Inflammation-Insulin Resistance Marker Linked to Cognitive-Motor Syndrome in Older Adults

A simple calculation combining two routine blood tests—one for inflammation and one for insulin resistance—may flag older adults at risk of a little-known but increasingly worrying condition that couples cognitive decline with slow walking speed. That is the central claim of a new cross-sectional study published in BMC Geriatrics, which found that Chinese older adults with higher scores on the C-reactive protein-triglyceride glucose index, known as CTI, were significantly more likely to have motoric cognitive risk syndrome, or MCR. The findings add weight to the idea that chronic low-grade inflammation and metabolic dysfunction do not merely coexist in aging bodies but may jointly drive the earliest, most treatable stages of cognitive deterioration.

Motoric cognitive risk syndrome is a pre-dementia condition defined by two features: subjective cognitive complaints—memory lapses or attention problems that the person notices but that do not yet meet criteria for dementia—and objectively slow gait speed measured on a walking test. First proposed just over a decade ago, MCR has attracted attention precisely because it sits in the window before overt dementia, when interventions such as exercise, metabolic control, and vascular risk management still have a chance to alter the trajectory. Estimates suggest that roughly one in ten community-dwelling older adults worldwide may meet the criteria, making it one of the most common prodromal dementia syndromes in the population.

The CTI, meanwhile, is a composite biomarker that merges two distinct strands of aging biology into a single number. It is calculated by taking the natural logarithm of C-reactive protein multiplied by triglycerides, divided by the product of total cholesterol and high-density lipoprotein cholesterol, and then adding that value to the natural logarithm of fasting glucose multiplied by fasting insulin divided by 22.5—the core of the well-established triglyceride-glucose, or TyG, index of insulin resistance. In plain terms, the first component captures systemic inflammation via C-reactive protein, an acute-phase protein produced by the liver, while the second component captures how effectively the body’s cells respond to insulin, a metabolic parameter long implicated in dementia risk. Because both blood panels are cheap, widely available, and already collected in routine clinical work, CTI offers a practical way to quantify the combined inflammatory-metabolic burden without any specialized equipment.

The research team, led by Liping Chen and Dingchang Wu of Longyan First Affiliated Hospital of Fujian Medical University, drew their data from the baseline period of the China Health and Retirement Longitudinal Study, or CHARLS, a nationally representative survey of middle-aged and older Chinese adults. After applying their inclusion criteria, the analysis settled on 4,002 participants aged 60 and above. Of these, 503 individuals—12.6 percent of the sample—met the diagnostic criteria for MCR, a prevalence consistent with international estimates. Participants with the syndrome had a mean CTI score of 4.87, and the researchers set out to determine whether that number was meaningfully elevated compared with their cognitively and physically intact peers.

Because CTI is a continuous measure, the investigators divided participants into quartiles, from the lowest inflammatory-metabolic burden to the highest. In the crude comparison, the highest quartile carried substantially more MCR cases than the lowest. But the crucial test came after statistical adjustment. Using multivariate logistic regression, the team controlled for a comprehensive battery of covariates—demographic factors such as age and sex, socioeconomic variables, lifestyle behaviors including smoking and drinking, and clinical parameters such as hypertension, diabetes, dyslipidemia, and body mass index. Even after all of these adjustments, the association held: participants in the highest CTI quartile had 1.449 times the odds of having MCR compared with those in the lowest quartile, with a 95 percent confidence interval of 1.095 to 1.921. An odds ratio above 1 with a confidence interval that does not cross 1 is the standard statistical signal that the elevated risk is unlikely to be a chance finding.

The team also ran a weighted sensitivity analysis, re-running the model with survey weights to account for CHARLS’s complex sampling design and ensure the result reflected the broader Chinese population rather than just the analytic sample. The weighted odds ratio came out at 1.490, with a 95 percent confidence interval of 1.076 to 2.064—essentially the same signal, slightly stronger, and still statistically robust. Subgroup analyses, which stratified the sample by variables such as sex, age band, and comorbidity status, showed the association persisted across these strata, suggesting the finding is not confined to a particular demographic pocket within the older population.

Perhaps the most technically interesting result, however, came from the restricted cubic spline analysis, a modeling technique that allows the relationship between a continuous exposure and an outcome to bend rather than forcing it into a straight line. The spline analysis revealed a nonlinear, N-shaped relationship between CTI and MCR, with an overall P value below 0.001 and a P value for nonlinearity of 0.012. In practical terms, this means the risk of MCR does not simply climb in lockstep with every incremental rise in the index. Instead, the curve rises steeply at lower CTI values, may plateau or dip in the middle range, and then rises again at higher values—an N-shaped pattern that hints the inflammatory-metabolic burden may interact with other biological pathways in a more complex fashion than a simple dose-response model would suggest.

What might explain the biological plausibility of this link? Chronic low-grade inflammation is increasingly recognized as a contributor to neurodegeneration. C-reactive protein itself does not cross the blood-brain barrier in meaningful quantities, but its elevation signals that inflammatory cytokines are circulating throughout the body, and these signaling molecules can activate microglia—the brain’s resident immune cells—promoting a state of neuroinflammation that damages synapses and accelerates neuronal loss. Insulin resistance, for its part, impairs the brain’s ability to take up glucose, its primary fuel, and interferes with insulin signaling pathways in the hippocampus that are critical for memory consolidation. Slow gait speed, the motoric component of MCR, is itself linked to vascular damage, sarcopenia, and metabolic dysfunction, so a marker that captures both inflammation and insulin resistance may be flagging the shared biological substrate that underlies both the cognitive and the motoric features of the syndrome.

The study’s cross-sectional design, however, imposes important limits on interpretation. Because exposure and outcome were measured at the same point in time, the analysis cannot establish whether elevated CTI precedes the onset of MCR or whether the syndrome itself—through reduced physical activity, altered metabolism, or incipient disease processes—drives the marker upward. Reverse causation remains a genuine possibility, and the authors are careful to frame their findings as an association rather than a causal claim. Longitudinal follow-up of the CHARLS cohort, which continues to collect wave after wave of data on the same participants, would be the natural next step to disentangle the direction of the relationship and determine whether baseline CTI predicts incident MCR in previously unaffected individuals.

Still, the practical implications are hard to ignore. CTI requires nothing beyond a standard lipid panel, fasting glucose, fasting insulin, and C-reactive protein—tests that are already ordered routinely in primary care and hospital settings across China and much of the world. If future longitudinal studies confirm that the index predicts MCR and, downstream, dementia, clinicians could conceivably incorporate it into risk stratification tools that identify older adults who would benefit most from aggressive metabolic control, anti-inflammatory lifestyle interventions, or structured exercise programs targeting gait speed. With global aging accelerating and dementia cases projected to rise sharply in the coming decades, a cheap, reproducible biomarker that couples two well-understood biological pathways into a single actionable number may prove to be exactly the kind of early-warning signal the field has been searching for.

Subject of Research: Association of the C-reactive protein-triglyceride glucose index with motoric cognitive risk syndrome in Chinese older adults: a cross-sectional study

Article Title: Association of the C-reactive protein-triglyceride glucose index with motoric cognitive risk syndrome in Chinese older adults: a cross-sectional study

Article References: Chen, L., Xiao, T., Ruan, Y., Zhang, W., & Wu, D. (2026). Association of the C-reactive protein-triglyceride glucose index with motoric cognitive risk syndrome in Chinese older adults: a cross-sectional study. BMC Geriatrics. https://doi.org/10.1186/s12877-026-08486-4

Image Credits: AI Generated

DOI: 10.1186/s12877-026-08486-4

Keywords: Association, C-reactive, protein-triglyceride, glucose, index, motoric, cognitive, risk, syndrome, Chinese, older, adults