Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

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T1 - Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

AU - Gustavsson, Anna Märta

AU - van Westen, Danielle

AU - Stomrud, Erik

AU - Engström, Gunnar

AU - Nägga, Katarina

AU - Hansson, Oskar

PY - 2020/1

Y1 - 2020/1

N2 - 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. 

AB - 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. 

UR - http://www.scopus.com/inward/record.url?scp=85075725346&partnerID=8YFLogxK

U2 - 10.1002/ana.25645

DO - 10.1002/ana.25645

M3 - Article

C2 - 31721283

AN - SCOPUS:85075725346

VL - 87

SP - 52

EP - 62

JO - Annals of Neurology

JF - Annals of Neurology

SN - 1531-8249

IS - 1

ER -