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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia
Author(s) -
Gustavsson AnnaMärta,
Westen Danielle,
Stomrud Erik,
Engström Gunnar,
Nägga Katarina,
Hansson Oskar
Publication year - 2020
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25645
Subject(s) - dementia , medicine , hazard ratio , vascular dementia , odds ratio , prospective cohort study , hyperintensity , population , confidence interval , cohort , cardiology , magnetic resonance imaging , disease , radiology , environmental health
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 42 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 42 and 1.35 [95% CI = 0.86–2.13] for Aβ 42 /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. ANN NEUROL 2020;87:52–62