucal, la ansiedad por el Inventario de Ansiedad Rasgo-Estado, el estrés mediante la Escala de Estrés Percibido y la depresión por el Inventario de Depresión de Beck. Se consideró el nivel de significación de 5%. Resultados: Los sujetos con bruxismo grave presentaron más intensamente dolor muscular, trastorno de sueño, peor calidad de salud bucal, alto grado de ansiedad y disforia, con diferencias estadísticamente significativas (p;0,05). Conclusión: Los datos mostraron que los sujetos con bruxismo grave sufren síntomas más intensos. A pesar de sufrir síntomas más intensos de dolor muscular, calidad de sueño y salud bucal alterada, ansiedad y depresión que los sujetos con bruxismo moderado, el estrés está presente en los dos niveles de bruxismo

Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research

10.1371/journal.pone.0081234PLoS ONE812-POLN

Leptin Replacement Improves Cognitive Development

Leptin changes brain structure, neuron excitability and synaptic plasticity. It also regulates the development and function of feeding circuits. However, the effects of leptin on neurocognitive development are unknown.To evaluate the effect of leptin on neurocognitive development.A 5-year-old boy with a nonconservative missense leptin gene mutation (Cys-to-Thr in codon 105) was treated with recombinant methionyl human leptin (r-metHuLeptin) at physiologic replacement doses of 0.03 mg/kg/day. Cognitive development was assessed using the Differential Ability Scales (DAS), a measure of general verbal and nonverbal functioning; and selected subtests from the NEPSY, a measure of neuropsychological functioning in children.Prior to treatment, the patient was morbidly obese, hypertensive, dyslipidemic, and hyperinsulinemic. Baseline neurocognitive tests revealed slower than expected rates of development (developmental age lower than chronological age) in a majority of the areas assessed. After two years, substantial increases in the rates of development in most neurocognitive domains were apparent, with some skills at or exceeding expectations based on chronological age. We also observed marked weight loss and resolution of hypertension, dyslipidemia and hyperinsulinemia.We concluded that replacement with r-metHuLeptin is associated with weight loss and changes in rates of development in many neurocognitive domains, which lends support to the hypothesis that, in addition to its role in metabolism, leptin may have a cognitive enhancing role in the developing central nervous system.ClinicalTrials.gov NCT00659828

Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis