European Journal of Cardiovascular Medicine

Heart rate variability (HRV), defined as the fluctuation in the time intervals between successive heartbeats, serves as a sensitive and non-invasive index of autonomic nervous system (ANS) regulation, particularly reflecting cardiovascular autonomic function and vagal tone [1]. The Central Autonomic Network (CAN), comprising interconnected cortical and subcortical brain structures, plays a pivotal role in modulating cardiac vagal activity (CVA), integrating cognitive, affective, and physiological responses [2]. Among females, the hormonal fluctuations across the menstrual cycle exert a notable influence on the CAN, leading to dynamic changes in CVA to maintain physiological homeostasis [3].

Sex hormones such as estradiol (E2) and progesterone (P4) have been shown to impact a wide spectrum of brain functions, including emotional regulation and cognitive performance. These effects are primarily mediated through high concentrations of estrogen and progesterone receptors in brain regions like the hypothalamus, limbic system, and prefrontal cortex [4–7]. Consequently, the menstrual cycle introduces periodic neuroendocrine shifts that may influence both psychological states and cognitive processes, particularly those reliant on attention, memory, and executive functioning.

Emerging evidence highlights a link between menstrual cycle-related variations in CVA and fluctuations in psychological and cognitive domains in women [8]. For instance, changes in HRV have been associated with alterations in emotional processing and cognitive control, suggesting that autonomic flexibility may underpin cognitive adaptability. Furthermore, mood disturbances such as anxiety and depression, often modulated by hormonal states, may interact with HRV patterns to further influence cognitive outcomes.[9-12]

Despite growing interest, the differential effects of HRV and psychological profiles on specific cognitive domains remain inadequately understood, especially in the context of naturally cycling females. This gap warrants comprehensive investigation into how autonomic and psychological dynamics jointly shape cognitive performance across the female lifespan.

The present study, therefore, aims to assess the differential impact of HRV parameters and psychological profiles on various cognitive domains—including verbal, visual, working, and executive memory—in a cohort of community-dwelling females aged 18 to 60 years. By elucidating these relationships, the study seeks to contribute to a more nuanced understanding of sex-specific neurovisceral integration, with potential implications for cognitive health and psychological well-being in women.

Study Design and Setting

This cross-sectional observational study was conducted over a period of 18 months in the Department of Physiology to investigate the differential effects of heart rate variability (HRV) and psychological profile on cognitive domains in females. The study was carried out in a community setting and included community-dwelling women from diverse age groups.

Participants
The study included 200 female participants between 18 and 60 years of age. All participants had completed at least 12 years of formal education to ensure adequate cognitive proficiency for valid neuropsychological assessment.

Inclusion Criteria

Female individuals aged 18 to 60 years who had received a minimum of 12 years of formal education were included in the study.

Exclusion Criteria

Participants were excluded if they met any of the following criteria:

1. History of menstrual irregularities or abnormalities
2. Diagnosis of dementia, stroke, or other neurodegenerative disorders
3. History of major psychiatric disorders such as psychosis, major depressive disorder, or anxiety disorder
4. Severe visual or auditory impairment
5. Diagnosed chronic systemic illnesses including diabetes mellitus, hypertension, chronic kidney disease, or neurological disease
6. History of cardiovascular disease or use of cardioactive medications
7. Use of psychotropic medications known to affect HRV or cognitive function
8. Known cases of Hepatitis B, Hepatitis C, or HIV infection

Heart Rate Variability Assessment

HRV was assessed using the AD Instruments PowerLab system. Measurements were taken in a quiet, controlled environment with participants in a supine position following a rest period of at least 10 minutes. HRV parameters recorded included total power (TP: 0–1.0 Hz), low frequency (LF: 0.04–0.15 Hz), high frequency (HF: 0.15–0.80 Hz), and the LF/HF ratio as an indicator of autonomic balance. All recordings were performed during spontaneous breathing to minimize confounding influences.

Neuropsychological Assessment

Cognitive functions were evaluated using a standardized battery of neuropsychological tests. Verbal memory was assessed using the Rey Auditory Verbal Learning Test (RAVLT). Visual memory was evaluated using Rey’s Complex Figure Test. Working memory was measured through digit span and spatial span tasks (forward and backward), while executive function was assessed using the Color-Word Stroop Test. All tests were administered by trained personnel under standardized conditions.

Psychological Assessment

The psychological profile of each participant was assessed using the Hamilton Anxiety Rating Scale (HAM-A) and the Beck Depression Inventory-II (BDI-II). These assessments were conducted through structured interviews to ensure reliability and consistency in scoring.

Ethical Considerations

Ethical approval for the study was obtained from the Institutional Ethics Committee prior to data collection. Written informed consent was obtained from all participants after providing detailed information about the study’s purpose, procedures, and confidentiality protocols.

Statistical Analysis

Data were expressed as mean ± standard deviation (SD). Group comparisons were conducted using two-tailed Student’s t-tests for normally distributed variables. Pearson’s correlation and multiple regression analysis were applied to explore associations between HRV indices, psychological variables, and cognitive performance. A p-value of less than 0.05 was considered statistically significant. Data analysis was carried out using appropriate statistical software such as SPSS or R.

The study enrolled 200 community-dwelling females aged 18–60 years (mean age: 38.4 ± 12.3 years) to evaluate the differential effects of heart rate variability (HRV) and psychological profiles on cognitive domains. Data were analyzed to explore associations between HRV parameters, psychological variables (anxiety and depression scores), and cognitive performance across verbal, visual, working, and executive memory domains.

Table 1: Demographic and Baseline Characteristics

Table 2 summarizes the heart rate variability (HRV) parameters of the participants. The mean total power (TP) was 2450.6 ms² (±892.4), indicating the overall autonomic activity. The low-frequency (LF) power averaged 820.4 ms² (±312.7), while the high-frequency (HF) power, reflecting parasympathetic activity, averaged 1050.8 ms² (±456.2). The LF/HF ratio, an index of sympathovagal balance, was 0.78 (±0.29), suggesting a predominance of vagal tone in the sample.

Table 2: Heart Rate Variability (HRV) Parameters

Table 3 provides the psychological profile of the participants, as measured by the Hamilton Anxiety Rating Scale (HAM-A) and the Beck Depression Inventory-II (BDI-II). The mean HAM-A score was 8.4 (±4.7), with a range from 0 to 22, indicating generally mild levels of anxiety within the sample. The mean BDI-II score was 7.9 (±5.2), ranging from 0 to 24, suggesting minimal to mild depressive symptoms across participants.

Table 3: Psychological Profile Assessment

Table 4 illustrates the cognitive performance across different domains. In the domain of verbal memory, as measured by the Rey Auditory Verbal Learning Test (RAVLT), participants had a mean total recall score of 48.6 (±7.8). Visual memory, assessed through the Rey’s Complex Figure Test, yielded a mean recall score of 22.4 (±5.6). Working memory, evaluated via the combined forward and backward digit span tasks, had a mean score of 14.8 (±3.2). Executive function, measured using the Stroop Test interference score, averaged 45.2 (±9.4), indicating the participants' ability to manage cognitive interference.

Table 4: Cognitive Performance Across Domains

Table 5 displays the correlation analysis between HRV indices, psychological variables, and cognitive domain scores. A significant positive correlation was observed between HF power and verbal memory (r = 0.32, p = 0.001), as well as with working memory (r = 0.28, p = 0.004). Conversely, the LF/HF ratio showed a negative correlation with executive function (r = -0.25, p = 0.008). Psychological variables also demonstrated inverse relationships with cognitive outcomes: HAM-A scores negatively correlated with verbal memory (r = -0.30, p = 0.002) and executive function (r = -0.29, p = 0.003), while BDI-II scores negatively correlated with visual memory (r = -0.27, p = 0.006).

Table 5: Correlation Analysis Between HRV, Psychological Variables, and Cognitive Domains

Table 6 presents the results of multiple regression analyses predicting performance in various cognitive domains. For verbal memory, HF power emerged as a significant positive predictor (β = 0.28, p = 0.002), while higher HAM-A scores predicted lower performance (β = -0.22, p = 0.008), with the overall model explaining 24% of the variance. In the visual memory domain, BDI-II scores were negatively associated with performance (β = -0.25, p = 0.005), accounting for 19% of the variance. Working memory was positively predicted by HF power (β = 0.24, p = 0.007), with an R² of 0.21. For executive function, both the LF/HF ratio (β = -0.27, p = 0.004) and HAM-A scores (β = -0.20, p = 0.012) were significant negative predictors, with the model explaining 23% of the variance in performance.

Table 6: Multiple Regression Analysis for Cognitive Domains

The present study aimed to assess the differential effect of heart rate variability (HRV) and psychological profile on cognitive performance across multiple domains—verbal, visual, working, and executive memory—in community-dwelling females. The results offer meaningful insights into the neurovisceral interactions that underpin cognitive functioning in women and underscore the complex interplay between autonomic regulation, psychological state, and cognition.

A key finding of this study was the significant positive association between high-frequency (HF) power, an index of parasympathetic (vagal) activity, and performance in both verbal and working memory tasks. This aligns with the neurovisceral integration model proposed by Thayer and Lane [2], which posits that increased cardiac vagal control, as reflected by HF power, supports better functioning of the prefrontal cortex and other regions involved in attention, memory, and executive regulation. Furthermore, Schmalenberger et al. [8] emphasized cyclical changes in cardiac vagal activity across the menstrual cycle and their potential influence on cognitive-emotional processes, a phenomenon that may explain individual variability within the current sample. The positive predictive value of HF power for working memory, as seen in our multiple regression analysis, reinforces findings by Mahinrad et al. [12], who reported that even short-duration HRV measures correlate with cognitive ability in older adults.

In contrast, a higher LF/HF ratio—a marker of sympathovagal imbalance—was found to be negatively associated with executive function. This result is consistent with findings from the CARDIA study by Zeki Al Hazzouri et al. [3], which linked reduced autonomic flexibility to poorer cognitive performance in middle-aged adults. The inverse association observed in our study suggests that a heightened sympathetic state or diminished vagal tone may impair cognitive control mechanisms, potentially via reduced top-down regulation from the prefrontal cortex. Such mechanisms are particularly relevant to executive functioning, which requires cognitive flexibility, inhibition, and working memory—domains sensitive to stress and autonomic dysregulation. [13,14]

Our findings also demonstrated a notable influence of psychological variables on cognitive outcomes. Anxiety, as measured by the Hamilton Anxiety Rating Scale (HAM-A), was significantly and negatively associated with verbal memory and executive functioning. This echoes the findings of Sundström-Poromaa and Gingnell [4], who highlighted the adverse effects of hormonal fluctuations on emotional regulation and cognition, particularly during phases of increased anxiety and emotional instability across the menstrual cycle. Similarly, higher depression scores on the Beck Depression Inventory-II (BDI-II) predicted poorer visual memory performance, supporting earlier work by Segal et al. [14] that showed depressive symptoms significantly impair encoding and recall, especially in visually loaded tasks.

The impact of psychological state on cognitive domains in the context of fluctuating autonomic control further supports the notion of a bidirectional relationship between mood and HRV. As proposed in earlier studies [5–7], estradiol and progesterone interact with neurotransmitter systems such as dopamine and serotonin, influencing both mood and cognition. Given the presence of estrogen and progesterone receptors in brain regions like the prefrontal cortex and hippocampus [5,6], hormonal modulation likely contributes to both autonomic reactivity and cognitive variability, particularly across menstrual phases. Though the current study did not stratify cognitive performance by menstrual cycle phase, the representation of both follicular and luteal phases (46% and 54%, respectively) offers ecological validity to the sample.

In addition, the relatively low levels of anxiety and depression observed in our sample suggest that even subclinical psychological symptoms can meaningfully affect cognitive function, particularly in the presence of altered autonomic tone. This observation aligns with the findings of Mahinrad et al. [12], who noted significant associations between mild psychological distress and decreased HRV, subsequently linked to cognitive decline.

The overall explanatory power of the regression models (R² ranging from 0.19 to 0.24) indicates that both HRV and psychological factors account for a moderate but meaningful proportion of the variance in cognitive scores. While this suggests other biological and environmental variables may contribute to cognitive performance, it confirms the value of assessing both physiological and psychological components when evaluating female cognitive health.

Despite the strengths of this study—including a well-characterized sample, comprehensive cognitive testing, and concurrent HRV and psychological assessment—certain limitations should be acknowledged. The cross-sectional design limits causal inference, and menstrual phase was not controlled as a variable in cognitive analysis, although participants were fairly distributed across phases. Additionally, hormonal levels (e.g., estradiol, progesterone) were not directly measured, which could have provided more precise correlations with HRV and cognitive changes. Future longitudinal and interventional studies incorporating hormonal assays and phase-specific tracking would be valuable in deepening our understanding of the observed relationships.

In conclusion, the findings of this study highlight the significant and differential impact of HRV parameters and psychological state on cognitive performance in females. Specifically, enhanced parasympathetic activity and lower anxiety and depression levels were associated with better performance across cognitive domains. These results contribute to the growing body of evidence on sex-specific neurovisceral integration and underscore the importance of considering both autonomic and psychological health in understanding and promoting cognitive well-being in women.

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