Risk factors for development of neurocognitive disorders

Anna-Märta Gustavsson

Risk factors for development of neurocognitive disorders

Research output: Thesis › Doctoral Thesis (compilation)

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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 (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.

Translated title of the contribution	Riskfaktorer för kognitiva sjukdomar
Original language	English
Qualification	Doctor
Awarding Institution	Department of Clinical Sciences, Malmö
Supervisors/Advisors	Nägga, Katarina, Supervisor Hansson, Oskar, Assistant supervisor Abul-Kasim, Kasim, Assistant supervisor Nilsson, Peter M, Assistant supervisor
Award date	2019 Apr 12
Place of Publication	Lund
Publisher	Lund University: Faculty of Medicine
ISBN (Print)	978-91-7619-759-2
Publication status	Published - 2019

Bibliographical note

Defence details
Date: 2019-04-12
Time: 09:00
Place: Lilla aulan, Jan Waldenströms gata 5, Skånes Universitetssjukhus i Malmö
External reviewer(s)
Name: Kivipelto, Miia
Title: professor
Affiliation: Karolinska Institutet, Stockholm

Subject classification (UKÄ)

Clinical Medicine

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Risk factors for development of neurocognitive disorders A-M GustavssonFinal published version, 1.93 MB

2 Article

Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later
Nägga, K., Gustavsson, A.-M., Stomrud, E., Lindqvist, D., van Westen, D., Blennow, K., Zetterberg, H., Melander, O. & Hansson, O., 2018 Jan 2, In: Neurology. 90, 1, p. 1-11
Research output: Contribution to journal › Article › peer-review

Open Access
Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness.
Gustavsson, A.-M., Stomrud, E., Abul-Kasim, K., Minthon, L., Nilsson, P., Hansson, O. & Nägga, K., 2015, In: Cerebrovascular Diseases Extra. 5, 2, p. 41-51
Research output: Contribution to journal › Article › peer-review

Open Access
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title = "Risk factors for development of neurocognitive disorders",

abstract = "Vascular risk factors are believed to be involved in dementia development by increasing risk of the most common dementia types, Alzheimer{\textquoteright}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 54years) 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.",

keywords = "vascular risk factors, dementia, Alzheimer{\textquoteright}s disease, {\ss}-amyloid, white matter hyperintensities, cerebral small vessel disease",

author = "Anna-M{\"a}rta Gustavsson",

note = "Defence details Date: 2019-04-12 Time: 09:00 Place: Lilla aulan, Jan Waldenstr{\"o}ms gata 5, Sk{\aa}nes Universitetssjukhus i Malm{\"o} External reviewer(s) Name: Kivipelto, Miia Title: professor Affiliation: Karolinska Institutet, Stockholm ",

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series = "Lund University, Faculty of Medicine Doctoral Dissertation Series",

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T1 - Risk factors for development of neurocognitive disorders

AU - Gustavsson, Anna-Märta

N1 - Defence details Date: 2019-04-12 Time: 09:00 Place: Lilla aulan, Jan Waldenströms gata 5, Skånes Universitetssjukhus i Malmö External reviewer(s) Name: Kivipelto, Miia Title: professor Affiliation: Karolinska Institutet, Stockholm

PY - 2019

Y1 - 2019

N2 - 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 54years) 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.

AB - 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 54years) 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.

KW - vascular risk factors

KW - dementia

KW - Alzheimer’s disease

KW - ß-amyloid

KW - white matter hyperintensities

KW - cerebral small vessel disease

M3 - Doctoral Thesis (compilation)

SN - 978-91-7619-759-2

VL - 2019:30

T3 - Lund University, Faculty of Medicine Doctoral Dissertation Series

PB - Lund University: Faculty of Medicine

CY - Lund

ER -

Risk factors for development of neurocognitive disorders

Abstract

Bibliographical note

Subject classification (UKÄ)

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Research output

Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness.

Cite this