CV Risk Linked to Dementia, Brain Lesions Early and Late in Life

Megan Brooks

August 22, 2018

Two new studies provide more evidence that cardiovascular (CV) health is important to brain health throughout life.

One study found that increasing numbers of optimal CV health measures, such as normal weight, blood pressure, cholesterol, and blood glucose, were associated with a lower risk for dementia and cognitive decline in adults aged 65 years and older.

The other study found that healthy lifestyle factors in young adulthood correlated with a higher density of blood vessels in the brain, higher brain blood flow, and fewer white matter hyperintensity (WMH) lesions, which have been associated with a higher risk for stroke and dementia in later life.

Both studies appear in the August 21 issue of JAMA.

These two studies "convey an immediately actionable message to clinicians, policy makers, and patients," write Jeffrey Saver, MD, from the University of California at Los Angeles and JAMA associate editor, and Mary Cushman, MD, from University of Vermont, Burlington, in an accompanying editorial.   

"Available evidence indicates that to achieve a lifetime of robust brain health free of dementia, it is never too early or too late to strive for attainment of ideal cardiovascular health," they conclude.

French Longitudinal Study

In one report, Cécilia Samieri, PhD, from the University of Bordeaux, France, and colleagues investigated the association between CV health level and risk for dementia and cognitive decline in 6626 community-dwelling older adults (63.4% women; mean age, 73.7 years at inception) participating in the French Three-City (3C) Study, a prospective cohort study examining vascular risk factors for cognitive impairment and dementia.

They defined CV health by using the American Heart Association (AHA) Life's Simple 7 metrics, specifically nonsmoking status, physical activity at goal level, body mass index less than 25 kg/m2, healthy diet consistent with current guidelines, untreated blood pressure less than 120 mm Hg/less than 80 mm Hg, untreated total cholesterol less than 200 mg/dL, and fasting blood glucose less than 100 mg/dL.

At baseline, 2412 (36.5%) participants had 0 to 2 health metrics at optimal levels, while 3781 (57.1%) had 3 to 4 and 433 (6.5%) had 5 to 7 health metrics at optimal levels. During a mean follow-up duration of 8.5 years, 745 participants developed dementia.

Among individuals with poorer CV health at baseline, defined as 0 to 2 optimal metrics, 13.3 of every 100 developed dementia, compared with 7.1 of every 100 who had more favorable CV status (5 to 7 optimal metrics), Samieri and colleagues report.    

In multivariable models, an increased number of optimal CV health metrics was significantly associated with lower risk for dementia (hazard ratio, 0.90 for each additional metric at recommended optimal level; 95% confidence interval [CI], 0.84 - 0.97).

"Importantly, while achieving the seven cardiovascular health factors at optimal levels is certainly the ideal target, this study shows that any additional factor at optimal level decreases the risk of dementia (by 10%)," Samieri told Medscape Medical News.

"Furthermore, even more subtle changes from poor to intermediate levels also decreased dementia risk in this study. From a pragmatic and public health perspective, promoting change in cardiovascular health from poor to intermediate levels may be more achievable and have a greater population-level effect than the more challenging change from poor to optimal levels," said Samieri.

The researchers say a limitation of the study is that CV health metrics were assessed only at baseline, so the effects of their evolution and treatment over time on cognitive outcomes could not be explored. Also, the mainly white and urban study population may not be fully generalizable to other racial-ethnic and sociocultural groups.

Novel Imaging Data

Added support linking CV health to brain health comes from a neuroimaging study looking at the association of modifiable CV risk factors with cerebrovascular structure and function and WMH in 125 young adults (mean age, 25 years; 49% women) without evidence of cerebrovascular disease.

In this cross-sectional study, a higher number of optimal CV health metrics was correlated with higher cerebral vessel density, higher cerebral blood flow, and fewer WMH lesions, Paul Leeson, PhD, from the University of Oxford, John Radcliffe Hospital, United Kingdom, and colleagues report.    

For each additional risk factor categorized as healthy:

  • Vessel density was greater by 0.3 vessels/cm3 (95% CI, 0.1 - 0.5; P = .003);

  • Vessel caliber was greater by 8 μm (95% CI, 3 - 13; P = .01); and

  • WMH lesions were fewer by 1.6 lesions (95% CI, −3.0 to −0.5; P = .006).

Among the 52 participants with available data, cerebral blood flow varied with vessel density and was 2.5 mL/100 g/min higher for each healthier category of a modifiable risk factor (95% CI, 0.16 - 4.89; P = .03).

"We were able to show that there are differences in the blood vessels related to levels of different risk factors and that these changes are evident in young adulthood" in the absence of cerebrovascular disease, Leeson told Medscape Medical News. "Therefore, making healthy life choices during young adulthood may be having a direct benefit to how the brain functions during young adulthood."  

Degree of Precision

In their editorial, Saver and Cushman note that some features assessed in this trial are "staples" of the clinical imaging evaluation of the brain and brain vasculature, including cerebral perfusion measures and extent of brain WMH. "However, these parameters have not previously been evaluated with this degree of precision in a large cohort of young, healthy individuals," they note.

The study also used novel magnetic resonance "vesselness-imaging" techniques only recently available to assess morphologic features of the cerebral vasculature, including brain vessel density, brain vessel caliber, and brain vessel tortuosity.

"Failure to attain optimal cardiovascular health appears to subtly compromise the fundamental anatomic structure of the brain vascular system in addition to its functional physiology and the integrity of the brain tissue it nourishes," write Saver and Cushman.

They caution, however, that both studies were observational, so they indicate correlation and association, not causation, and unmeasured and residual confounding is possible.

"Proof of causation requires supportive findings from randomized studies, but completed trials assessing interventions to improve cardiovascular health factors, which have to date shown variable results on cognitive outcomes, have generally been too small and too short in duration to provide definitive guidance," they write.

The 3C study is conducted under a partnership agreement between INSERM, the ISPED of the University of Bordeaux, and Sanofi-Aventis. Samieri has disclosed no relevant financial relationships. Funding for the imaging study was provided by a British Heart Foundation (BHF), the Oxford BHF Centre for Research Excellence, and the National Institute for Health Research Oxford Biomedical Research Centre. Leeson has disclosed no relevant financial relationships.

JAMA. 2018;320:657-664, 665-673, 645-647. Samieri et al abstractLeeson et al abstract, Editorial

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