Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Gustavsson, Anna‐Märta; Westen, Danielle van; Stomrud, Erik; Engström, Gunnar; Nägga, Katarina; Hansson, Oskar

doi:10.1002/ana.25645

Cited by 52 publications

(45 citation statements)

References 37 publications

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“…In multivariate adjusted analyses, only serum cholesterol was significantly associated with dementia with vascular features, whereas none of the midlife vascular risk factors were related to pure AD-findings supporting the Swedish study. 1 The relationship of midlife cholesterol that was specific to vascular-type dementia may also shed light on the results of a further recent study 5 using Mendelian randomization (MR); in agreement with observational findings, genes encoding targets of several lipid-lowering drug classes were not related to diagnosis of AD (not separating pure and mixed types) in people aged 70 years and older. Further explanation may be selection bias associated with MR studies, especially for earlier and later developing health conditions that have shared etiology.…”

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confidence: 55%

Vascular and Alzheimer Disease in Dementia

Strandberg

Tienari

Kivimäki

2020

Annals of Neurology

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Gustavsson et al 1 recently showed that midlife atherosclerosis is related to vascular dementia and small vessel disease but not to Alzheimer-type dementia (AD) in the Swedish population-based Malmö Diet and Cancer Study. Although AD is frequently cited as the most common type of dementia, the relative contributions of vascular and neurodegenerative pathology to clinical dementia have not been clear. These separations are, however, important because they have direct implications for prevention. Although "pure" AD still defies causal treatment, there are possibilities for vascular prevention.We have earlier compared results from a systematic review of studies reporting clinicopathological data of dementia cases 2 and detailed death records of vascular comorbidity with dementia in the 49-year follow-up of older men (Helsinki Businessmen Study [HBS]). 3 This comparison 4 suggested that pure AD would comprise only one-quarter of all dementia cases in older age. The proportions of "pure" vascular dementia in neuropathological studies (26%) and vascular dementia in the HBS (22.5%) were also quite close. We have now added data from dementia types in the Swedish study, and the distributions show remarkable similarity (Table).In the HBS, we examined dementia diagnosis in older age in relation to vascular risk factors measured in midlife, at a median age of 42 years. In multivariate adjusted analyses, only serum cholesterol was significantly associated with dementia with vascular features, whereas none of the midlife vascular risk factors were related to pure AD-findings supporting the Swedish study. 1 The relationship of midlife cholesterol that was specific to vascular-type dementia may also shed light on the results of a further recent study 5 using Mendelian randomization (MR); in agreement with observational findings, genes encoding targets of several lipid-lowering drug classes were not related to diagnosis of AD (not separating pure and mixed types) in people aged 70 years and older. Further explanation may be selection bias associated with MR studies, especially for earlier and later developing health conditions that have shared etiology.

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mentioning

confidence: 55%

Vascular and Alzheimer Disease in Dementia

Strandberg

Tienari

Kivimäki

2020

Annals of Neurology

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“…45 We hypothesize that a composite measure of vascular risks may have a stronger relationship with clinical and cognitive outcomes because vascular risks have more widespread effects on the brain, including WMH burden, white matter integrity, brain atrophy, and infarcts, among others. 4,53,54 Although we did not examine interactions between AD and CVD, we further hypothesize that CVD may lower the threshold for the impact of AD on cognition, given recent findings from this and other cohorts that AD and CVD appear independently associated with the risk of MCI 55 and cognitive decline 56 (also see 57,58).…”

Section: Discussionmentioning

confidence: 97%

Cognitive reserve and midlife vascular risk: Cognitive and clinical outcomes

Soldan

Pettigrew

Zhu

et al. 2020

Ann Clin Transl Neurol

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Objective Examine whether cognitive reserve moderates the association of 1) vascular risk factors and 2) white matter hyperintensity burden with risk of clinical progression and longitudinal cognitive decline. Methods BIOCARD Study participants were cognitively normal and primarily middle‐aged (M = 57 years) at baseline and have been followed with annual cognitive and clinical assessments (M = 13 years). Baseline cognitive reserve was indexed with a composite score combining education with reading and vocabulary scores. Baseline vascular risk (N = 229) was assessed with a composite risk score reflecting five vascular risk factors. Baseline white matter hyperintensity load (N = 271) was measured with FLAIR magnetic resonance imaging. Cox regression models assessed risk of progression from normal cognition to onset of clinical symptoms of Mild Cognitive Impairment. Longitudinal mixed effects models measured the relationship of these variables to cognitive decline, using a global composite score, and executive function and episodic memory sub‐scores. Results Both vascular risk and white matter hyperintensities were associated with cognitive decline, particularly in executive function. Higher vascular risk, but not white matter hyperintensity burden, was associated with an increased risk of progression to Mild Cognitive Impairment. Higher cognitive reserve was associated with a reduced risk of symptom onset and higher levels of baseline cognition but did not modify the associations between the vascular risk score and white matter hyperintensities with clinical progression or cognitive decline. Interpretation Although cognitive reserve has protective effects on clinical and cognitive outcomes, it does not mitigate the negative impact of vascular risk and small vessel cerebrovascular disease on these same outcomes.

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“…In concordance, a specific pathway between long sleep duration and cognitive decline is not known. Long sleep duration is associated with cerebrovascular disease 43,44 which is a contributor to cognitive impairment and cognitive decline 45,46 . Persons with cardiovascular disease have more often problems in maintaining sleep 47,48 .…”

Section: Discussionmentioning

confidence: 99%

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

Brachem

Winkler

Tebrügge

et al. 2020

Sci Rep

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Associations of sleep characteristics with mild cognitive impairment (Mci) have been examined in cross-sectional, but rarely in longitudinal studies. incident Mci and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a populationbased cohort study in Germany (age at first follow-up 50−80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including pSQi (pittsburgh Sleep Quality index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing Mci when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. poor sleep quality (pSQi > 5) (RR = 1.43, 95% CI: 1.12−1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94−2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed. Dementia is a growing public health burden worldwide. In 2013 an estimated 44.35 million persons had a prevalent dementia 1. By 2050 it is expected that this number triples to 135.46 million prevalent dementia cases 2,3. Because no effective causal medical therapies are available for dementia, primary prevention of dementia and of its early precursors is the most promising option currently available to cap the rising prevalence 4,5. Subjects with mild cognitive impairment (MCI) have an increased risk of progression to Alzheimer's disease (AD) and other forms of dementia. Therefore, identification of modifiable risk factors for incident MCI is important, and poor sleep is considered a potential risk factor for cognitive decline and disease progression 6-13. Sleep characteristics were suggested as modifiable risk factors for cognitive decline, for example by influencing hippocampal volume 14,15. Two up-to-date reviews on this relationship indicate an association between cognitive decline and sleep problems, such as poor sleep quality, short or long sleep duration, and sleep disturbances 12,16. However, both reviews concluded that there is still a need for long term prospective studies to ensure that sleep problems precede cognitive decline 12,16. Two recently published cohort studies on sleep characteristics and dementia were not included in these reviews 17,18. Both suggest that self-reported long sleep duration as well as self-reported sleep disturbances increase the risk of dementia. Additionally, Jackowska and Cadar 19 found an association between decreased cognitive function and self-reported long and short sleep duration in their

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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Cited by 52 publications

References 37 publications

Vascular and Alzheimer Disease in Dementia

Vascular and Alzheimer Disease in Dementia

Cognitive reserve and midlife vascular risk: Cognitive and clinical outcomes

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

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