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- van de Pol, L. A., et al.
(author)
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White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study
- 2009
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In: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 80:10, s. 1069-1074
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Journal article (peer-reviewed)abstract
- Background: Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. Methods: This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. Results: Severity of MTA differed between MCI subtypes (p < 0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) Conclusion: We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.
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- Visser, P. J., et al.
(author)
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Development of screening guidelines and clinical criteria for predementia Alzheimer's disease
- 2008
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In: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 30:4, s. 254-265
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Journal article (peer-reviewed)abstract
- Background: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. Methods: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2 - 3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. Results: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.
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- Alafuzoff, Irina, et al.
(author)
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Beta-amyloid deposition in brains of subjects with diabetes
- 2009
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In: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 35:1, s. 60-68
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Journal article (peer-reviewed)abstract
- AIM:A causative association between diabetes mellitus (DM) and Alzheimer's disease (AD) has been suggested based on clinical and epidemiological studies. One hypothesis is that the link between DM and AD is related to the function of insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and pancreatic amylin but also beta-amyloid (Abeta). Thus, in diabetics, insulin and Abeta might compete for IDE and this might lead to an increase in Abeta. The objective of this study was to test the hypothesis that hyperinsulinaemia can elevate Abeta levels and thus contribute to AD pathology in humans.METHODS:Neuropathological examination was carried out employing conventional and immunohistochemical (IHC) methods of the brains obtained post mortem from 701 aged subjects.RESULTS:The loads of IHC/Abeta, silver stained neuritic plaques (NP) and neurofibrillary tangles (NFT) were significantly higher in subjects carrying the Apolipoprotein E e4 allele. In contrast, the loads of Abeta, NPs and NFT in the brains were not influenced by hyperglycaemia when comparing 134 diabetic with 567 non-diabetic subjects.CONCLUSIONS:We conclude that the hypothesis that hyperinsulinaemia would significantly elevate the Abeta load and thus increase the extent of AD pathology cannot be supported. Our result challenges the claim that DM is a direct risk factor of developing AD. Thus further studies on pathological lesions in demented diabetics should be conducted.
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- Håkansson, Krister, 1952-, et al.
(author)
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Association between mid-life marital status and cognitive function in later life : population based cohort study
- 2009
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In: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 339:July, s. Article number: b2462-
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Journal article (peer-reviewed)abstract
- Objectives To evaluate whether mid-life marital status is related to cognitive function in later life. Design Prospective population based study with an average follow-up of 21 years. Setting Kuopio and Joensuu regions in eastern Finland. Participants Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. Main outcome measures Alzheimer's disease and mild cognitive impairment. Results People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer's disease compared with married or cohabiting people. The highest increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. Conclusions Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.
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