Effect of Comorbidities on Ten-Year Survival in Patients with Dementia

Abstract

Background:

There is a verified association between comorbidity and survival in patients with dementia.

Objective:

To describe the ten-year survival probability of patients with dementia and to identify the impact of comorbidity.

Methods:

The prognostic retrospective cohort study was conducted using data from adults with dementia who had visited the outpatient departments at Maharaj Nakorn Chiang Mai hospital between 2006 and 2012. Dementia was verified in accordance with standard practice guidelines. Secondary data detailing about patient age, gender, date of dementia diagnosis and death, types of dementia, and comorbidities at the time of dementia diagnosis was obtained from electronic medical records. The association between comorbidity, patients’ underlying disease at dementia diagnosis, and overall survival were analyzed using a multivariable Cox proportional hazard model adjusted for age, gender, types of dementia, and other comorbidities.

Results:

Of the 702 patients, 56.9% were female. Alzheimer’s disease (39.6%) was the most prevalent type of dementia. Median overall survival was 6.0 years (95% CI 5.5– 6.7). The comorbidities associated with a high risk of mortality included liver disease (aHR 2.70, 95% CI 1.46– 5.00), atrial fibrillation (aHR 2.15, 95% CI 1.29– 3.58), myocardial infarction (aHR 1.55, 95% CI 1.07– 2.26), and type 2 diabetes mellitus (aHR 1.40, 95% CI 1.13– 1.74).

Conclusion:

Overall survival rate of patients with dementia in Thailand was comparable to previous studies. Several comorbidities were associated with a ten-year survival. The prognosis of patients with dementia may be improved by appropriate care of comorbidities.

Keywords

Alzheimer’s disease comorbidity dementia survival time

INTRODUCTION

Dementia is defined by a decrease in one or more cognitive domains, including those pertaining to learning and memory, language, executive function, complex attention, perceptual-motor, and social cognition. The deficiencies would show a deterioration from the previous level of self-care capacity and be severe enough to impair everyday functioning and independence. It causes progressive deterioration in patients’ function and cognition and contributes to the global disease burden [1]. The two most common types are Alzheimer’s disease (AD) and vascular dementia, which are reported to account for 70 to 90% of cases [2].

Dementia is a leading cause of morbidity and disability in developed countries and results in a greater financial burden on health and social care systems and the economy in general to a greater extent than cancer, cardiovascular disease, and stroke combined [3]. There are an estimated 44 million people around the world who have dementia, and the number is expected to triple by 2050 [4]. In Thailand, the prevalence of dementia in old adults reported between 1991 and 2008 ranged from two to ten percent, with the trend expected to double with every five-year increase in the age of people aged 65 and over [5].

Numerous patient characteristics, including age, gender, ethnicity, and comorbidity, have been identified as prognostic factors in patients with dementia. Various studies reported that differences in ethnicity affect dementia prognosis and mortality [6, 7]. Moreover, dementia has a more prevalent association with several health conditions [8, 9]. Cerebrovascular disease, cirrhosis, asthma, and diabetes mellitus have been significantly linked with mild cognitive impairment and dementia [10]. In addition, several comorbidities have been linked to increased mortality risk in individuals with dementia [11–19]. Characterization of dementia prognosis and the influence of prognostic factors is crucial information for the evaluation of and decision regarding disease management, communicating with patients and their relatives, and advanced care planning [20, 21]. In the Thai care Guidelines for Dementia, it is recommended that comorbidities, especially cardiovascular diseases and risks, should be well-controlled [22]. Research has shown that patient comorbidities need to be taken into consideration [23].

A review of the literature, however, has identified gaps in the evaluation of disease outcomes, which include mortality and comorbidities [24]. Details concerning the survival time and comorbidity-based prognosis of patients with dementia in Thailand are still relatively sparse. Therefore, the purpose of this study was to describe the ten-year survival probability and to identify comorbidities linked with ten-year survival in patients with dementia.

METHODS

This retrospective observational cohort study was conducted under review and approval from the Institutional Ethics Committee of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (Ethical approval number: 8932/2022).

Maharaj Nakorn Chiang Mai Hospital is a university-affiliated, tertiary care center in Northern Thailand. All patients with dementia are treated by neurologists and psychiatrists. Patients do not need appointments but can access walk-in care independently or can be referred from the other hospitals in northern Thailand. They usually have complex comorbidities with a variety of severity.

Study population and sample size calculation

The study population were those who had been diagnosed with dementia from the outpatient department at Maharaj Nakorn Chiang Mai Hospital between January 2006 and December 2012 (tracking from ICD-10 codes [25] as shown in Supplementary Table 1). The optimum sample size was calculated using Stata software based on a survival analysis formula. Effect sizes for the sample size calculation were determined by the hazard ratios of the prognostic factors from a previous study [26]. The event (death) probability of 73.26% was obtained from our previous survey of dementia patients. The data from at least 239 dementia patients would detect a hazard ratio of 1.5 with a statistical power of 80%. We decided to collect the data from the records of all eligible patient.

The data in the electronic medical records of all relevant patients was reviewed. We included all the patients who had visited the outpatient department at Maharaj Nakorn Chiang Mai Hospital and were diagnosed with any type of dementia by the neurologists. If there was adequate record, we confirmed the diagnosis according to the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) 2013 [27] and Thai Clinical Practice Guideline for Dementia [22]. The dementia diagnosis date would be the start date of the follow-up period. The data from patients with a prior diagnosis of dementia from other hospitals and no recorded data of diagnosis information, or reversible dementia, e.g., infectious process, an endocrine disorder, or nutritional deficiency, or incomplete demographic data (history of diagnosis of dementia, date of diagnosis of dementia, and death date) were excluded.

Variables and data sources

The secondary data of patients’ age, gender, date of dementia diagnosis and death, types of dementia, and comorbidities at the time of dementia diagnosis were assessed. The type of dementia was reviewed and confirmed by using the following criteria. With regard to types of dementia, NINCDS-ADRDA criteria were applied to identify possible or probable AD [28]. NINDS/AIREN criteria were used to diagnose possible vascular dementia [29]. Parkinson’s disease dementia (PDD) was diagnosed in accordance with clinical diagnostic criteria for dementia associated with Parkinson’s disease [30]. Dementia with Lewy bodies (DLB) was diagnosed in accordance with the Consortium on DLB [31]. Frontotemporal dementia (FTD) diagnostic criteria were taken from the Work Group on FTD and Pick’s disease [32]. Other types were defined as any PDD, DLB, or FTD. The mixed type was defined as the combination of two or more types of dementia. If the review is not possible, we used the original diagnosis available from the source document. Comorbidities were the patients’ underlying diseases at the time that dementia was diagnosed. The comorbidities selected to be included in the prognosis factor analysis were based on a review of previous literature. Comorbidities in the Charlson Comorbidities Index (CCI) [33] (including myocardial infarction [11, 13, 15, 17], congestive heart failure [13], peripheral vascular disease [17], cerebrovascular accident or transient ischemic attack [16, 17], chronic obstructive pulmonary disease, connective tissue disease, peptic ulcer disease, liver disease, diabetes mellitus [11, 15–17], moderate to severe chronic kidney disease, solid tumor [17], leukemia [18], lymphoma, and acquired immunodeficiency syndrome (AIDS), and also hypertension [19], Parkinson’s disease [13], atrial fibrillation [13], and any mental disorder [14, 17] (including, schizophrenia, bipolar I disorder, bipolar II disorder, major depressive disorder, and mood disorder) have been linked to an increased risk of dementia. The comorbidities were defined using ICD-10 codes [25] available in the electronic medical records (Supplementary Table 2). All-cause death status and death date was obtained from the Thai civil registration system database.

Statistical analysis

Statistical analyses were performed using STATA statistical software version 16. Categorical data were described using frequency and percentage. Normally distributed continuous data were described using mean and standard deviation while non-normally distributed data were described as median and interquartile range. Descriptive analysis was used to describe participants’ characteristics, the prevalence of comorbidities, and survival time. Survival time was determined as the duration between the date of dementia diagnosis and the date of death or the last date of the ascertainment period (1 February 2022). Overall survival analysis and Kaplan-Meier survival plot were performed to describe the ten-year survival probability. The association between comorbidities and the ten-year survival time was analyzed using a multivariable Cox proportional hazard model adjusted for age [34, 35], gender [36–38], types of dementia [39, 40], and other comorbidities. The adjustment effect of each confounder is shown in Supplementary Table 3. Age was grouped as in CCI, which are less than 50 years, 50– 59 years, 60– 69 years, 70– 79 years, and more than 80 years. Adjusted Hazard ratios (aHRs) and 95% confidence intervals (95% CI) were estimated to indicate the magnitude and strength of the associations. The proportional-hazards assumption was tested via an inspection of a graphical and a statistical analysis. The graphical tests: 1) a goodness-of-fit between observed (Kaplan-Meier plots) and predicted (Cox-regression curves) survival probabilities; and 2) Schoenfeld’s residual plots were assessed to assure that a proportional-hazards assumption was not violated. For statistical analysis, a goodness-of-fit (chi-squared) test of Schoenfeld’s residual for the overall (global test) and each variable was performed. The global test shows a p-value of 0.227. As a result, there was no evidence of a violation of the proportional-hazards assumption. The details of the tests of the proportional-hazards assumption are shown in Supplementary Figures 1 and 2. A subgroup analysis was conducted for AD and vascular dementia. The estimated associations were presented by a co-efficient plot with 95% CI. A p-value of less than 0.05 was used as a measure of statistically significance.

RESULTS

Patients’ characteristics and median overall survival

We reviewed 865 electronic medical records of data extracted using ICD-10 codes for dementia. There were 702 eligible patients with dementia who were included in the study and for analysis. There was no missing data. We were able to confirm the outcome of the participants. On average, the number of hospital visits was 14.58 (SD 31.90). The median follow-up time was 5.85 (IQR 2.98– 10.33). The total deaths at the end of the follow-up time were 536 (76.35%). Figure 1 shows the patient flow diagram. Of 702 patients, 56.9% were female. The mean age at diagnosis of dementia was 75.22 (SD 9.75) years old. The most prevalent dementia types were AD (39.6%) and vascular dementia (28.8%). The five most common comorbidities were hypertension (57.69%), dyslipidemia (35.75%), cerebrovascular accident or TIA (24.93%), type 2 diabetes mellitus (21.94%), and Parkinson’s disease (13.96%). Table 1 shows the baseline characteristics of the patients. The median overall survival was 6.0 years (95% CI 5.5– 6.7) (Fig. 2a). The survival probability by subtype of dementia was not significantly different, as shown in Fig. 2b.

Fig. 1

Flow diagram showing data distribution.

Table 1

Baseline Characteristics of Patients with Dementia

Characteristic N = 702	Total, n (%)	10-year overall survival, % (95% CI)	Crude hazard ratio	p
(95% CI)
Gender
Male	308 (43.87)	28.94 (23.94 – 34.12)	Ref
Female	394 (56.913)	33.99 (29.30 – 38.73)	0.88 (0.74 – 1.04)	0.140
Age y (Mean ± SD)	75.22±9.75
Type of dementia
Alzheimer’s disease	278 (39.60)	32.48 (26.98 – 38.10)	Ref
Vascular dementia	202 (28.77)	28.81 (22.71 – 35.18)	1.03 (0.84 – 1.27)	0.750
Mixed type	83 (11.82)	24.93 (16.21 – 34.62)	1.14 (0.87 – 1.49)	0.342
Others	48 (6.84)	36.89 (23.21 – 50.62)	1.06 (0.75 – 1.51)	0.731
Unspecified	91 (12.96)	40.00 (29.87 – 49.92)	0.86 (0.65 – 1.15)	0.317
Comorbidities
Cardiovascular disease
Atrial fibrillation	18 (2.56)	5.56 (0.37 – 22.42)	2.43 (1.52 – 3.90)	<0.001
Hypertension	405 (57.69)	32.48 (27.91 – 37.11)	0.96 (0.81 – 1.14)	0.623
Myocardial infarction	36 (5.13)	16.67 (6.76 – 30.36)	1.77 (1.24 – 2.53)	0.002
Congestive heart failure	25 (3.56)	10.67 (2.32 – 26.41)	2.00 (1.32 – 3.05)	0.001
Cerebrovascular accident or TIA	175 (24.93)	25.97 (19.71 – 32.65)	1.13 (0.93 – 1.37)	0.206
Peripheral vascular disease	24 (3.42)	29.71 (12.82 – 48.82)	0.99 (0.60 – 1.62)	0.956
Pulmonary disease
Chronic Obstructive Pulmonary Disease	24 (3.42)	16.67 (5.22 – 33.70)	2.03 (1.32 – 3.11)	0.001
Asthma	12 (1.71)	72.73 (37.08 – 90.28)	0.36 (0.15 – 0.87)	0.023
Gastrointestinal conditions
Peptic ulcer	4 (0.57)	50.00 (5.78 – 84.49)	0.38 (0.09 – 1.52)	0.170
Inflammatory bowel disease	1 (0.14)	0.00	0.75 (0.11 – 5.35)	0.776
Irritable bowel syndrome	3 (0.43)	66.67 (5.41 – 94.52)	0.29 (0.04 – 2.09)	0.221
Liver disease	12 (1.71)	8.33 (0.51 – 31.11)	2.19 (1.20 – 3.98)	0.010
Genitourinary system
Moderate to severe CKD	40 (5.70)	20.00 (9.39 – 33.45)	1.50 (1.06 – 2.12)	0.023
Musculoskeletal system
Connective tissue disease	2 (0.28)	0.00	2.05 (0.51 – 8.25)	0.310
Osteoporosis	10 (1.42)	24.00 (3.77 – 53.73)	1.32 (0.66 – 2.66)	0.433
Neuropsychiatric disorder
Parkinson’s disease	98 (13.96)	24.47 (16.29 – 33.56)	1.25 (0.98 – 1.58)	0.072
Any mental disorder	76 (10.83)	39.95 (28.85 – 50.79)	0.71 (0.53 – 0.95)	0.020
Metabolic and endocrine disorders
Type 2 Diabetes Mellitus	154 (21.94)	23.01 (16.62 – 30.03)	1.32 (1.08 – 1.61)	0.007
Dyslipidemia	251 (35.75)	33.03 (27.22 – 38.95)	1.01 (0.85 – 1.21)	0.889
Gout	24 (3.42)	34.47 (16.19– 53.62)	1.11 (0.69 – 1.77)	0.677
Hypothyroidism	9 (1.28)	33.33 (7.83 – 62.26)	1.14 (0.54 – 2.40)	0.730
Hyperthyroidism	8 (1.14)	50.00 (15.20 – 77.49)	0.89 (0.40 – 2.00)	0.784
Hematologic disease
Leukemia	1 (0.14)	0.00	0.63 (0.09 – 4.47)	0.643
Lymphoma	4 (0.57)	0.00	2.75 (1.03 – 7.37)	0.044
Infectious disease
AIDS	3 (0.43)	0.00	2.44 (0.78 – 7.59)	0.124
Other conditions
Solid tumor	37 (5.27)	29.73 (16.12 – 44.65)	1.14 (0.79 – 1.64)	0.498
SNHL	1 (0.14)	0.00	3.80 (0.53 – 27.15)	0.183
Cataract	12 (1.71)	25.00 (6.01 – 50.48)	1.14 (0.61 – 2.13)	0.683
Glaucoma	10 (1.42)	20.00 (3.09 – 47.47)	1.58 (0.82 – 3.06)	0.174
Psoriasis	2 (0.28)	50.00 (0.6 – 91.04)	0.91 (22.60 – 3.64)	0.890

AIDS, Acquired immunodeficiency syndrome; CI, confidence interval; CKD, chronic kidney disease; SD, standard deviation; SNHL, sensory neural hearing loss; TIA, transient ischemic attack.

Fig. 2

Overall survival time. CI, confidence interval.

Comorbidity and overall survival

The comorbidities associated with poor prognosis in all types of dementia included liver disease (aHR 2.70, 95% CI 1.46– 5.00), atrial fibrillation (aHR 2.15, 95% CI 1.29– 3.58), myocardial infarction (aHR 1.55, 95% CI 1.07– 2.26), and type 2 diabetes mellitus (aHR 1.40, 95% CI 1.13– 1.74). Hypertension was associated with a better overall prognosis (aHR 0.80, 95% CI 0.66– 0.96) (Fig. 3a). For the subgroup analysis of patients with AD, the comorbidity associated with poor prognosis included atrial fibrillation (aHR 3.54, 95% CI 1.10– 11.42), cerebrovascular disease or TIA (aHR 1.84, 95% CI 1.24– 2.73), and type 2 diabetes mellitus (aHR 1.57, 95% CI 1.06– 2.34) (Fig. 3b). In the case of vascular dementia, the comorbidities associated with poor prognosis included liver disease (aHR 3.32, 95% CI 1.28– 8.62), atrial fibrillation (aHR 4.80, 95% CI 1.93– 11.92), myocardial infarction (aHR 2.44, 95% CI 1.30– 4.58), and type 2 diabetes mellitus (aHR 2.08, 95% CI 1.44– 3.00) (Fig. 3c). The associations between comorbidities and mortality by subtype of dementia are presented in Supplementary Table 4.

Fig. 3

Comorbidity-based prognostic factors of mortality in patients with dementia. The hazard ratio was adjusted against age, gender, types of dementia, and comorbidities. CI, confidence interval; CKD, chronic kidney disease; TIA, transient ischemic attack.

To minimize the bias that an unmeasured confounder (i.e., severity or stage of dementia) could have on the reported association between the comorbidity and 10-year mortality in dementia, a sensitivity analysis was performed by calculating the e-values for the point estimate of a significant prognostic factor (Supplementary Table 5). This indicates that the association of significant prognostic factors (liver disease, atrial fibrillation and myocardial infarction) are relatively robust and unlikely to be explained away by the unmeasured confounder as it would require all remaining unmeasured confounding to have relatively large effect size (>2), which is uncommon in the biomedical literature [41]. However, E-values suggests that there is also the potential for residual confounders to affect the point estimates. From the previous study in low- to middle-income countries, the effect estimate between disease severity as measured by the Clinical Dementia Rating (CDR) and higher mortality risk in dementia was reported as HR 1.43 (95% CI 1.22– 1.63) [14], which is also under the threshold that we mentioned above.

DISCUSSION

This study describes the survival time in Thai patients with dementia and the comorbidities that influence disease prognosis. The median overall survival for people with dementia in this study was approximately six years. AD and vascular dementia were the most prevalent types. Liver disease, atrial fibrillation, myocardial infarction, and type 2 diabetes mellitus were the comorbidities that were significantly related to poor 10-year survival. In contrast, hypertension was linked to a more favorable outcome. These comorbidities also indicated a significant association with ten-year survival in subgroups of patients with AD and vascular dementia.

The demographic data of the study population shows some interesting issues. First, the proportion of females in this study (56.9%) was lower than in other previous studies. The potential reason for the different gender distribution compared to other study populations could be that we have included all types of dementia. In another study AD had a higher female prevalence than in males, whereas vascular dementia had a higher male prevalence than in females [42]. However, this gender proportion was similar to a previous study into the etiology of dementia in Thailand which also included all types of dementia [43]. Second, the low proportion of AD in this study (39.6%) could be due to AD being included in mixed and unspecified types. There were a number of patients who refused or had contraindication for further investigation. As a result, we were unable to determine the exact number of cases of AD.

We reported a comparatively similar survival time to many previous studies. The median survival period ranges from 3.3 to 11.7 years from the time of disease onset [44, 45]. The majority of research showed a median survival time of seven to ten years [46, 47]. A large cohort study in the United Kingdom reported that about a quarter of individuals with dementia died in the first year after being diagnosed, the death rate doubling in the next five years [48]. In our study, different dementia subtypes showed no difference in survival time. A previous study in Norway demonstrated that the patients with vascular dementia or dementia with Lewy bodies/Parkinson’s had shorter survival time in comparison to other types [39]. Another study in Spain reported that dementia with multiple etiologies and Parkinson-plus syndromes, a group of heterogenous degenerative neurological disorders which has the primary features of Parkinson’s disease and additional features such as dementia [49], have the worst prognosis regarding mortality [40]. The discordance of the results could be explained by the variation in population, race, or ethnicity [6, 7].

Comorbidities have been linked to increased risk of mortality in dementia [50, 51] and our study supported this statement. Evidence shows that the number of comorbidities itself increases the risk of death [52]. Multiple comorbidities are frequently followed by medication problems that also affect health outcomes, e.g., polypharmacy or risk of drug interactions [53]. However, when comorbidities occur together with dementia, the risk of mortality may double [54]. In patients with dementia, both cognition and daily functioning deteriorate. The ability to self-care is also affected, frequently contributing to difficulty in communication and clinical evaluation [55]. Many factors must be taken into account when making a care plan for patients with dementia and comorbidities [23]. Interestingly, in analysis models, as evidenced by the change of adjusted hazard ratios, it means that age, gender, types of dementia, and other confounders affect the association between comorbidity and 10-year mortality. Age is the covariate that affects the results more than others. Increasing age is associated with a higher risk of mortality in dementia [56].

There is a growing bank of evidence to suggest that chronic liver disease and liver cirrhosis are associated with increased mortality in dementias [12, 57]. Various studies found that viral hepatitis [58], primary biliary cirrhosis [59], and non-alcoholic fatty liver disease (NAFLD) [60–62] were correlated with the development of dementia. A network clustering study reported that NAFLD and AD share several related genes [63]. In addition changes in brain imaging were found in hepatitis C-infected patients [64, 65]; and a further study in non-genetic predisposition showed neurodegeneration can also be aggravated by chronic inflammation outside the brain, including in the liver [66].

Type 2 diabetes mellitus, a condition in which insulin is not efficiently used by the body’s cells, has been shown to have the relationship with mild cognitive impairment [67], AD, and vascular dementia [68, 69]. Insulin is crucial for many physiological processes, including brain function [70]. Insulin resistance has been connected to some neurodegenerative mechanisms, such as oxidative stress, mitochondrial dysfunction, and chronic liver inflammation [71, 72]. Microvascular damage in type 2 diabetes mellitus could decrease cognitive performance [73, 74]; the diabetes mellitus also showing an association with a shorter survival time in patients with dementia, especially in older adults [12, 75]. The potential explanation is a decline in cognition which disrupts the complexity of self-care tasks and the ability to maintain appropriate blood glucose levels [76]. Hyperglycemic and hypoglycemic complications may contribute to the increase in the risk for mortality [77, 78].

In patients with atrial fibrillation, individuals with dementia were associated with older age, a higher number of comorbidities, and shorter survival time compared with individuals without dementia [79]. The possible reasons are likely to be inadequate anticoagulant use and experience of an increase in thrombotic events. Dementia is a concern for healthcare professionals when making a treatment plan for patients with atrial fibrillation, the condition potentially affecting the reduction in warfarin prescription [80].

Previous research into the effect of dementia mortality and a history of myocardial infarction is limited. Previous studies have reported that coronary heart disease, including myocardial infarction, was associated with mortality in patients with dementia [17, 81]. Patients with dementia were also linked to a higher mortality rate and different care patterns after the onset of myocardial infarction [82]. These findings indicate that the higher mortality rate may be due to the nature of dementia and the level to which patients are involved in some level of dependent status [83]. They frequently need additional care from the caregiver and the healthcare team, particularly if they have more than one condition [17].

Unlike in previous literature [11, 84], our results showed a good prognosis in patients with dementia who had hypertension. This may be due to the effect of antihypertensive medications. A meta-analysis has shown that lowering blood pressure is correlated with a lower risk of developing dementia [85, 86]. This may imply a potential effect of antihypertensive medications on cognition. Additionally, a mortality risk reduction was found in hypertensive dementia patients who had received amlodipine, a calcium channel blocker medication [87]. However, in our study, we did not collect the type of medication, and hypertension was assessed only at the time of diagnosis, not during the lifetime. Further study on types of medication and latest blood pressure history, and their association with mortality risk is needed. However, a systematic review in 2016 [81] found that hypertension is not associated with mortality.

In the subgroup analysis, the results show the same trend of associations for atrial fibrillation, and type 2 diabetes mellitus. However, cerebrovascular accident or TIA in our study was linked with poor prognosis in the AD group. The synergistic effects of pathophysiology in AD brain and ischemic stroke lesions may worsen the disease outcome. A study in individuals with ischemic stroke reported that patients who had developed AD after the events showed a higher mortality rate than those with vascular dementia [88].

This is a relatively large study that reports survival time in Thai adults with dementia, and the diagnoses were validated based on extensive evidence in a tertiary care setting. However, the study comes with some limitations. First, the data were obtained retrospectively from electronic records. Only the information on recorded comorbidities was obtained and the details of some information were based on clinician notes. Some data were limiting as regards further review, for example, information for differentiating between HIV-associated dementia and HIV-associated neurocognitive disorders, or differentiating between Parkinson’s disease as a comorbid disease and PDD. In addition, the capturing of comorbidities in this data may not be robust. To illustrate this point, the prevalence of atrial fibrillation in our study was relatively low compared to the prevalence in previous studies of non-demented populations [89–91]. This may be due to underdetection or lack of recording. Nevertheless, we have confidence that the retrieved information is reliable because medical auditors have audited all the relevant medical records. Second, some information, such as the severity of cognitive impairment at the time of diagnosis, any comorbidity that occurred during the following period, or cause of death, was not obtained. However, we have conducted a sensitivity analysis to take account of unmeasured confounding factors. The results show that the effect of residual confounders was unlikely to be strong enough to be strong enough to explain away the association in the case of liver disease, atrial fibrillation, myocardial infarction. Further studies should consider these factors as potential prognostic in nature as regards life expectancy. Although AIDS was included in the analysis as a covariate and demonstrated statistical significance, we did not include it in the main results due to a small sample size (n = 3) and a high degree of uncertainty and bias. Third, the results may not be generalized for dementia patients in other settings because this study was conducted in a single hospital setting. A multicenter study or meta-analysis may further contribute to greater applicability and transferability taking into account that previous studies have been focused on other populations [7]. This study adds to the current drive in Alzheimer’s and dementia research by the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART) in ethnoracial populations. Finally, we cannot conclude from this study that the same comorbidities would be the cause of death in both dementia and non-dementia patients, as we only studied in patients with dementia.

Conclusion

The overall survival rate of patients with dementia in Thailand was comparable to previous studies. Several comorbidities, including liver disease, atrial fibrillation, myocardial infarction, and type 2 diabetes mellitus, were related to ten-year survival in patients with dementia, which raised the risk of all-cause mortality. The comprehensive and effective treatment of comorbidities may enhance the outcome of patients with dementia.

Footnotes

ACKNOWLEDGMENTS

The authors have no acknowledgments to report.

FUNDING

This work was partially supported by Chiang Mai University.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

DATA AVAILABILITY

The data supporting the findings of this study are available on request from the corresponding author. The data is not publicly available due to privacy or ethical restrictions.

The supplementary material is available in the electronic version of this article: .

References

Lane

, Hardy

, Schott

(2018) Alzheimer’s disease. Eur J Neurol 25, 59–70.

Rizzi

, Rosset

, Roriz-Cruz

(2014) Global epidemiology of dementia: Alzheimer’s and vascular types. Biomed Res Int 2014, 908915.

Luengo-Fernandez

, Leal

, Gray

(2012) UK research expenditure on dementia, heart disease, stroke and cancer: Are levels of spending related to disease burden? Eur J Neurol 19, 149–154.

Prince

, Ali

, Guerchet

, Prina

, Albanese

, Wu

(2016) Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 8, 23.

Prasat Neurological Institute, Department of Medical Services (2014) Clinical Practice Guidelines: Dementia Tana Press Co., Ltd, Bangkok.

Lewis

, Werbeloff

, Hayes

, Howard

, Osborn

DPJ

(2018) Diagnosed depression and sociodemographic factors as predictors of mortality in patients with dementia. Br J Psychiatry 213, 471–476.

Babulal

, Quiroz

, Albensi

, Arenaza-Urquijo

, Astell

, Babiloni

, Bahar-Fuchs

, Bell

, Bowman

, Brickman

, Chételat

, Ciro

, Cohen

, Dilworth-Anderson

, Dodge

, Dreux

, Edland

, Esbensen

, Evered

, Ewers

, Fargo

, Fortea

, Gonzalez

, Gustafson

, Head

, Hendrix

, Hofer

, Johnson

, Jutten

, Kilborn

, Lanctôt

, Manly

, Martins

, Mielke

, Morris

, Murray

, Oh

, Parra

, Rissman

, Roe

, Santos

, Scarmeas

, Schneider

, Schupf

, Sikkes

, Snyder

, Sohrabi

, Stern

, Strydom

, Tang

, Terrera

, Teunissen

, Melo

van Lent D

, Weinborn

, Wesselman

, Wilcock

, Zetterberg

, O’Bryant

(2019) Perspectives on ethnic and racial disparities in Alzheimer’s disease and related dementias: Update and areas of immediate need. Alzheimers Dement 15, 292–312.

Vassilaki

, Aakre

, Cha

, Kremers

, Sauver

St. , Mielke

, Geda

, Machulda

, Knopman

, Petersen

, Roberts

(2015) Multimorbidity and risk of mild cognitive impairment. J Am Geriatr Soc 63, 1783–1790.

Roberts

, Cha

, Mielke

, Geda

, Boeve

, Machulda

, Knopman

, Petersen

(2015) Risk and protective factors for cognitive impairment in persons aged 85 years and older. Neurology 84, 1854–1861.

10.

Chen

, Yiao

, Sun

, Lee

, Yang

, Chiu

, Chen

, Lin

, Tang

, Lin

, Wang

(2017) Comorbidity and dementia: A nationwide survey in Taiwan. PLoS One 12, e0175475.

11.

Helzner

, Scarmeas

, Cosentino

, Tang

, Schupf

, Stern

(2008) Survival in Alzheimer disease: A multiethnic, population-based study of incident cases. Neurology 71, 1489–1495.

12.

Kim

, Lee

, Han

, Lee

, Kang

, Kim

, Cha

(2017) Impact of diabetes mellitus and chronic liver disease on the incidence of dementia and all-cause mortality among patients with dementia. Medicine (Baltimore) 96, e8753.

13.

Van Dijk

, Dippel

, Van Der Meulen

, Habbema

(1996) Comorbidity and its effect on mortality in nursing home patients with dementia. J Nerv Ment Dis 184, 180–187.

14.

Piovezan

, Oliveira

, Arias

, Acosta

, Prince

, Ferri

(2020) Mortality rates and mortality risk factors in older adults with dementia from low- and middle-income countries: The 10/66 Dementia Research Group Population-Based Cohort Study. J Alzheimers Dis 75, 581–593.

15.

Larson

, Shadlen

, Wang

, McCormick

, Bowen

, Teri

, Kukull

(2004) Survival after initial diagnosis of Alzheimer disease. Ann Intern Med 140, 501–509.

16.

Steenland

, MacNeil

, Seals

, Levey

(2010) Factors affecting survival of patients with neurodegenerative disease. Neuroepidemiology 35, 28–35.

17.

Rajamaki

, Hartikainen

, Tolppanen

(2021) The effect of comorbidities on survival in persons with Alzheimer’s disease: A matched cohort study. BMC Geriatr 21, 173.

18.

Marsilli

, Funtowicz

, Epstein

, Giunta

, Peroni

, Vergara

(2022) [Mortality in patients with dementia admitted in critical care units]. Rev Esp Geriatr Gerontol 57, 150–155.

19.

Meerman

, van de Lisdonk

, Koopmans

, Zielhuis

, Olde

Rikkert MG

(2008) Prognosis and vascular co-morbidity in dementia a historical cohort study in general practice. J Nutr Health Aging 12, 145–150.

20.

Mountford

, Dening

, Green

(2020) Advance care planning and decision-making in dementia care: A literature review. Nurs Older People, doi: 10.7748/nop.2020.e1238.

21.

Arvanitakis

, Shah

, Bennett

(2019) Diagnosis and management of dementia: Review. JAMA 322, 1589–1599.

22.

Neurological Institute of Thailand, Department of Medical Services (2020) Thai Clinical practice guideline for Dementia, Neurological Institute of Thailand.

23.

Santiago

, Potashkin

(2021) The impact of disease comorbidities in Alzheimer’s disease. Front Aging Neurosci 13, 631770.

24.

Snowden

, Steinman

, Bryant

, Cherrier

, Greenlund

, Leith

, Levy

, Logsdon

, Copeland

, Vogel

, Anderson

, Atkins

, Bell

, Fitzpatrick

(2017) Dementia and co-occurring chronic conditions: A systematic literature review to identify what is known and where are the gaps in the evidence? Int J Geriatr Psychiatry 32, 357–371.

25.

Centers for Medicare & Medicaid Services (U.S.), National Center for Health Statistics (U.S.) (2022), ICD-10-CM Official Guidelines for Coding and Reporting.

26.

Sampson

, Leurent

, Blanchard

, Jones

, King

(2013) Survival of people with dementia after unplanned acute hospital admission: A prospective cohort study. Int J Geriatr Psychiatry 28, 1015–1022.

27.

American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

28.

McKhann

, Drachman

, Folstein

, Katzman

, Price

, Stadlan

(1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34, 939–944.

29.

Roman

, Tatemichi

, Erkinjuntti

, Cummings

, Masdeu

, Garcia

, Amaducci

, Orgogozo

J-M

, Brun

, Hofman

, Moody

, O’Brien

, Yamaguchi

, Grafman

, Drayer

, Bennett

, Fisher

, Ogata

, Kokmen

, Bermejo

, Wolf

, Gorelick

, Bick

, Pajeau

, Bell

, DeCarli

, Culebras

, Korczyn

, Bogousslavsky

, Hartmann

, Scheinberg

(1993) Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43, 250–260.

30.

Emre

, Aarsland

, Brown

, Burn

, Duyckaerts

, Mizuno

, Broe

, Cummings

, Dickson

, Gauthier

, Goldman

, Goetz

, Korczyn

, Lees

, Levy

, Litvan

, McKeith

, Olanow

, Poewe

, Quinn

, Sampaio

, Tolosa

, Dubois

(2007) Clinical diagnostic criteria for dementia associated with Parkinson’s disease.1689-1707; quiz. Mov Disord 22, 1837.

31.

Geser

, Wenning

, Poewe

, McKeith

(2005) How to diagnose dementia with Lewy bodies: State of the art.S. Mov Disord 20(Suppl 12), 11–20.

32.

McKhann

, Albert

, Grossman

, Miller

, Dickson

, Trojanowski

(2001) Clinical and pathological diagnosis of frontotemporal dementia: Report of the Work Group on Frontotemporal Dementia and Pick’s Disease. Arch Neurol 58, 1803–1809.

33.

Lopes

BNA

, Garcez

, Suemoto

, Morillo

(2022) Accuracy of two prognostic indexes to predict mortality in older adults with advanced dementia. Dement Neuropsychol 16, 52–60.

34.

Schäufele

, Bickel

, Weyerer

(1999) Predictors of mortality among demented elderly in primary care. Int J Geriatr Psychiatry 14, 946–956.

35.

Ganguli

, Dodge

, Shen

, Pandav

, DeKosky

(2005) Alzheimer disease and mortality: A 15-year epidemiological study. Arch Neurol 62, 779–784.

36.

Xie

, Brayne

, Matthews

(2008) Survival times in people with dementia: Analysis from population based cohort study with 14 year follow-up. BMJ 336, 258–262.

37.

Heyman

, Peterson

, Fillenbaum

, Pieper

(1996) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part XIV. Neurology 46, 656–660.

38.

Mölsä

, Marttila

, Rinne

(1995) Long-term survival and predictors of mortality in Alzheimer’s disease and multi-infarct dementia. Acta Neurol Scand 91, 159–164.

39.

Strand

, Knapskog

, Persson

, Edwin

, Amland

, Mjørud

, Bjertness

, Engedal

, Selbæk

(2018) Survival and years of life lost in various aetiologies of dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) in Norway. PLoS One 13, e0204436.

40.

Garre-Olmo

, Ponjoan

, Inoriza

, Blanch

, Sánchez-Pérez

, Cubí

, de Eugenio

, Turró-Garriga

, Vilalta-Franch

(2019) Survival, effect measures, and impact numbers after dementia diagnosis: A matched cohort study. Clin Epidemiol 11, 525–542.

41.

VanderWeele

, Ding

(2017) Sensitivity analysis in observational research: Introducing the E-Value. Ann Intern Med 167, 268–274.

42.

Cao

, Tan

C-C

, Xu

, Hu

, Cao

X-P

, Dong

, Tan

, Yu

J-T

(2020) The prevalence of dementia: A systematic review and meta-analysis. J Alzheimers Dis 73, 1157–1166.

43.

Dharmasaroja

, Assanasen

, Pongpakdee

, Jaisin

, Lolekha

, Phanasathit

, Cheewakriengkrai

, Chotipanich

, Witoonpanich

, Pitiyarn

, Lertwilaiwittaya

, Dejthevaporn

, Limwongse

, Phanthumchinda

(2021) Etiology of dementia in Thai patients. Dement Geriatr Cogn Dis Extra 11, 64–70.

44.

Wolfson

, Wolfson

, Asgharian

, M’Lan

, Ostbye

, Rockwood

, Hogan

(2001) A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 344, 1111–1116.

45.

Roberson

, Hesse

, Rose

, Slama

, Johnson

, Yaffe

, Forman

, Miller

, Trojanowski

, Kramer

, Miller

(2005) Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 65, 719–725.

46.

Todd

, Barr

, Roberts

, Passmore

(2013) Survival in dementia and predictors of mortality: A review. Int J Geriatr Psychiatry 28, 1109–1124.

47.

Liang

, Li

, Yang

, Tseng

, Carvalho

, Stubbs

, Thompson

, Mueller

, Shin

, Radua

, Stewart

, Rajji

, Tu

, Chen

, Yeh

, Tsai

, Yu

, Pan

, Chu

(2021) Mortality rates in Alzheimer’s disease and non-Alzheimer’s dementias: A systematic review and meta-analysis. Lancet Healthy Longev 2, e479–e488.

48.

Chung

, Providencia

, Sofat

, Pujades-Rodriguez

, Torralbo

, Fatemifar

, Fitzpatrick

, Taylor

, Li

, Dale

, Rossor

, Acosta-Mena

, Whittaker

, Denaxas

(2023) Incidence, morbidity, mortality and disparities in dementia: A population linked electronic health records study of 4.3 million individuals. Alzheimers Dement 19, 123–135.

49.

Mitra

, Gangopadhaya

, Das

(2003) Parkinsonism plus syndrome–a review. Neurol India 51, 183–188.

50.

Agüero-Torres

, Fratiglioni

, Guo

, Viitanen

, Winblad

(1998) Prognostic factors in very old demented adults: A seven-year follow-up from a population-based survey in Stockholm. J Am Geriatr Soc 46, 444–452.

51.

Agüero-Torres

, Fratiglioni

, Guo

, Viitanen

, Winblad

(1999) Mortality from dementia in advanced age: A 5-year follow-up study of incident dementia cases. J Clin Epidemiol 52, 737–743.

52.

, Zhang

, Hu

, Zhao

, Guo

, Shi

, Zhao

, Yin

, Shi

(2021) Relationship between multimorbidity, disease cluster and all-cause mortality among older adults: A retrospective cohort analysis. BMC Public Health 21, 1080.

53.

Nobili

, Garattini

, Mannucci

(2011) Multiple diseases and polypharmacy in the elderly: Challenges for the internist of the third millennium. J Comorb 1, 28–44.

54.

Taudorf

, Nørgaard

, Brodaty

, Laursen

, Waldemar

(2021) Dementia increases mortality beyond effects of comorbid conditions: A national registry-based cohort study. Eur J Neurol 28, 2174–2184.

55.

Banovic

, Zunic

, Sinanovic

(2018) Communication difficulties as a result of dementia. Mater Sociomed 30, 221–224.

56.

Gao

, Liu

(2021) Secular trends in the incidence of and mortality due to Alzheimer’s disease and other forms of dementia in China From 1990 to 2019: An age-period-cohort study and joinpoint analysis. Front Aging Neurosci 13, 709156.

57.

Lee

, Hsu

, Chou

, Yiin

, Muo

, Lin

(2018) Estimating the survival of elderly patients diagnosed with dementia in Taiwan: A longitudinal study. PLoS One 13, e0178997.

58.

Weissenborn

, Tryc

, Heeren

, Worthmann

, Pflugrad

, Berding

, Bokemeyer

, Tillmann

, Goldbecker

(2009) Hepatitis C virus infection and the brain. Metab Brain Dis 24, 197–210.

59.

Newton

, Hollingsworth

, Taylor

, El-Sharkawy

, Khan

, Pearce

, Sutcliffe

, Okonkwo

, Davidson

, Burt

, Blamire

, Jones

(2008) Cognitive impairment in primary biliary cirrhosis: Symptom impact and potential etiology. Hepatology 48, 541–549.

60.

Kim

, Oh

, Kim

, Jeong

, Oh

, Lee

, Park

, Shim

(2022) Association between non-alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study. Liver Int 42, 1027–1036.

61.

Jeong

, Oh

, Choi

, Chang

, Kim

, Son

, Lee

, Ahn

, Lee

, Koo

, Kim

, Park

(2022) Association of non-alcoholic fatty liver disease with incident dementia later in life among elder adults. Clin Mol Hepatol 28, 510–521.

62.

Shang

, Widman

, Hagström

(2022) Nonalcoholic fatty liver disease and risk of dementia: A population-based cohort study. Neurology 99, e574–e582.

63.

Karbalaei

, Allahyari

, Rezaei-Tavirani

, Asadzadeh-Aghdaei

, Zali

(2018) Protein-protein interaction analysis of Alzheimer‘s disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterol Hepatol Bed Bench 11, 27–33.

64.

Weissenborn

, Ennen

, Bokemeyer

, Ahl

, Wurster

, Tillmann

, Trebst

, Hecker

, Berding

(2006) Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment. Gut 55, 1624–1630.

65.

Forton

, Allsop

, Main

, Foster

, Thomas

, Taylor-Robinson

(2001) Evidence for a cerebral effect of the hepatitis C virus. Lancet 358, 38–39.

66.

Kim

, Krenz

, Toussaint

, Maurer

, Robinson

, Yan

, Torres

, Bynoe

(2016) Non-alcoholic fatty liver disease induces signs of Alzheimer’s disease (AD) in wild-type mice and accelerates pathological signs of AD in an AD model. J Neuroinflammation 13, 1.

67.

Luchsinger

, Reitz

, Patel

, Tang

, Manly

, Mayeux

(2007) Relation of diabetes to mild cognitive impairment. Arch Neurol 64, 570–575.

68.

Peila

, Rodriguez

, Launer

(2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes 51, 1256–1262.

69.

Ahtiluoto

, Polvikoski

, Peltonen

, Solomon

, Tuomilehto

, Winblad

, Sulkava

, Kivipelto

(2010) Diabetes, Alzheimer disease, and vascular dementia: A population-based neuropathologic study. Neurology 75, 1195–1202.

70.

Fernandez

, Torres-Alemán

(2012) The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci 13, 225–239.

71.

de la Monte

, Tong

(2014) Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem Pharmacol 88, 548–559.

72.

de la Monte

(2017) Insulin resistance and neurodegeneration: Progress towards the development of new therapeutics for Alzheimer’s disease. Drugs 77, 47–65.

73.

Hugenschmidt

, Lovato

, Ambrosius

, Bryan

, Gerstein

, Horowitz

, Launer

, Lazar

, Murray

, Chew

, Danis

, Williamson

, Miller

, Ding

(2014) The cross-sectional and longitudinal associations of diabetic retinopathy with cognitive function and brain MRI findings: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 37, 3244–3252.

74.

Barzilay

, Lovato

, Murray

, Williamson

, Ismail-Beigi

, Karl

, Papademetriou

, Launer

(2013) Albuminuria and cognitive decline in people with diabetes and normal renal function. Clin J Am Soc Nephrol 8, 1907–1914.

75.

Zilkens

, Davis

, Spilsbury

, Semmens

, Bruce

(2013) Earlier age of dementia onset and shorter survival times in dementia patients with diabetes. Am J Epidemiol 177, 1246–1254.

76.

Hopkins

, Shaver

, Weinstock

(2016) Management of adults with diabetes and cognitive problems. Diabetes Spectr 29, 224–237.

77.

Liu

C-L

, Lin

M-Y

, Hwang

S-J

, Liu

C-K

, Lee

H-L

, Wu

M-T

(2019) Association of hyperglycemia episodes on long-term mortality in type 2 diabetes mellitus with vascular dementia: A population-based cohort study. J Diabetes Complications 33, 123–127.

78.

Han

, Han

, Lee

, Kang

, Cha

, Ko

, Lee

(2022) Severe hypoglycemia increases dementia risk and related mortality: A nationwide, population-based cohort study. J Clin Endocrinol Metab 107, e1976–e1986.

79.

Jurin

, Lucijanić

, Radonić

, Letilović

, Pejić

, Lucijanić

, Tješić-Drinković

, Sokol

Tomić S

, Hadžibegović

(2022) Patients with dementia and atrial fibrillation less frequently receive direct oral anticoagulants (DOACs) and experience higher thrombotic and mortality risk. Acta Clin Belg 77, 565–570.

80.

Scowcroft

, Lee

, Mant

(2013) Thromboprophylaxis of elderly patients with AF in the UK: An analysis using the General Practice Research Database (GPRD) 2000-2009. Heart 99, 127–132.

81.

van de Vorst

, Koek

, de Vries

, Bots

, Reitsma

, Vaartjes

(2016) Effect of vascular risk factors and diseases on mortality in individuals with dementia: A systematic review and meta-analysis. J Am Geriatr Soc 64, 37–46.

82.

Sloan

, Trogdon

, Curtis

, Schulman

(2004) The effect of dementia on outcomes and process of care for Medicare beneficiaries admitted with acute myocardial infarction. J Am Geriatr Soc 52, 173–181.

83.

Cunningham

, McGuinness

, Herron

, Passmore

(2015) Dementia. Ulster Med J 84, 79–87.

84.

Warchol-Celinska

, Styczynska

, Prejbisz

, Przybylowska

, Chodakowska-Zebrowska

, Kurjata

, Piotrowski

, Polakowska

, Kabat

, Zdrojewski

, Drygas

, Januszewicz

, Barcikowska

(2015) Hypertension in patients with Alzheimer’s disease–prevalence, characteristics, and impact on clinical outcome. Experience of one neurology center in Poland. J Am Soc Hypertens 9, 711–724.

85.

Peters

, Beckett

, Forette

, Tuomilehto

, Clarke

, Ritchie

, Waldman

, Walton

, Poulter

, Ma

, Comsa

, Burch

, Fletcher

, Bulpitt

(2008) Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): A double-blind, placebo controlled trial. Lancet Neurol 7, 683–689.

86.

Poon

(2008) Effects of antihypertensive drug treatment on the risk of dementia and cognitive impairment. Pharmacotherapy 28, 366–375.

87.

Kalar

, Xu

, Secnik

, Schwertner

, Kramberger

, Winblad

, von Euler

, Eriksdotter

, Garcia-Ptacek

(2021) Calcium channel blockers, survival and ischaemic stroke in patients with dementia: A Swedish registry study. J Intern Med 289, 508–522.

88.

Zupanic

, von Euler

, Winblad

, Xu

, Secnik

, Kramberger

, Religa

, Norrving

, Garcia-Ptacek

(2021) Mortality after ischemic stroke in patients with Alzheimer’s disease dementia and other dementia disorders. J Alzheimers Dis 81, 1253–1261.

89.

Suwanwela

, Chutinet

, Autjimanon

, Ounahachok

, Decha-umphai

, Chockchai

, Indrabhakti

, Kijpaisalratana

, Akarathanawat

, Travanichakul

, Kitjavijitre

, Vongvasinkul

, Kanacharoen

, Bunlikitkul

, Charnwut

, Lowres

, Freedman

(2021) Atrial fibrillation prevalence and risk profile from novel community-based screening in Thailand: A prospective multi-centre study. Int J Cardiol Heart Vasc 32, 100709.

90.

Islam

, Poly

, Walther

, Yang

, Wu

, Lin

, Chien

, Li

(2019) Association between atrial fibrillation and dementia: A meta-analysis. Front Aging Neurosci 11, 305.

91.

Alam

, Kulshreshtha

, Li

, Subramanya

, Alonso

(2022) Associations of atrial fibrillation with mild cognitive impairment and dementia: An investigation using SPRINT research materials. J Clin Med 11, 5800.