Clock Drawing Test Detects Silent Brain Damage in Hypertensive Patients

According to an observational, cross-sectional investigation published in the journal Artery Research, subclinical brain damage is significantly more prevalent among individuals with essential hypertension than preclinical damage to either the heart or the kidneys. By employing the clock-drawing test as an accessible cognitive screening tool, the research team found that 38 percent of evaluated patients demonstrated early, silent brain impairment. Most critically, the assessment uncovered that nearly one-third of hypertensive individuals who exhibited no preclinical heart or kidney complications had already sustained measurable cerebral injury, exposing a substantial diagnostic gap in contemporary cardiovascular risk stratification models that typically evaluate only cardiorenal biomarkers.

Target organ damage has long served as a cornerstone concept established by joint hypertension committees to recognize subclinical organ injury early, preserve physiological function, prevent catastrophic complications, and refine risk assessments. Prior neuroimaging research cited by the authors, including work by Henskens and colleagues, confirmed that 35 percent of hypertensive patients without cardiorenal damage already harbor cerebral white matter lesions on magnetic resonance imaging. Nevertheless, the substantial financial expense and practical logistical barriers of universal neuroimaging preclude magnetic resonance screening across general hypertensive populations, creating an urgent need for surrogate clinical markers.

To explore an accessible clinical alternative, researchers organized across the Heart-Brain Federal Network in Argentina, collaborating across multiple clinical centers in South America, evaluated whether functional cognitive testing could effectively identify subclinical vascular brain injury. Because cerebral small vessel disease resulting from persistent hypertension directly compromises microvascular perfusion and connectivity, the researchers conceptualized subtle cognitive impairment as an actionable clinical surrogate for underlying vascular brain damage. The study aimed to measure the specific prevalence rates of cerebral, cardiac, and renal target organ damage within a real-world clinical cohort, assessing whether the noninvasive clock-drawing test could successfully serve as a dependable, routine screening instrument across regular consulting room environments.

The multicenter and multinational study enrolled 487 adult outpatients diagnosed with essential hypertension who presented between August 2019 and February 2020 at five specialized hypertension units, consisting of four centers in Argentina—located in Buenos Aires, Corrientes, Tucumán, and Santa Fe—and one center in Montevideo, Uruguay. The cohort was restricted to individuals aged 21 years or older who met the diagnostic criteria for essential hypertension outlined in Argentine and European management guidelines, defined as exhibiting a systolic blood pressure of at least 140 mm Hg, a diastolic blood pressure of at least 90 mm Hg, or currently receiving antihypertensive medical therapy. Of the enrolled cohort, 441 participants successfully completed every required clinical, biochemical, and cognitive measurement protocol and were incorporated into the final analytical sample.

To isolate hypertension-mediated damage from unrelated etiologies, the investigative team applied strict exclusionary criteria. Individuals were excluded if they presented with established neurological conditions such as prior stroke or advanced Parkinson’s disease, severe psychiatric disorders including schizophrenia, major depressive disorder, bipolar disorder, or dementia defined by standard diagnostic manuals, or if they were undergoing treatment with cholinesterase inhibitors, glutamatergic agents, or antipsychotic drugs, although the therapeutic use of benzodiazepines was permitted.

Target organ damage was systematically quantified across cardiac, renal, and cerebral domains using standardized diagnostic criteria. Renal function and preclinical damage were evaluated through serum creatinine concentration and estimated glomerular filtration rate calculated via the Cockcroft-Gault equation, defining impairment as a serum creatinine level exceeding 1.2 mg/dl, an estimated filtration rate below 60 ml/min, or both. Preclinical cardiac damage was determined via two-dimensional M-mode and Doppler echocardiography, measuring left ventricular mass through Devereux’s formula and indexing the value to body surface area; elevated left ventricular mass index values of at least 95 grams per square meter for women and 115 grams per square meter for men established hypertensive cardiac involvement.

Cerebral target organ damage was assessed using a standardized seven-point clock-drawing test administered and scored by trained cardiologists during routine clinical consultations, with scoring verified through an independent, double-blind evaluation by a second trained cardiologist. The examination provides patients with a sheet of paper containing a pre-drawn circle measuring ten centimeters in diameter, which enhances test sensitivity and prevents confounding distortions such as oval drawing. Patients are instructed first to imagine the circle as a clock face and draw all numbers in their correct order and location, which contributes up to three points toward evaluating executive function. Immediately following number placement, patients are instructed to draw the clock hands pointing specifically to twenty past four, contributing up to four points to assess semantic memory, alongside broader cognitive elements including verbal comprehension, motor planning, graphomotor execution, planning, and visuospatial skills. A composite score of five or fewer points was defined as cognitive impairment indicative of silent brain damage.

Among the 441 patients analyzed, who presented with a mean age of 63.2 years and included 53.2 percent women, target organ damage was remarkably prevalent, with 60.5 percent of all participants exhibiting impairment across at least one organ system. Preclinical cardiac damage was documented in 32.8 percent of participants, while renal impairment appeared in 20.4 percent of the sample. In contrast, silent brain damage identified via an abnormal clock-drawing test was observed in 38.0 percent of the total patient population. When examining subgroups categorized by cardiorenal status, abnormal clock drawings were observed in 47.2 percent of patients who exhibited concurrent cardiac, renal, or combined damage, and in 30.7 percent of hypertensive participants who showed no detectable cardiac or renal impairment whatsoever.

Analysis of cognitive subcomponents revealed that among the 168 hypertensive patients demonstrating an abnormal clock-drawing performance, 75.5 percent exhibited combined deficits spanning both executive function and semantic memory domains. These behavioral patterns align directly with the neuropathology of chronic hypertension, which induces cerebral small vessel disease characterized by subcortical ischemic demyelination that disrupts connectivity across the frontal-subcortical and temporal-subcortical neural circuits.

The study also documented pronounced demographic disparities in cognitive outcomes. Patients with lower educational attainment experienced substantially higher rates of test failure, with abnormal clock scores appearing in 68.3 percent of individuals with seven or fewer years of schooling, 42.1 percent of those with eight to twelve years, and 27.5 percent of participants possessing twelve or more years of education. Female participants also recorded lower average test scores than male participants, registering a mean score of 3.5 points compared to 5.5 points among men, an outcome the investigators attributed to an older average age among enrolled female subjects. Interestingly, target organ damage was not correlated with self-reported hypertension duration, which the authors noted likely reflects the inherent unreliability and questionable validity of subjective, participant-reported recall regarding when high blood pressure originally developed.

The authors stressed that the cross-sectional nature of the study precludes drawing conclusions regarding long-term clinical progression or predicting future cerebrovascular events. Nonetheless, the multicenter design spanning five hospital units in two South American countries provides robust regional evidence regarding the clinical utility of cognitive screening in primary hypertension management. Citing the Lancet Commission report, which established hypertension as the leading modifiable vascular risk factor among fourteen risks accounting for 45 percent of worldwide dementias, the researchers concluded that incorporating the simple, inexpensive clock-drawing test into routine clinical visits provides an indispensable opportunity to identify silent cerebral microvascular damage, correct cardiovascular risk underestimation, and implement timely interventions before irreversible cognitive decline develops.

Subject of Research: Screening for subclinical hypertension-mediated brain damage using the clock-drawing test

Article Title: Early Detection of the Hypertension-Mediated Brain Damage Using the Clock-Drawing Test

Article References: Vicario, A., De Cerchio, A. E., Patrón, F. R., Cesario, D., Spósito, P., Cerezo, G. H., & Researchers of the Heart-Brain Federal Network in Argentina (2026). Early Detection of the Hypertension-Mediated Brain Damage Using the Clock-Drawing Test. Artery Research, 32(1), Article 17. https://doi.org/10.1007/s44200-026-00114-1

Image Credits: AI Generated

DOI: 10.1007/s44200-026-00114-1

Keywords: hypertension, clock-drawing test, target organ damage, cognitive impairment, vascular brain damage, cardiovascular risk, cerebral small vessel disease, artery research, Early, Detection, Hypertension-Mediated, Brain