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Risk factors for development of neurocognitive disorders

Gustavsson, Anna-Märta LU (2019) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2019(30).
Abstract
Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer’s disease (AD) and vascular dementia. The aim of this thesis was to study if risk factors affect key brain pathology directly, by using biomarkers for dementia in preclinical stages, and to assess previous findings in a large population-based setting.

Paper I: arterial stiffness was not cross-sectionally related to cognitive performance or presence of cerebral microbleeds, and microbleeds did not affect cognitive performance in cognitively healthy elderly (n=208, mean age 72 years). There was a trend towards an association between arterial stiffness and white matter... (More)
Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer’s disease (AD) and vascular dementia. The aim of this thesis was to study if risk factors affect key brain pathology directly, by using biomarkers for dementia in preclinical stages, and to assess previous findings in a large population-based setting.

Paper I: arterial stiffness was not cross-sectionally related to cognitive performance or presence of cerebral microbleeds, and microbleeds did not affect cognitive performance in cognitively healthy elderly (n=208, mean age 72 years). There was a trend towards an association between arterial stiffness and white matter hyperintensities.

Paper II: increased levels of triglycerides and cholesterol in midlife (mean age 54
years) were independently associated with AD biomarkers (β-amyloid and tau) 20 years later, in 318 individuals who were cognitively healthy at follow-up (mean age 73 years).

Paper III: higher physical activity in midlife (assessed twice, mean age 58 and 63 years) was independently associated with reduced risk of incident vascular dementia (n=300) during 14 years of follow-up in a population-based cohort (n=20 639). No association between physical activity and incident all-cause dementia (n=1375) or AD (n=834) was found.

Paper IV: ultrasound markers of atherosclerosis measured in midlife (mean age 58 years) were associated with incident vascular dementia (n=109) and all-cause dementia (n=462), but not with AD (n=285) during 20 years of follow-up in a population-based cohort (n=6103). In a cognitively healthy subcohort (n=330), midlife atherosclerosis (mean age 54 years) was associated with cerebral small vessel disease, but not with AD biomarkers at follow-up (mean age 73 years).

These findings suggest that midlife dyslipidaemia may be directly related to brain AD pathology, whereas arterial stiffness, physical activity, and atherosclerosis seem to be primarily related to cerebrovascular disease. (Less)
Abstract (Swedish)
Abstract
Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer’s disease (AD) and vascular dementia. The aim of this thesis was to study if risk factors
affect key brain pathology directly, by using biomarkers for dementia in preclinical stages, and to assess previous findings in a large population-based setting.

Paper I: arterial stiffness was not cross-sectionally related to cognitive performance or presence of cerebral microbleeds, and microbleeds did not affect cognitive performance in cognitively healthy elderly (n=208, mean age 72 years). There was a trend towards an association between arterial stiffness and white matter... (More)
Abstract
Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer’s disease (AD) and vascular dementia. The aim of this thesis was to study if risk factors
affect key brain pathology directly, by using biomarkers for dementia in preclinical stages, and to assess previous findings in a large population-based setting.

Paper I: arterial stiffness was not cross-sectionally related to cognitive performance or presence of cerebral microbleeds, and microbleeds did not affect cognitive performance in cognitively healthy elderly (n=208, mean age 72 years). There was a trend towards an association between arterial stiffness and white matter hyperintensities.

Paper II: increased levels of triglycerides and cholesterol in midlife (mean age 54 years) were independently associated with AD biomarkers (ß-amyloid and tau) 20 years later, in 318 individuals who were cognitively healthy at follow-up (mean age 73 years).

Paper III: higher physical activity in midlife (assessed twice, mean age 58 and 63 years) was independently associated with reduced risk of incident vascular dementia (n=300) during 14 years of follow-up in a population-based cohort
(n=20 639). No association between physical activity and incident all-cause dementia (n=1375) or AD (n=834) was found.

Paper IV: ultrasound markers of atherosclerosis measured in midlife (mean age 58 years) were associated with incident vascular dementia (n=109) and all-cause dementia (n=462), but not with AD (n=285) during 20 years of follow-up in a
population-based cohort (n=6103). In a cognitively healthy subcohort (n=330) midlife atherosclerosis (mean age 54 years) was associated with cerebral small vessel disease, but not with AD biomarkers at follow-up (mean age 73 years).

These findings suggest that midlife dyslipidaemia may be directly related to brain AD pathology, whereas arterial stiffness, physical activity, and atherosclerosis seem to be primarily related to cerebrovascular disease. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Kivipelto, Miia, Karolinska Institutet, Stockholm
organization
alternative title
Riskfaktorer för kognitiva sjukdomar
publishing date
type
Thesis
publication status
published
subject
keywords
vascular risk factors, dementia, Alzheimer’s disease, ß-amyloid, white matter hyperintensities, cerebral small vessel disease
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2019
issue
30
pages
81 pages
publisher
Lund University: Faculty of Medicine
defense location
Lilla aulan, Jan Waldenströms gata 5, Skånes Universitetssjukhus i Malmö
defense date
2019-04-12 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-759-2
language
English
LU publication?
yes
id
f0016d24-9cd2-4496-93da-7ecabfed32ad
date added to LUP
2019-03-22 11:15:37
date last changed
2019-11-19 13:49:47
@phdthesis{f0016d24-9cd2-4496-93da-7ecabfed32ad,
  abstract     = {Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer’s disease (AD) and vascular dementia. The aim of this thesis was to study if risk factors affect key brain pathology directly, by using biomarkers for dementia in preclinical stages, and to assess previous findings in a large population-based setting.<br/><br/>Paper I: arterial stiffness was not cross-sectionally related to cognitive performance or presence of cerebral microbleeds, and microbleeds did not affect cognitive performance in cognitively healthy elderly (n=208, mean age 72 years). There was a trend towards an association between arterial stiffness and white matter hyperintensities.<br/><br/>Paper II: increased levels of triglycerides and cholesterol in midlife (mean age 54<br/>years) were independently associated with AD biomarkers (β-amyloid and tau) 20 years later, in 318 individuals who were cognitively healthy at follow-up (mean age 73 years).<br/><br/>Paper III: higher physical activity in midlife (assessed twice, mean age 58 and 63 years) was independently associated with reduced risk of incident vascular dementia (n=300) during 14 years of follow-up in a population-based cohort (n=20 639). No association between physical activity and incident all-cause dementia (n=1375) or AD (n=834) was found.<br/><br/>Paper IV: ultrasound markers of atherosclerosis measured in midlife (mean age 58 years) were associated with incident vascular dementia (n=109) and all-cause dementia (n=462), but not with AD (n=285) during 20 years of follow-up in a population-based cohort (n=6103). In a cognitively healthy subcohort (n=330), midlife atherosclerosis (mean age 54 years) was associated with cerebral small vessel disease, but not with AD biomarkers at follow-up (mean age 73 years).<br/><br/>These findings suggest that midlife dyslipidaemia may be directly related to brain AD pathology, whereas arterial stiffness, physical activity, and atherosclerosis seem to be primarily related to cerebrovascular disease.},
  author       = {Gustavsson, Anna-Märta},
  isbn         = {978-91-7619-759-2},
  issn         = {1652-8220},
  language     = {eng},
  number       = {30},
  publisher    = {Lund University: Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Risk factors for development of neurocognitive disorders},
  url          = {https://lup.lub.lu.se/search/ws/files/62056116/Risk_factors_for_development_of_neurocognitive_disorders_A_M_Gustavsson.pdf},
  volume       = {2019},
  year         = {2019},
}