A case-control study of psychosocial factors and their relationship to impairment and functionality in multiple sclerosis.

The stress effect on multiple sclerosis remains unclear. Moderating psychosocial factors may be involved. This study compares some of them in people with multiple sclerosis and healthy controls, and their association with disease parameters. Coping style, social support, anxiety, alexithymia and early-life stress were measured, along with impairment and functionality. People with multiple sclerosis scored significantly higher on anxiety, alexithymia, and avoidance and instinctive coping but lower in social support. No differences were found in early-life stress. Impairment was related to avoidance, and functionality to avoidance and anxiety. Psychotherapeutic approaches focused on these psychosocial factors may improve functionality, impairment and quality of life in people with multiple sclerosis.

Stress and multiple sclerosis: A systematic review considering potential moderating and mediating factors and methods of assessing stress.

Research about the effects of stress on multiple sclerosis has yielded contradictory results. This study aims to systematically review the evidence focusing on two possible causes: the role of stress assessment and potential moderating and mediating factors. The Web of Knowledge (MEDLINE and Web of Science), Scopus, and PsycINFO databases were searched for relevant articles published from 1900 through December 2014 using the terms "stress*" AND "multiple sclerosis." Twenty-three articles were included. Studies focused on the effect of stress on multiple sclerosis onset (n = 9) were mostly retrospective, and semi-structured interviews and scales yielded the most consistent associations. Studies focused on multiple sclerosis progression (n = 14) were mostly prospective, and self-reported diaries yielded the most consistent results. The most important modifying factors were stressor duration, severity, and frequency; cardiovascular reactivity and heart rate; and social support and escitalopram intake. Future studies should consider the use of prospective design with self-reported evaluations and the study of moderators and mediators related to amount of stress and autonomic nervous system reactivity to determine the effects of stress on multiple sclerosis.

Reelin signaling pathway genotypes and Alzheimer disease in a Spanish population.

BACKGROUND: Several reports suggest that the reelin protein could play a role in Alzheimer pathophysiology. This led us to ask whether genetic variability in the reelin pathway may increase the risk of developing Alzheimer disease (AD) or mild cognitive impairment (MCI). METHODS: This was a case-control study in which neuropsychological tests were administered and peripheral blood samples taken. The study included 121 patients with AD, 94 with MCI, and 198 controls. Forty biallelic variants single nucleotide polimorphisms were genotyped in 8 genes related to reelin signaling pathway using a SNPlex genotyping system, and allele frequencies were compared between patients and controls using χ tests and obtaining odds ratios (OR). RESULTS: A total of 413 subjects with complete neuropsychological data were analyzed. A significant association between the genotypes RELN (rs528528 and rs2299356), PLK2 (rs15009 and rs702723), and CAMK2A (rs3756577 and rs3822606) and AD or MCI was found. A significant association also was found between the GG genotype at the RELN-rs2299356 and the risk of AD (OR=2.68, P=0.003) and between the AG genotype at the CAMK2A-rs3822606 (OR=2.13, P=0.004). We found a protective effect of the RELN-rs528528 CT genotype and MCI (OR=0.36, P=0.002), and the PLK2-rs15009 CC and GG genotypes and CC genotype at PLK2-rs702723 with OR ranging from 0.40 to 0.57 on AD. These data suggest that TT or CT genotypes at CAMK2A-rs3756577 is associated with risk reduction for AD and MCI ranging from 2 to nearly 8 times. CONCLUSIONS: Our data suggest a possible relation between certain reelin signaling pathway genotypes and cognitive impairment related to AD.

Alzheimer's disease: an evolutionary approach.

Alzheimer's disease (AD) is a complex disease associated with advanced age whose causes are still not fully known. Approaching the disease from an evolutionary standpoint may help in understanding the root cause of human vulnerability to the disease. AD is very common in humans and extremely uncommon in other mammals, which suggests that the genetic changes underlying the alterations in cerebral structure or function that have taken place over the course of the evolution of the genus Homo have left specific neurons in the human brain particularly vulnerable to factors which trigger the disease. Most of the genes whose mutation leads to AD are involved in synaptic plasticity. Evidence has also been found relating AD to neuronal oxidative stress. Neurons in certain association areas of the human brain retain juvenile characteristics into adulthood, such as the increased expression of genes related to synaptic activity and plasticity, incomplete myelination and elevated aerobic metabolism, which can cause an increase in oxidative stress in these neurons. Oxidative stress can cause myelin breakdown and epigenetic changes in the promoter region of genes related to synaptic plasticity, reducing their expression. These changes may in some cases induce hyperphosphorylation of tau and ß-amyloid deposits, which are characteristic of AD. The adaptation of humans to the cognitive niche probably required an increase in synaptic plasticity and activity and neuronal metabolism in neurons in areas related to certain cognitive functions such as autobiographical memory, social interaction and planning. The cost of these changes may have been the brain's increased vulnerability to factors which can trigger AD. This vulnerability may have resulted from the evolutionary legacies that have occurred over the course of the evolution of the human brain, making AD a possible example of antagonistic pleiotropy. The evolutionary approach allows apparently unrelated data from different disciplines to be combined in a manner that may lead to an improved understanding of complex diseases such as Alzheimer's.

Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course.

Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia.

Human neoteny revisited: The case of synaptic plasticity.

The process of learning requires morphological changes in the neuronal connections and the formation of new synapses. Due to the importance of memory and learning in our species, it has been suggested that the synaptic plasticity in a number of association areas is higher in the human brain than in other primates. Cortical neurons in mammals are characterized by higher metabolism, activity, and synaptic plasticity during development and the juvenile stage than in the adult. In Homo sapiens, brain development is retarded compared with other primates, especially in some association areas. These areas are characterized by the presence of neurons, which remain structurally immature throughout their lifespans and show an increase in the expression of the genes, which deal with metabolism and the activity and synaptic plasticity in adulthood. The retention of juvenile features in some adult neurons in our species has occurred in areas, which are related to episodic memory, planning, and social navigation. The increase of the aerobic metabolism in these neurons may lead, however, to higher levels of oxidative stress, therefore, favoring the development of neurodegenerative diseases which are exclusive, or almost exclusive, to humans, such as Alzheimer's disease.