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, non-parametric 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 (Zmax) occurring with D17S807 (Zmax = 2.8, theta = .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.

SUMMARY Brains from a prospective study of demented patients were investigated post mortem. Of the 27 patients with clinical diagnosis of vascular dementia, 23 showed multiple cerebral infarcts but senile plaques and neurofibrillary tangles were absent or in insignificant numbers. This gives an accuracy of 85%, a figure higher than previously documented.The two most common causes of dementia are Alzheimer's disease and widespread ischaemic lesions of the brain, commonly referred to as multi-infarct dementia (MID).1 2 Dementia may also be due to a combination of these two conditions,34 and to a number of other disorders.5Few studies have been published on the accuracy of the clinical diagnosis of these diseases as verified post mortem.6-12 For Alzheimer's disease the accuracy has varied from 52 to 85%6-12 and for multi-infarct dementia from 21 to 82%.6-8 10 11 The low accuracy of the clinical diagnosis of multi-infarct dementia has led researchers to question the reliability of its antemortem diagnosis.'3 14 We carried out a post mortem neuropathological investigation of demented patients admitted to departments of internal medicine and neurology. The patients had all been subjected to extensive clinical investigations, including psychometric analysis and computed tomography of the head (CT). The value of CT scans and ischaemic scores4 15 in the differential diagnosis between Alzheimer's disease and multiinfarct dementia was also investigated. Patients and methods Clinical evaluationThis prospective study is a follow-up of 233 consecutively admitted patients recruited from a study on

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.

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Previous surveys in Finland from the 1960s have documented an uneven geographic distribution of multiple sclerosis (MS). In the present study, the incidence of MS was studied during 1979–1993 in the western Vaasa and Seinäjoki regions and in southern Uusimaa. The overall difference between the western and southern regions persisted; 8.7 per 100,000 in the western, and 5.1 per 100,000 in the southern region. The incidence of 11.6 per 100,000 in Seinäjoki was more than twofold greater than the 5.2 per 100,000 incidence found in neighboring Vaasa. An increasing incidence trend was observed for men in Seinäjoki, and a decrease for both sexes in Vaasa, while in Uusimaa the incidence remained stable for both sexes. The different incidence trends could not be readily explained by differences in case ascertainment but suggest the effect of environmental factors that have modulated the incidence of MS during the 15-year study period.