The idea of reserve against brain damage stems from the repeated observation that there does not appear to be a direct relationship between the degree of brain pathology or brain damage and the clinical manifestation of that damage. This paper attempts to develop a coherent theoretical account of reserve. One convenient subdivision of reserve models revolves around whether they envision reserve as a passive process, such as in brain reserve or threshold, or see the brain as actively attempting to cope with or compensate for pathology, as in cognitive reserve. Cognitive reserve may be based on more efficient utilization of brain networks or of enhanced ability to recruit alternate brain networks as needed. A distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged. Epidemiologic and imaging data that help to develop and support the concept of reserve are presented.

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What is cognitive reserve? Theory and research application of the reserve concept.

国際生活機能分類(International Classification of Functioning, Disability and Health: ICF)にみた福祉・保健・医療の専門職協働における連携に関する貢献と課題

Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Geneticists have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits—describing the methods, limitations, and recent applications to biological problems.

Genetic Dissection of Complex Traits

Prevalence of Alzheimer's Disease in a Community Population of Older Persons

Clinically diagnosed Alzheimer's disease and other dementing illnesses were assessed in a geographically defined US community. Of 3623 persons (80.8% of all community residents over 65 years of age) who had brief memory testing in their homes, a stratified sample of 467 persons underwent neurological, neuropsychological, and laboratory examination. Prevalence rates of Alzheimer's disease were calculated for the community population from the sample undergoing clinical evaluation. Of those over the age of 65 years, an estimated 10.3% (95% confidence limits, 8.1% and 12.5%) had probable Alzheimer's disease. This prevalence rate was strongly associated with age. Of those 65 to 74 years old, 3.0% (95% confidence limits, 0.8 and 5.2) had probable Alzheimer's disease, compared with 18.7% (95% confidence limits, 13.2 and 24.2) of those 75 to 84 years old and 47.2% (95% confidence limits, 37.0 and 63.2) of those over 85 years. Other dementing conditions were uncommon. Of community residents with moderate or severe cognitive impairment, 84.1% had clinically diagnosed Alzheimer's disease as the only probable diagnosis. These data suggest that clinically diagnosed Alzheimer's disease is a common condition and that its public health impact will continue to increase with increasing longevity of the population. (JAMA. 1989;262:2551-2556)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=379351&pdfFileName=jama_262_18_036.pdf

Prevalence of Alzheimer's Disease in a Community Population of Older Persons: Higher Than Previously Reported

Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis

The frequency of malignant diseases among 1866 living and 340 deceased multiple sclerosis (MS) patients was investigated in Finland. The study revealed a low prevalence (0.64%) and mortality (0.07%) rate of cancer among MS patients. The difference between MS patients and general population was significant. The highest rate was found in the group from 40 to 49 years while in the general population the rate of cancer among MS patients tended to fall after the age of 50. The possible role of selenium, one of the antioxidants in the pathogenesis of MS and cancer, is discussed because recent data have shown a very high negative correlation between selenium and cancer death rates.

Malignant diseases among patients with multiple sclerosis

Although association between multiple sclerosis (MS) and HLA-DR2, DQw6 has been well documented, family studies have not established linkage to HLA. Here we have (1) carried out an HLA-DQA1, -DQB1 association study in unrelated patients and controls, and (2) analyzed linkage between MS and HLA in multiplex families using both nonparametric and parametric methods. The subjects and families were derived from the genetically homogeneous Finnish population, and 14 of the 21 families came from a high-risk area with exceptional familial clustering of cases. In the association study, the frequencies of the alleles DQA1*0102 and DQB1*0602 (encoding DR2-associated DQw6 antigen) were significantly increased in MS patients compared to controls. In the families, we observed that the segregation of MS with DQA1*0102 and DQB1*0602 was not HLA haplotype specific, i.e., these alleles were frequently transmitted to MS relatives on different parental haplotypes. Consequently, we found strong evidence for linkage between MS and HLA only when the haplotype-independent segregation of the MS-associated alleles was controlled. This observation may partially explain the lack of linkage evidence in previous family studies. The highest LOD scores were obtained to the DQA1 locus (LODmax = 6.43, θ = 0.00). The linkage analyses suggest that both the patients’ HLA haplotypes may contribute to MS susceptibility. In one of a patient’s haplotypes, the susceptibility locus was closely associated with DQA1*0102 and DQB1*0602, whereas in the other haplotype no association with any of the individual candidate loci was found. These results demonstrate, for the first time, a close linkage between MS and HLA, and raise the possibility of distinct HLA-linked susceptibility genes in MS.

Reappraisal of HLA in multiple sclerosis: close linkage in multiplex families.

Further studies on the epidemiology of multiple sclerosis (MS) in Finland were carried out in three different types of geographical unit: in counties, combined clerical districts, and single clerical districts. For longitudinal studies, the prevalence of MS by present domicile was compared to that by place of birth, and also to the number of MS cases in relation to the number of births. The analysis was based on 1,866 living MS patients. The highest prevalence by present domicile was recorded in the southwestern county of Turku and Pori (52.3 cases per 100,000 inhabitants). It was 39.6 for the whole country. Two separate clusters were found at the level of combined and single clerical districts: one in the western county of Vaasa, and another in the south-western county of Turku and Pori. The highest prevalences by present domicile were found in two clerical districts of Vaasa (83.5 and 79.7). They also had very high prevalences by place of birth. They lie close to each other, but are not immediate neighbours. Another high-risk focus was revealed in an area of the neighbouring districts of Turku and Pori. In fact, the two highest prevalences by place of birth were found in this region (123.1 and 95.0). The focus extended from the coastal area to the more central region of the county, and further to the western districts of the otherwise medium-risk county of Hame. Thus, two separate foci were found in Finland: one in the western and another in the southwestern part of the country. The clustering became even more pronounced when the prevalences by place of birth were analysed. Considering that the Finnish population still largely originates from genetic isolates of varying degrees, gene enrichment explains the clustering at least partly.

Juhani Wikström

Papers

Intercellular adhesion molecule-1 K469E polymorphism: study of association with multiple sclerosis

Malignant diseases among patients with multiple sclerosis

Reappraisal of HLA in multiple sclerosis: close linkage in multiplex families.

Studies on the clustering of multiple sclerosis in Finland I: Comparison between the domiciles and places of birth in selected subpopulations.

Golli-MBP gene in multiple sclerosis susceptibility