Risk also associated with brain volume measures

A points-based cardiovascular risk score paralleled cognitive decline, a study of older adults found.

Over a median 5.8 year follow-up, baseline Framingham General Cardiovascular Risk Scores (FGCRS) — summed points based on age, sex, smoking, systolic blood pressure, medication for hypertension, total cholesterol, HDL cholesterol, and diabetes — showed that compared with the lowest risk tertile, those who scored in the highest tertile had faster declines in:

  • Global cognition (beta −0.019; 95% CI −0.035 to −0.003).
  • Episodic memory (beta −0.023; 95% CI −0.041 to −0.004).
  • Working memory (beta −0.021; 95% CI −0.035 to −0.007).
  • Perceptual speed (beta −0.027; 95% CI −0.042 to −0.011).

The highest risk tertile was also associated with smaller volumes of the hippocampus, gray matter, and total brain, and with greater volume of white matter hyperintensities (WMH), wrote Weili Xu, PhD, of Tianjin Medical University in China, and coauthors in the Journal of the American College of Cardiology. Stratified analysis showed the effects were most prominent in non-carriers of the APOE e4 allele.

“The findings on the association of higher FGCRS with cognitive decline in episodic memory, working memory, and perceptual speed suggest that higher cardiovascular burden might have effects on both neurodegenerative and vascular changes,” Xu and coauthors wrote.

In an accompanying editorial, Costantino Iadecola, MD, and Neal S. Parikh, MD, MS, both of Weill Cornell Medicine in New York City, wrote that the study “augmented the clinical usefulness of the FGCRS, broadening its ability to assess the risk of critical outcomes beyond cardiovascular disease.”

“In both continuous and categorical analyses of the FGCRS, effect sizes were small but consistent and statistically significant,” they added. “Results stratified by APOE e4 status suggest that individuals without a strong genetic predisposition to Alzheimer’s disease may be more susceptible to vascular risk factors. If confirmed, the latter finding may inform the design of future preventive studies.”

The impairments of dementia are not entirely explained by diagnoses like Alzheimer’s disease, Lewy body dementia, and the like. Individual risk factors for cardiovascular disease (and their consequences in the form of transient ischemic attack and stroke) have known associations with cognitive impairment, particularly for hypertension. Prior work with Framingham risk scores in this setting have suggested that the score might have predictive value for cognitive decline.

Xu and colleagues added to this area of inquiry by analyzing data from participants in the Rush Memory and Aging Project, begun in 1997 with 2,155 participants who were followed up annually until 2019. Researchers included 1,588 patients free of dementia at baseline (average age about 80; 76% women). MRI data was available for 328 participants.

The group established FGCRS risk tertiles as low (4 to 13), medium (14 to 16), and high (17 to 28), which accounted for 28.6%, 29.9%, and 41.5% of the study population, respectively. Mean baseline FGCRS was 15.6 and mean baseline Mini-Mental State Examination (used for descriptive purposes, but not in the analysis) was about 28. Annual assessment included evaluations of:

  • Episodic memory: Word List Memory, Word List Recall, Word List Recognition, and immediate and delayed recall of the East Boston Story and of Story A from Logical Memory of the Wechsler Memory Scale–Revised.
  • Semantic memory: Boston Naming Test, Verbal Fluency, and the National Adult Reading Test.
  • Working memory: Digit Span Forward and Digit Span Backward from the Wechsler Memory Scale–Revised, and Digit Ordering.
  • Perceptual speed: the oral version of the Symbol Digit Modalities Test, Number Comparison, and 2 indices from a modified Stroop Neuropsychological Screening Test.
  • Visuospatial ability: a 15-item form of the Judgment of Line Orientation and a 16-item form of the Standard Progressive Matrices.

These were combined into a global composite score, with higher scores indicating better function.

In addition to their association with FGCRS scores, Xu and colleagues found that episodic memory (beta 0.080) and working memory (beta 0.054) were related to hippocampal volume, and perceptual speed was associated with WMH (beta −0.026).

“Cognitive performance in different domains may indicate specific structural brain changes,” the authors observed. “Episodic memory and working memory decline may reflect hippocampal atrophy. Poor performance in processing speed was linked to white matter lesions.”

“Rigorous randomized studies of interventions to prevent dementia through treatment of individual cardiovascular risk factors are urgently needed,” the editorialists wrote. “Until then, the results of this study suggest a useful tool for assessing dementia risk and support recommendations to aggressively manage cardiovascular risk factors in midlife, such as using the American Heart Association/American Stroke Association Life’s Simple 7 paradigm.”

Results have limited generalizability beyond white women, who made up most of the study population. Also, the summed risk score precludes analysis of which risk factors contributed much or little to the results.

  1. Cardiovascular risk scores were associated with cognitive decline; compared with the lowest tertile of cardiovascular risk, the highest tertile had faster declines in global cognition, episodic and working memory, and perceptual speed.

  2. The highest cardiovascular risk tertile was also associated with smaller volumes of the hippocampus, gray matter, and total brain, and with greater volume of white matter hyperintensities.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This project is part of CoSTREAM and received funding from the European Union’s Horizon 2020 research and innovation program.

Xu has received grants from the Swedish Research Council, the National Natural Science Foundation of China (no. 81771519), Demensfonden, the Konung Gustaf V:s och Drottning Victorias Frimurare Foundation, and Alzheimerfonden.

Iadecola is a member of the Scientific Advisory Board for Broadview Ventures. Parikh reported no relationships relevant to the contents of this paper.

Cat ID: 130

Topic ID: 82,130,730,364,914,130,192,925