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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Gustavsson, Anna Märta LU ; van Westen, Danielle LU ; Stomrud, Erik LU ; Engström, Gunnar LU ; Nägga, Katarina LU and Hansson, Oskar LU (2020) In Annals of Neurology 87(1). p.52-62
Abstract

Objective: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. Methods: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991–1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance... (More)

Objective: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. Methods: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991–1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009–2015). Results: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03–1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10–1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77–1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07–3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05–2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87–1.90] for Aβ42 and 1.35 [95% CI = 0.86–2.13] for Aβ42/p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. Interpretation: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. 

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of Neurology
volume
87
issue
1
pages
11 pages
publisher
John Wiley and Sons Inc.
external identifiers
  • pmid:31721283
  • scopus:85075725346
ISSN
0364-5134
DOI
10.1002/ana.25645
language
English
LU publication?
yes
id
ace92087-d873-44cb-bd7c-f28a76fbfa98
date added to LUP
2019-12-17 16:24:48
date last changed
2020-01-28 11:16:51
@article{ace92087-d873-44cb-bd7c-f28a76fbfa98,
  abstract     = {<p>Objective: To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. Methods: Participants comprised the cardiovascular cohort of the Swedish prospective population-based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991–1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β-amyloid<sub>42</sub> and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009–2015). Results: During 20 years of follow-up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all-cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03–1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10–1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77–1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3-graded score (adjusted HR = 1.90 [95% CI = 1.07–3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05–2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87–1.90] for Aβ<sub>42</sub> and 1.35 [95% CI = 0.86–2.13] for Aβ<sub>42</sub>/p-tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. Interpretation: Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. </p>},
  author       = {Gustavsson, Anna Märta and van Westen, Danielle and Stomrud, Erik and Engström, Gunnar and Nägga, Katarina and Hansson, Oskar},
  issn         = {0364-5134},
  language     = {eng},
  number       = {1},
  pages        = {52--62},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Annals of Neurology},
  title        = {Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia},
  url          = {http://dx.doi.org/10.1002/ana.25645},
  doi          = {10.1002/ana.25645},
  volume       = {87},
  year         = {2020},
}