The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women

Aljondi, Rowa; Szoeke, Cassandra; Steward, Chris; Gorelik, Alexandra; Desmond, Patricia

doi:10.1007/s11682-018-9970-5

Cited by 32 publications

(28 citation statements)

References 70 publications

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“…Our MR results provide evidence for a protective role of HDL-C on ischemic SVD. This agrees with findings from two small observational studies: In the Women's Healthy Ageing Project, midlife HDL-C levels among 135 women were inversely associated with WMH volume after 20 years, independently of other vascular risk factors (Aljondi et al, 2018). Similarly, in a cross-sectional study of 817 participants F o r P e e r R e v i e w aged ≥50 years, higher HDL-C levels were cross-sectionally associated with lower volumes of both deep and periventricular WMH after adjusting for vascular risk factors (Yin et al, 2018).…”

Section: Discussionsupporting

confidence: 91%

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Georgakis

Malik

Anderson

et al. 2020

Brain

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Blood lipids are causally involved in the pathogenesis of atherosclerosis, but their role in cerebral small vessel disease remains largely elusive. Here, we explored associations of genetic determinants of blood lipid levels, lipoprotein particle components, and targets for lipid-modifying drugs with small vessel disease phenotypes. We selected genetic instruments for blood levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides, for cholesterol and triglycerides components of size-defined lipoprotein particles, and for lipid-modifying drug targets based on published genome-wide association studies (up to 617 303 individuals). Applying two-sample Mendelian randomization approaches we investigated associations with ischaemic and haemorrhagic manifestations of small vessel disease [small vessel stroke: 11 710 cases, 287 067 controls; white matter hyperintensities (WMH): 10 597 individuals; intracerebral haemorrhage: 1545 cases, 1481 controls]. We applied the inverse-variance weighted method and multivariable Mendelian randomization as our main analytical approaches. Genetic predisposition to higher HDL-C levels was associated with lower risk of small vessel stroke [odds ratio (OR) per standard deviation = 0.85, 95% confidence interval (CI) = 0.78–0.92] and lower WMH volume (β = –0.07, 95% CI = −0.12 to −0.02), which in multivariable Mendelian randomization remained stable after adjustments for LDL-C and triglycerides. In analyses of lipoprotein particle components by size, we found these effects to be specific for cholesterol concentration in medium-sized high-density lipoprotein, and not large or extra-large high-density lipoprotein particles. Association estimates for intracerebral haemorrhage were negatively correlated with those for small vessel stroke and WMH volume across all lipid traits and lipoprotein particle components. HDL-C raising genetic variants in the gene locus of the target of CETP inhibitors were associated with lower risk of small vessel stroke (OR: 0.82, 95% CI = 0.75–0.89) and lower WMH volume (β = −0.08, 95% CI = −0.13 to −0.02), but a higher risk of intracerebral haemorrhage (OR: 1.64, 95% CI = 1.26–2.13). Genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized high-density lipoprotein particles, is associated with both a lower risk of small vessel stroke and lower WMH volume. These analyses indicate that HDL-C raising strategies could be considered for the prevention of ischaemic small vessel disease but the net benefit of such an approach would need to be tested in a randomized controlled trial.

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Section: Discussionsupporting

confidence: 91%

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Georgakis

Malik

Anderson

et al. 2020

Brain

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“…27 In the present study, the ratio of WMH volume to ICV volume (WMHV : ICV; %) was used as an indicator of WMH enlargement. 31,32 Larger and smaller WMHV : ICV ratios were defined as those ≥0.257% (median) and <0.257%, respectively: the median value of the WMHV : ICV ratio was used to divide patients into 2 groups with minimal arbitrariness, because there has been no consensus on an appropriate cut-off value for elderly populations.…”

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confidence: 99%

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese　― The Hisayama Study ―

Yamasaki

Hata

Furuta

et al. 2020

Circ J

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Background: Both chronic kidney disease and brain white matter hyperintensities (WMH) are known to be risk factors of dementia and mortality. Methods and Results: In 2012, 1,214 community-dwelling Japanese subjects aged ≥65 years underwent brain magnetic resonance imaging (MRI) scans and a comprehensive health examination. This study investigated associations of the urinary albumin : creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with the WMH volume to intracranial volume (WMHV : ICV) ratio, and the association of the combination of UACR and the WMHV : ICV ratio with cognitive decline and mortality risk. The geometric mean of the WMHV : ICV ratio was 0.223% in the entire study population, and increased significantly with higher UACR levels after adjusting for potential confounding factors (0.213% for normoalbuminuria, 0.248% for microalbuminuria, and 0.332% for macroalbuminuria; Ptrend=0.01). In contrast, there was no clear association between eGFR and the WMHV : ICV ratio. Compared with subjects with normoalbuminuria and a smaller WMHV : ICV ratio (<0.257% [median]), subjects with albuminuria and a larger WMHV : ICV ratio (≥0.257%) had higher probabilities of cognitive decline at baseline and all-cause death during the follow-up. Conclusions: This study suggests that subjects with albuminuria have a greater risk of WMH enlargement and that the combination of albuminuria and WMH enlargement increases the risk of cognitive decline and all-cause mortality in an elderly Japanese population.

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“…Some previous longitudinal studies have examined the association between CVD risk level, calculated using multivariable risk factors, and cognitive impairment in amnestic and non-amnestic subtypes, and have reported contrasting results. Aljondi et al (2020) reported that a high FGCRS-based CVD risk level was associated with executive function but not with episodic memory, semantic memory, and visuospatial ability. Kaffashian et al (2013) showed that a high FGCRS-based CVD risk level was associated with faster cognitive decline in reasoning, phonemic fluency, semantic fluency, and vocabulary, but not with memory.…”

Section: Discussionmentioning

confidence: 99%

Absolute Cardiovascular Disease Risk Is Associated With the Incidence of Non-amnestic Cognitive Impairment in Japanese Older Adults

Makino

Lee

Bae

et al. 2021

Front. Aging Neurosci.

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BackgroundThe estimated absolute cardiovascular disease (CVD) risk level is known to be a useful surrogate marker for future cognitive impairment; however, evidence regarding its predictive validity in terms of cognitive subtypes is limited. We aimed to examine subtype-dependent differences in the associations between absolute CVD risk and the incidence of cognitive impairment in a community-dwelling older Japanese cohort.Methods and ResultsThis study comprised 1,641 cognitively intact older Japanese participants without CVDs at baseline. We estimated absolute CVD risk using WHO region-specific risk estimation charts and included age, sex, diabetes mellitus, smoking, systolic blood pressure, and total cholesterol at baseline, and the CVD risk level was stratified into the three following risk categories: low (<10%), moderate (10 to <20%), and high (≥20%). Objective cognitive screening was performed using a multicomponent neurocognitive test at baseline and follow-up, and the incidence of cognitive impairment over 48 ± 2 months was determined. The incidence of cognitive impairment in low-, moderate-, and high-CVD risk participants was 1.2, 3.0, and 5.4%, respectively, for amnestic subtypes and 5.8, 10.1, and 14.0%, respectively, for non-amnestic subtypes. After adjusting for potential confounding factors, the absolute CVD risk level was significantly associated with non-amnestic impairment but not with amnestic impairment.ConclusionsThe absolute CVD risk estimated using region-specific risk estimation charts in old age is useful to predict incidence of cognitive impairment. Strategies to screen populations at risk of cognitive impairment and to prevent progression to dementia should be cognitive subtype-specific.

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The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women

Cited by 32 publications

References 70 publications

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese　― The Hisayama Study ―

Absolute Cardiovascular Disease Risk Is Associated With the Incidence of Non-amnestic Cognitive Impairment in Japanese Older Adults

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The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women

Cited by 32 publications

References 70 publications

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Genetic determinants of blood lipids and cerebral small vessel disease: role of high-density lipoprotein cholesterol

Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese ― The Hisayama Study ―

Absolute Cardiovascular Disease Risk Is Associated With the Incidence of Non-amnestic Cognitive Impairment in Japanese Older Adults

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Association of Albuminuria With White Matter Hyperintensities Volume on Brain Magnetic Resonance Imaging in Elderly Japanese　― The Hisayama Study ―