Despite the enormous efforts of healthcare professionals, cardiovascular diseases (CVDs) and their complications have become a global burden on society and the economy due to the aging population (1, 2). Mild cognitive impairment is a transitional state between normal cognitive aging and dementia when activities of daily living are not limited. A considerable amount of literature demonstrated that CVDs and dementia share risk factors. According to the latest report of the 2020 Lancet Commission on dementia prevention, intervention and care, 12 potential risk factors may be responsible for the deterioration of cognitive function. Half represent classic cardiovascular risk factors (CVRFs): arterial hypertension, diabetes mellitus, smoking, high alcohol intake, obesity, and sedentarism (3). In Romania, dementia accounts for 1.43% of the population and is expected to rise to 2.56% by 2050 (4). This data refers to diagnosed dementia cases when the disease is usually advanced. Currently, there is no data about the prevalence of mild cognitive impairment in Romania.

Cognitive dysfunction (CD) and dementia mainly occur in the older adult population (4). However, in the Young Finns Study, CVRFs in childhood and adolescence were associated with lower cognitive function in midlife (5). Researchers along the heart-brain axis have studied the relationship between CD and cardiovascular pathologies (6). According to our knowledge, myocardial infarction, heart failure (HF) and atrial fibrillation (AF) are the most investigated pathologies lately. Ischemic heart disease, such as myocardial infarction or previous surgical revascularization for coronary heart disease and even high coronary calcium score were associated with an increased risk of CD development (7–9). AF is the most common arrhythmia with an increased risk for thromboembolism, often leading to ischemic stroke (10). Stroke plays an undisputed role in the deterioration of cognitive function (10). However, AF increases the risk of CD independently of stroke in older adults (11). Comorbid depressive symptoms are common in patients with CVDs and not only did they increase the short-and long-term risk for adverse cardiovascular events (12) but they also accelerated cognitive decline in a one-year follow-up (13).

Heart and brain health have much in common and this explains why this topic has received considerable interest nowadays. We hypothesized that individuals with different CVDs have worse cognitive performance and the impact on CD severity differs depending on the type of CVD. This study aimed to examine the prevalence of CD in the most common CVDs, such as atherosclerotic diseases, HF, AF and stroke. Furthermore, our objective was to evaluate the contribution and scale of the impact of demographic data, CVDs and two of the commonly co-occurring health conditions with CVDs, renal dysfunction (RD) and depression on cognitive deterioration.

According to the dementia forecast, the number of people living with CD is increasing due to the higher life expectancy and age is the main risk factor (2, 15). A considerable number of patients are not diagnosed (16). Since middle-aged and older adult patients commonly have multiple comorbidities, we thought it would be appropriate to investigate this patient profile. This study examined the prevalence of cognitive impairment in patients with CVDs in a Romanian sample. We found that cognitive impairment is high among patients with CVDs and the most common form is mild cognitive impairment. We investigated the relationship between cognitive impairment and gender, age, educational level, cardiovascular risk factors, the most common cardiovascular pathologies, and frequently associated conditions with CVDs, such as RD and depression. A significant association was found between gender, age group, level of education, smoking, AF, stroke, RD, depression and the severity of CD (Figure 2).

Researchers of the SHARE Database depicted a recent and authentic image of Europe from the CD point of view. Data was obtained from 16 European countries enrolling more than thirty thousand subjects aged 50 years or over. They found a decline in verbal fluency, perceived memory, and numeracy between 20.75 and 28.02% in the domains of the Mini-Mental State Examination test. In Hungary, another Eastern European country, a higher prevalence of impairment of perceived memory and verbal fluency (32.7 and 39.0%) was observed compared to global results (17). In the Romanian population, the only existing data is about dementia, whose prevalence was 279,607 individuals, representing 1.43% of the total population, according to the 2019 Dementia in Europe Yearbook (4). In our sample, the prevalence of CD was higher. We assessed CD in patients with established cardiovascular pathologies, contrary to Lourenco et al., where data referred to the general population (17). On the other hand, in a cross-sectional study conducted among community residents over 65 years, the overall incidence of cognitive impairment was 54.9% (18). These findings are closer to our results, not to mention that our research included patients with CVDs. Overall, the results highlighted the different prevalence of cognitive status between countries and may motivate other countries to obtain population data.

The present study’s findings are consistent with the main and established risk factor for cognitive decline (19). Older age (≥70 years) had a negative impact on cognition, both in mild and advanced CD. In addition, the female gender was a risk factor for advanced CD, which has already been confirmed in prior studies (20, 21). Furthermore, in line with other studies, we found that higher education is a protective factor for cognitive function. Longitudinal studies suggested that nine and 10 classes could be determinative in preserving cognitive abilities (22, 23). Our results confirmed that 9 years of education could be the threshold.

Despite expectations based on previous research (6, 17, 24), our study did not demonstrate a significant association between CVRFs and cognitive impairment, except for smoking. Unlike some previous reports, our correctly applied statistically grounded result on smoking in the studied cohort of patients indicated a different finding. In the present paper, smoking appeared to be a protective factor for mild and advanced CD. Smoking cessation is one of the potentially modifiable risk factors to prevent all types of dementia (3). Moreover, a meta-analysis revealed that active and former smokers had a significantly increased risk for all-cause dementia, Alzheimer’s disease, and vascular dementia compared to non-smokers. This association was weaker in former smokers than in current smokers (25). This may further favor smoking cessation. However, a limited body of evidence showed a positive effect of smoking on various cognitive domains, such as attention, short-, and long-term memory (26). It was suggested that the nicotine compound of the cigarette could be responsible for this improvement (27). Moreover, the administration of lower-dose nicotine gum in young non-smokers showed improvement in cognitive performance (28). Taking into consideration the massive scientific data about the harmful effects of smoking (29), our result that smoking might have a positive effect on cognition in this patient sample highlights the gaps in evidence and implies future investigation of the research team. From blood-derived CVRFs, such as glucose, lipid profile, homocysteine, high sensitivity C-reactive protein, only increased high-density lipoprotein cholesterol level was associated with better cognitive function after 2 years in individuals with normal baseline cognitive function (30). Similar results were found in 1324 community residents, where the incidence of CD was significantly higher in individuals with arterial hypertension and low level of low-density lipoprotein cholesterol, but not with other CVFRs (18). In addition, heart diseases and risk factors sometimes overlap. Grouping cardiovascular pathologies in cognitive studies is more common in the literature than assessing a single disease. In a study with self-reported CVDs such as “heart attack, coronary heart disease, angina, congestive heart failure or other heart pathologies” there was no increase in the risk of CD compared to patients without CVDs for 8 years of follow-up (31). A Mexican study analyzing 1807 subjects concluded that CVDs in mid-life, but not late-life disease, increased the likelihood of mild cognitive impairment by 1.7 times. In this study, cumulative CVDs, such as arterial hypertension, diabetes mellitus, heart disease, and stroke, were considered. Further evaluation of one single disease from those mentioned above demonstrated that arterial hypertension and diabetes mellitus in mid-life and late-life heart disease increased the risk of mild cognitive impairment (32). It must be mentioned that this longitudinal study also applied self-reported CVDs. The main practical problem that concerns us is implementing these results in a middle-aged or older adult patient with more than one pathology. These results may suggest that the relationship between CVDs and cognitive decline should be assessed separately for pathologies. In contrast to other colleagues, we included patients with documented pathologies, as self-reported or anamnestic health conditions may mask biases.

A large body of evidence supports that ischemic heart disease, AF, and stroke are risk factors for vascular dementia (19). Previous diagnostics of AF and ischemic stroke increased the risk for advanced cognitive decline in our study, but not for mild CD with a weak effect size. Clinical data showed that not only did AF represent a risk factor for CD (19) but a longer history of AF was suggested to lead to faster deterioration of cognitive performance (33). Advanced CD, such as dementia, may raise concerns, as deterioration of cognitive domains interferes with activities of daily living (3). Our findings suggest that AF and a history of stroke similarly impact cognitive function. Considering that some of the risk factors for CD from our results are non-modifiable, such as age, gender, and educational level, the presence of AF could be a modifiable risk factor in some instances. However, data are insufficient to support rhythm or frequency control in AF patients to prevent CD (34). Anticoagulation therapy could offer a protective effect against CD in AF patients, although further research is needed to confirm this hypothesis (34, 35). Stroke-related decline in cognitive function is an acknowledged complication of stroke (36, 37). Unfortunately, few patients can expect to recover from it (38). Even though contrary results have been reported too, in a study with 7 years of follow-up the incidence of CD in patients with and without stroke was not significantly different (39). The outcome of cognitive performance after stroke is uncertain, but cognitive reserve may represent a protective factor (40).

Insufficient data is available in the case of low cardiac output conditions (19). Approximately half of the participants had a history of heart failure, which was in accordance with other studies (41). Even though the prevalence of CD was high in HF patients in our study, no association between HF and the severity of CD was found, regardless of the HF type and level of EF. Prior research has found an increased risk for CD in patients diagnosed with HF either with reduced or preserved EF (HFrEF, HFpEF) (42) and in any reduction of LVEF (43, 44). Even the NYHA class of ≥II was associated with the decline of cognitive function in patients with HFrEF (45). Nevertheless, it is needed to mention that 77% of HF patients in the present study were documented with preserved ejection fraction, the patients were relatively well compensated and there was no need for high doses of loop diuretics and inotropic/vasopressor usage.

We found a considerable proportion of patients who had comorbid conditions such as RD and depressive symptoms. A systematic review and meta-analysis revealed that the prevalence of depression was 32% in patients with CD, with a higher proportion in clinical studies compared to community studies (46). Depressive symptoms were positively correlated with CD. RD was associated with the severity of CD and increased the risk of cognitive decline with moderate association strength. An eGFR between 30 and 59 mL/min/1.73m² increased the likelihood for mild and advanced CD, while eGFR 60–90 mL/min/1.73m² for advanced CD. In the “Reasons for Geographical and Racial Differences in Stroke” (REGARDS) study, eGFR<60 mL/min/1.73m² was associated with CD (47) and it was also demonstrated in HFrEF patients measured by the Mini Mental State Examination test (45).

Although most of the research in the field of cognitive impairment among patients with CVDs was performed on older adult individuals, midlife CVDs also hide a risk for cognitive decline in younger patients. A longitudinal study over 30 years has found that cognitive dysfunction was associated with premature CVDs (the term of premature denoted patients <60 years) and with a higher percentage of white matter hyperintensities on brain magnetic resonance images (48). These findings emphasize whether the key factor in maintaining cognitive function is the prevention of CVDs. This research question was aimed at the FINGER trial (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability). The authors revealed that intensive control and management of risk factor as well as specific recommendations and interventions related to cognitive training and healthy lifestyle, such as advice on diet, physical activity, and weight loss, contributed significantly to the reduction in cognitive decline in older patients from the general population at risk for dementia (49).

While other studies searched for an association between risk factors, diseases, and CD, we investigated whether there is a difference between these conditions and the severity of CD. Few studies assessed the strength of the association between demographic data, CVDs, and related pathologies and cognitive decline. The novelty of this study lies in more aspects. Firstly, we revealed the prevalence of CD in a high-risk sample and also found that the most common form of CD was mild CD. Secondly, we demonstrated that some of the investigated pathologies hide a greater risk for advanced CD, such as atrial fibrillation and stroke in comparison with mild CD. Furthermore, we investigated CVDs separately against global CVDs.

An obvious limitation of our study was the observational design and the absence of a control group from the general population or primary health services. Our study may overestimate the prevalence of CD in the general population since we included patients hospitalized for specific reasons, sometimes with multiple CVDs. In addition, we utilized a cognitive test that assesses various cognitive domains, but instead we focused on global cognition. Furthermore, given that we conducted a cross-sectional study, cognitive performance was measured once. All authors agree that longitudinal follow-up is needed for more robust findings and conclusions.

The findings of the present manuscript show that in patients with CVDs mild cognitive impairment was more common than advanced (moderate or severe) CD. AF and stroke were associated with the severity of cognitive decline with a weak association of strengths. Moreover, AF, stroke and female gender increased the probability of advanced CD but did not influence mild CD. The likelihood for mild and advanced CD was increased by advanced age, lower level of education, renal dysfunction, and being a non-smoker. The clinical implications of these findings remain subject to future investigations.