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

Summary Multiple sclerosis (MS) is a neurological, demyelinating disorder with a putative autoimmune etiology. It is thought to be a multifactorial disease with a complex mode of inheritance. Here we report the results of a two-stage genomewide scan for loci predisposing to MS. The first stage of the screen, with a low-resolution map, was performed in a selection of 16 pedigrees collected from an isolated Finnish population. Multipoint, nonparametric linkage analysis of the 328 markers did not reveal statistically significant results. However, 10 slightly interesting regions ( P =.1–.15) emerged, including our previous findings of the HLA complex on 6p21 and a putative locus on 5p14-p12. Eight of these novel regions were further analyzed by use of denser marker maps, in the second stage of the scan. For the chromosomal regions 4cen, 11tel, and 17q, the statistical significance increased, but not conclusively; for 2q32 and 10q21, the statistical significance did not change. Accordingly, genotyping of the high-density markers in these regions was performed, and the data were analyzed by use of two-point, parametric linkage analysis using the complete pedigree information of the 21 Finnish multiplex families. We detected suggestive evidence for a predisposing locus on chromosomal region 17q22-q24. Several markers on 17q22-q24 yielded positive LOD scores, with the maximum LOD score ( Z max ) occurring with D17S807 ( Z max =2.8, θ=.04; dominant model. Interestingly, a suggestive linkage between MS and the markers on 17q22-q24 was also revealed by a recent genomewide scan in MS families from the United Kingdom.

Genomewide Scan of Multiple Sclerosis in Finnish Multiplex Families

A sample of 8,000 subjects to represent the population of Finland aged 30 years and over was used to identify patients with severe dementia; 141 cases were found. The prevalence of all types of severe dementia was 1.8% in the whole study population and 6.7% in the population aged 65 years and over. The prevalence increased with advancing age to 17.3% in the age group 85 years and over. Primary degenerative dementia constituted 50% of all cases; multi-infarct and combined dementia, 39%; and secondary dementia, 11%. Fifty-seven percent of the patients lived in institutions.

Prevalence of severe dementia in Finland.

Pfeiffer's Short Portable Mental Status Questionnaire (SPMSQ) is a brief screening test for organic brain syndromes. The validity of the SPMSQ was evaluated in a random sample of 119 community residents and 282 consecutively admitted medical inpatients. The SPMSQ proved to be a sensitive and specific screening test for moderate to severe dementia both in the community and hospital. Using the cut-off point (number of errors accepted) of three errors, the sensitivity of the test was 86.2% and the specificity 99.0% among medical inpatients. The percentages in the community sample were 66.7% and 100%, respectively. The validity of the SPMSQ was not as good for delirium because of its variable clinical picture. For screening purposes lower cut-off points than previously recommended should be used: three errors for dementia and two errors for delirium. Among Finnish elderly people it was not necessary to use correction for education in the SPMSQ.

Short Portable Mental Status Questionnaire as a screening test for dementia and delirium among the elderly.

Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.

A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.

• Two thousand consecutive patients aged 55 years and older admitted to a department of medicine in a large university hospital were examined for the presence of dementia. The occurrence of moderate and severe dementia was 9.1% for all age groups. It increased from 0.8% in the age group from 55 to 64 years to 31.2% in patients aged 85 years and older. Of the demented patients, 41.4% were delirious at admission, and 24.9% of all delirious patients were demented. Patients with vascular dementia constituted 72.4%, those with primary degenerative dementia 23.0%, and those with specific causes 4.6% of all demented patients. The mean hospitalization time for demented patients was significantly longer, and they needed significantly more daily nursing care, when compared with nondemented patients. (Arch Intern Med1986;146:1923-1926)

Juhani Wikström

Papers

Genomewide Scan of Multiple Sclerosis in Finnish Multiplex Families

Prevalence of severe dementia in Finland.

Short Portable Mental Status Questionnaire as a screening test for dementia and delirium among the elderly.

A putative vulnerability locus to multiple sclerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2.

Dementia among medical inpatients. Evaluation of 2000 consecutive admissions.