Coexistence of somatic and psychological symptoms of depression among community-dwelling older adults is associated with the incidence of dementia

Abstract

Background

Depression in old age is associated with the incidence of dementia. However, whether a combination of somatic and psychological symptoms influences the risk of dementia has not been fully investigated.

Objective

We aimed to determine the association between the combination of psychological and somatic symptoms of depression and the incidence of dementia.

Methods

This prospective cohort study included 2111 community-dwelling older adults (median age = 73 years, interquartile range = 68–78 years, 39.5% male). Participants were evaluated for 5 years from baseline to assess the incidence of dementia. Somatic symptoms were defined as the presence of one or more symptoms of fatigue, weight loss, sleep disturbances, and abnormal appetite. Psychological symptoms were assessed using the 15-item Geriatric Depression Scale. Participants were stratified into four groups based on the presence or absence of somatic and psychological symptoms. A Cox proportional hazards model was used to examine the associations with the incidence of dementia, adjusted for potential confounders.

Results

The hazard ratios for the incidence of dementia in the somatic (HR 1.42, 95% CI: 0.96–2.09) and psychological symptoms-only groups (HR 1.47, 95% CI: 0.83–2.59) were not significantly different; however, they were significantly higher in the coexistent group than in the normal group (HR 1.91, 95% CI: 1.24–2.94).

Conclusions

The coexistence of somatic and psychological symptoms of depression increases the risk of dementia. Therefore, interventions should consider both somatic and psychological symptoms to prevent or delay dementia.

Keywords

Alzheimer's disease depression psychological symptoms somatic symptoms

Introduction

The global prevalence of dementia is increasing as a result of the aging population.¹ Dementia, an urgent public health problem, affects individuals with the disease, their caregivers and families, and the socio-economic aspects.² Therefore, considering effective strategies to prevent or delay the incidence of dementia is important.

Several meta-analyses have reported that depression in old age is a risk factor for dementia.^3,4 These findings highlight the substantial impact of depression on the risk and management of dementia. However, findings from community-based cohort studies have been inconsistent. Some studies have reported that depression are associated with the risk of dementia.^5–7 However, other studies have found no association between depression and dementia in community-dwelling older adults.^8–10 This may be due to the difference in the assessment methods of depressive symptoms. Designed to measure depressive symptoms in the general population and widely used in both clinical and research settings, the Center for Epidemiological Studies - Depression (CES-D) includes questions about sleep and appetite as physical symptoms.¹¹ The Geriatric Depression Scale (GDS), designed to identify depressive symptoms in older adults, solely assesses only psychological symptoms.^12–14 Moreover, several scales used to assess depressive symptoms either include only some somatic symptoms commonly observed in depression or do not include them at all.

Typical symptoms of depression include psychological symptoms, such as mood changes, lack of motivation, and affective disorders, and somatic symptoms, such as fatigue, weight loss, sleep disturbances, and abnormal appetite. Depression is diagnosed when both somatic and psychological symptoms are present simultaneously. Therefore, it is important to focus on both the somatic and psychological aspects of depressive symptoms. Each somatic symptom is reportedly a risk factor for dementia.^15–19 However, whether somatic and psychological aspects are assessed separately in older adults and whether their combination has an effect on the incidence of dementia are yet to be further investigated. Older adults with depression are more likely than younger adults to report somatic symptoms as their primary complaint and not psychological symptoms.^20–22 Considering the psychological characteristics of older adults, it is important to focus on both the somatic and psychological aspects of depressive symptoms as risk factors for dementia. Therefore, we aimed to determine the relationship between the combination of psychological and somatic aspects of depressive symptoms and the incidence of dementia. We hypothesized that having both somatic and psychological symptoms would be associated with a higher risk of dementia incidence. The clarification of the association between the involvement of both the somatic and psychological symptoms and dementia risk would help to establish effective strategies to prevent or delay dementia in older adults with depressive symptoms.

Methods

Study design and participants

This study included older, community-dwelling, Japanese adults enrolled in the National Center for Geriatrics and Gerontology Study of Geriatric Syndrome.²³ Inclusion criteria were residents of Takahama City, Japan, aged 65 years or older at baseline. The inclusion criterion is set at age 65 or older because, in Japan, all adults aged 65 or older are covered by public medical insurance and can receive public services through the long-term care insurance system. We included 3353 participants from a health checkup conducted between September 2015 and June 2016. After the baseline assessment, individuals with a self-reported history of stroke (n = 214), Parkinson's disease (n = 15), dementia (n = 7), or major depression (n = 74) were excluded. These diseases were excluded owing to their disease-specific effects on depressive symptoms and dementia. As this study focused on depressive symptoms, major depression was also excluded. We also excluded those who required assistance with basic activities of daily life (n = 14) and had Mini-Mental State Examination (MMSE)²⁴ scores of <23 points (n = 316). Furthermore, those with missing data (n = 602) were excluded. Finally, data from 2111 participants aged 65–95 years were analyzed. All the participants provided written and informed consent. The study protocol followed the principles of the Declaration of Helsinki and was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology (Approval No.: 1440-5).

Assessment of somatic aspects of depressive symptoms

The participants’ perceived somatic symptoms were assessed at baseline. Typical somatic symptoms of depression include fatigue, weight loss, sleep disturbances, and abnormal appetite. Currently, no scale can comprehensively assess the four typical somatic symptoms of depression. Therefore, we selected questions that could assess these symptoms based on previous research. Fatigue and weight loss were rated as “present” if participants answered “yes” to the questions, “In the past 2 weeks, have you felt tired without a reason?” and “Have you lost 2 kg or more in the past 6 months?”, respectively.²⁵ Sleep disturbances were assessed using the question “Do you have sleep problems that reduce your motivation and concentration and limit your daily activities?”. According to the DSM-5 criteria, chronic insomnia is diagnosed when there are subjective reports of sleep complaints and daytime functional impairments such as fatigue, attention deficits, mood changes, and poor performance.²⁶ This question was selected to assess sleep disturbances that interfere with daily life, and not simply sleeplessness. Responses included “Not at all,” “Less than 1 day per week,” “1 or 2 times a week,” and “3 or more days per week.” Those who selected answers other than “not at all” were considered to be suffering from a sleep disorder. Abnormal appetite was assessed via the question “When I eat”, with the following options as responses: A. I feel full after eating only a few mouthfuls, B. I feel full after eating about a third of a plate/meal, C. I feel full after eating over half of a plate/meal, D. I feel full after eating most of the food, or E. I hardly ever feel full. This question was selected from the simplified nutritional appetite questionnaire²⁷ because older adults can answer this question about abnormal appetite based on their daily eating habits. Those who selected an option other than D were considered to have an abnormal appetite. Subsequently, the number of applicable somatic symptoms was added up.

The area under the curve (AUC) was calculated using a receiver operating characteristic (ROC) curve analysis to determine the cut-off values for physical symptoms that differed between participants currently diagnosed with depression and those who were not. The diagnosis of depression was based on self-report by the participant during the baseline assessment. Optimal cut-off values were obtained from the maximal Youden's index, calculated as (sensitivity + specificity − 1). If the number of somatic symptoms was greater than the determined cut-off, the participant was defined as having somatic symptoms.

Assessment of psychological aspects of depressive symptoms

Psychological symptoms were measured at baseline using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15).^12–14 The GDS-15 was developed to assess depression in older adults via self-administered surveys and was rated with binary yes (1) or no (0) answers. The total score ranged from 0–15 points, and higher scores indicated greater depression. We used a score of 5 or more to categorize depression, which was generally accepted as indicative of depressive tendencies, based on previous research.²⁸

Measurement of the incidence of dementia

Participants were evaluated for five years from baseline to assess the incidence of dementia. Participants were identified as having dementia based on either the corresponding code from the International Classification of Diseases-10 (ICD-10) or the Long-Term Care Insurance (LTCI) System Dementia Rating Scale used in Japan. The incidence of dementia was defined as a new diagnosis during the five-year follow-up period. Follow-up of dementia incidence based on ICD-10 codes and the LTCI system has been conducted in previous studies.^29,30 The details are described in the subsequent sections.

Dementia follow-up according to the ICD-10

In Japan, all adults aged ≥65 years have public health insurance, which includes health insurance for employed individuals (Employees’ Health Insurance), national health insurance for unemployed and self-employed individuals aged <75 years (Japanese National Health Insurance, JNHI), and healthcare for individuals aged >75 years (Later-Stage Medical Care: LSMC). We evaluated participants monthly for new-onset dementia (Alzheimer's disease, vascular dementia, frontotemporal dementia, and other subtypes) recorded by the National Health Insurance and Late-Stage Medical Care System. Participants were considered to have dementia based on a diagnosis made by a physician according to the ICD-10. The ICD-10 codes that we used to identify the incidence of dementia were based on criteria for the diagnosis of dementia from UK Biobank inpatient data. According to a previous study, the positive predictive rate of dementia was 87.3% when compared with the clinical expert adjudication of full-text medical records.³¹

Dementia follow-up through the LTCI system

The LTCI, a mandatory form of social insurance, supports older adults with disabilities.^32–34 In Japan, all individuals aged 65 and older are eligible for institutional or community-based services based on their disability level. The process of disability certification comprises an investigation of the degree of disability via a questionnaire developed by the Ministry of Health, Labor, and Welfare and a written opinion by an attending physician.³⁵ During the disability certification process, dementia is certified based on the Dementia Rating Scale (level of independence in daily living among older adults with dementia).³⁶ The Dementia Scale is classified into six ranks (0, I–IV, M), and patients with mild or moderate dementia are ranked as II. We defined the incidence of dementia as rank II or higher, derived from the written opinion of a primary care physician. This criterion has also been used in previous studies in Japan.^37,38 Regarding the validation of the Dementia Rating Scale, a previous study showed that it was well correlated with the MMSE (r = −0.736).³⁹ Another study reported that it was associated with dementia, as classified by the Clinical Dementia Rating.⁴⁰

Potential confounding factors

Potential confounders included age, sex, years of education, body mass index, chronic diseases (hypertension, diabetes, hyperlipidemia, heart disease, and respiratory disease), number of medications, drinking and smoking habits (current or not), cognitive function, and grip strength, based on a previous study.⁴¹ Cognitive function was assessed using the MMSE.²⁴ Participants’ dominant hand grip strength was measured using a Smedley-type hand-held dynamometer (GRIP-D; Takei Scientific Instruments Co, Ltd, Niigata, Japan). All assessments were conducted by trained research assistants. Participants’ medical information, such as their medical history, was obtained via face-to-face interactions with nurses.

Statistical analysis

The normality of the data was verified using the Shapiro–Wilk test. The non-parametric Kruskal–Wallis test was used, due to all non-normally distributed scores. A chi-squared (χ²) test was used to compare the categorical variables. Two Cox proportional hazards regression models were used to analyze whether the presence of psychological and somatic symptoms, as defined by the GDS scores and cut-off values determined by ROC analysis, respectively, were associated with the incidence of dementia. Subsequently, participants were classified into four groups based on the presence or absence of somatic and psychological symptoms. Furthermore, the incidence rate of dementia per 1000 person-years was calculated. A Cox proportional hazards regression model was used to examine the association between the combination of somatic and psychological symptoms (normal group with neither psychological nor somatic symptoms as a reference) and time of the incidence of dementia. Data that was lost during follow-up due to death or relocation was entered into the model as censored data. Statistical significance was set as 2-sided p-values of <0.05. All statistical analyses were conducted using IBM SPSS version 29 (IBM Japan, Tokyo, Japan).

Results

Optimum cut-off point for somatic symptoms

Of the 3353 participants, 3117 were included in the ROC curve analysis, after excluding those with a history of stroke (n = 214), Parkinson's disease (n = 15), or dementia (n = 7). The Youden Index approach for the ROC curve analysis indicated that the optimum cut-off point to discriminate between participants with (n = 38) and without (n = 3079) depression was ≥1 (AUC 0.63, 95% confidence interval [CI] 0.54–0.73; sensitivity, 63.2%; specificity, 57.7%).

Risk of dementia according to somatic and psychological symptoms

Data from 2111 older adults (834 males; median age = 73 years, interquartile range = 68–78 years) were analyzed. Tables 1 and 2 present the Cox proportional hazards regression model for each somatic and psychological symptom for the incidence of dementia. Participants with somatic symptoms had a higher risk of dementia incidence than participants without symptoms, even after adjusting for potential confounding factors (hazard ratio [HR] 1.46, 95% CI: 1.06–2.02) (Table 1). Similarly, participants with psychological symptoms had a higher risk of dementia incidence than participants without symptoms, even after adjusting for potential confounding factors (HR 1.48, 95% CI: 1.06–2.06) (Table 2).

Table 1.

Association between the somatic symptoms of depression and risk of dementia.

	Crude model			Adjusted model*
	HR	95% CI	p	HR	95% CI	p
Presence of Somatic Symptoms
No	1.00	(Reference)		1.00	(Reference)
Yes	2.24	1.64–3.06	<0.001	1.46	1.06–2.02	0.021
Covariates
Age				1.17	1.13–1.20	<0.001
Sex				1.65	1.02–2.68	0.042
Education				1.05	0.98–1.13	0.163
Body mass index				0.99	0.94–1.04	0.716
MMSE score				0.94	0.87–1.03	0.175
Grip strength				0.92	0.89–0.95	<0.001
Number of medications				1.13	1.07–1.20	<0.001
Hypertension				0.81	0.58–1.14	0.223
Diabetes				1.12	0.74–1.69	0.609
Hyperlipidemia				0.77	0.54–1.10	0.150
Heart diseases				0.52	0.33–0.82	0.005
Respiratory disease				0.82	0.49–1.37	0.443
Current smoker				1.99	1.07–3.71	0.030
Current alcohol drinker				0.72	0.48–1.10	0.135

HR: hazard ratio; CI: confidence interval.

*Adjusted for age, sex, years of education, body mass index, cognitive function, grip strength, number of medications, medical history, smoking habits, and alcohol consumption.

Table 2.

Association between the psychological symptoms of depression and risk of dementia.

	Crude model			Adjusted model*
	HR	95% CI	p	HR	95% CI	p
Presence of psychological symptoms
No	1.00	(Reference)		1.00	(Reference)
Yes	2.27	1.65–3.12	<0.001	1.48	1.06–2.06	0.021
Covariates
Age				1.17	1.13–1.20	<0.001
Sex				1.58	0.97–2.56	0.066
Education				1.10	0.98–1.13	0.178
Body mass index				0.99	0.94–1.04	0.718
MMSE score				0.94	0.87–1.02	0.142
Grip strength				0.92	0.89–0.95	<0.001
Number of medications				1.14	1.08–1.20	<0.001
Hypertension				0.84	0.60–1.17	0.299
Diabetes				1.09	0.72–1.65	0.693
Hyperlipidemia				0.75	0.53–1.07	0.114
Heart diseases				0.53	0.34–0.84	0.007
Respiratory disease				0.77	0.46–1.29	0.316
Current smoker				1.89	1.01–3.52	0.047
Current alcohol drinker				0.73	0.48–1.10	0.134

HR: hazard ratio; CI: confidence interval.

*Adjusted for age, sex, years of education, body mass index, cognitive function, grip strength, number of medications, medical history, smoking habits, and alcohol consumption.

Risk of dementia according to a combination of somatic and psychological symptoms

Based on a combination of somatic and psychological symptoms at baseline, the groups were classified as normal, n = 1072 (50.8%); somatic symptoms only, n = 598 (28.3%); psychological symptoms only, n = 163 (7.7%); and coexistence groups, n = 278 (13.2%). Table 3 presents the participants’ baseline characteristics. Significant differences were observed among the four groups in terms of age, sex, education, MMSE scores, grip strength, number of medications, presence of hypertension, diabetes, respiratory disease, smoking, and incidence of dementia. During the five-year follow-up period (mean follow-up time in all the participants and normal, somatic and psychological symptoms only, and coexistence groups was 55.4 ± 4.6, 57.0 ± 9.6, 54.0 ± 13.0, 54.8 ± 13.0, and 51.0 ± 16.2 months, respectively), the incidence rates (per 1000 person-years) of dementia in all the participants, normal, somatic and psychological symptoms only, and coexistence groups were 17.0 (95% CI: 14.64–19.84), 10.0 (95% CI: 7.61–13.16), 20.6 (95% CI: 15.86–26.75), 21.5 (95% CI: 13.23–34.91), and 36.4 (95% CI: 27.06–49.08), respectively. Table 4 presents the Cox proportional hazards regression model for the risk of dementia incidence for each group, with the normal group as the reference group. The HR for the incidence of dementia in the somatic (HR 1.42, 95% CI: 0.96–2.09) and psychological symptoms only groups (HR 1.47, 95% CI: 0.83–2.59) were not significantly different from those in the normal group. However, they were higher in the coexistent group than the normal group (HR 1.91, 95% CI: 1.24–2.94).

Table 3.

Participants’ characteristics based on the combination of somatic and psychological symptoms.

	Overall		Normal		Somatic symptoms only		Psychological symptoms only		Coexistence		p
	n = 2111		n = 1072		n = 598		n = 163		n = 278		p
Age, y	73	[68–78]	72	[68–77]	74	[69–79]	74	[69–79]	75	[70–80]	<0.001
Sex, male, n (%)	834	(39.5)	433	(40.4)	208	(34.8)	74	(45.4)	119	(42.8)	0.023
Education, y	11	[9–12]	12	[9–12]	11	[9–12]	10	[9–12]	9	[9–12]	<0.001
Body mass index, kg/m²	23.1	[21.2–31.8]	23.2	[21.4–25.2]	23.3	[21.2–25.8]	22.8	[20.7–25.4]	23.0	[20.7–25.0]	0.064
MMSE score, point	28	[26–28]	28	[26–29]	28	[26–29]	28	[26–29]	27	[26–29]	<0.001
Grip strength, kg	25.1	[21.4–31.8]	26.1	[22.2–32.8]	24.5	[21.1–29.8]	24.7	[20.7–31.8]	23.9	[19.7–28.8]	<0.001
Number of medications	3	[1–4]	2	[1–4]	3	[1–5]	3	[1–5]	3	[1–6]	<0.001
Chronic disease
Hypertension, n (%)	1072	(50.8)	521	(48.6)	330	(55.2)	75	(46.0)	146	(52.5)	0.037
Diabetes, n (%)	307	(14.5)	127	(11.8)	97	(16.2)	25	(15.3)	58	(20.9)	<0.001
Hyperlipidemia, n (%)	695	(32.9)	344	(32.1)	207	(34.6)	58	(35.6)	86	(30.9)	0.545
Heart diseases, n (%)	362	(17.1)	168	(15.7)	112	(18.7)	25	(15.3)	57	(20.5)	0.153
Respiratory disease, n (%)	197	(9.3)	83	(7.7)	57	(9.5)	15	(9.2)	42	(15.1)	0.003
Current smoker, n (%)	173	(8.2)	78	(7.3)	43	(7.2)	16	(9.8)	36	(12.9)	0.012
Current alcohol drinker, n (%)	654	(31.0)	355	(33.1)	168	(28.1)	45	(27.6)	86	(30.9)	0.140
Incident of dementia, n (%)	166	(7.9)	51	(4.8)	56	(9.4)	16	(9.8)	43	(15.5)	<0.001

MMSE: Mini-Mental State Examination.

Data are expressed as n (%) or median [interquartile]. Kruskal–Wallis and χ² tests were conducted for continuous and categorical variables, respectively.

Table 4.

Combination of somatic and psychological symptoms of depression and risk of dementia.

			Crude model			Adjusted model*
	Total number of Participants	Number of cases of dementia/person-years	HR	95% CI	p	HR	95% CI	p
Somatic and psychological symptoms status
Normal	1072	51/5096	Reference			Reference
Somatic symptoms only	598	56/2719	2.08	1.42–3.01	<0.001	1.42	0.96–2.09	0.078
Psychological symptoms only	163	16/745	2.17	1.24–3.80	0.007	1.47	0.83–2.59	0.186
Coexistence	278	43/1180	3.73	2.48–5.59	<0.001	1.91	1.24–2.94	0.003
Covariates
Age						1.17	1.13–1.20	<0.001
Sex						1.57	0.97–2.55	0.067
Education						1.06	0.98–1.14	0.145
Body mass index						0.99	0.94–1.04	0.721
MMSE score						0.94	0.87–1.02	0.160
Grip strength						0.92	0.89–0.96	<0.001
Number of medications						1.13	1.07–1.19	<0.001
Hypertension						0.82	0.59–1.16	0.260
Diabetes						1.09	0.71–1.66	0.687
Hyperlipidemia						0.76	0.53–1.09	0.137
Heart diseases						0.53	0.34–0.84	0.007
Respiratory disease						0.77	0.46–1.30	0.327
Current smoker						1.86	0.10–3.48	0.051
Current alcohol drinker						0.73	0.48–1.10	0.132

HR: hazard ratio; CI: confidence interval.

*Adjusted for age, sex, years of education, body mass index, cognitive function, grip strength, number of medications, medical history, smoking habits, and alcohol consumption.

Discussion

This study examined the relationship between the presence of somatic and psychological symptoms of depressive symptoms and dementia and found that each of these symptoms was associated with risk. Previous studies also reported an association between the somatic and psychological aspects of depressive symptoms and the risk of dementia. Saha et al. reported that greater appetite and weight loss symptoms were associated with a higher risk of dementia in older adults with normal cognitive function who were depressed.¹⁷ Bokenberger et al. and Tsapanou et al. found that sleep problems, which included sleep inadequacy and daytime sleepiness, were associated with an increased risk of dementia.^42,43 Furthermore, Verdelho et al. reported that depressive symptoms predicted the incidence of dementia independent of the changes in cerebral white matter.⁶ Our results revealed that the psychological and somatic symptoms in people with depression were associated with the risk of incidence of dementia, which is consistent with those of previous studies. However, previous studies did not assess somatic and psychological symptoms separately nor examine their combination with the risk of dementia. Older adults diagnosed with major depression have both somatic and psychological symptoms. Older adults with depressive symptoms who have not been diagnosed with depression do not necessarily have both somatic and psychological symptoms. Therefore, it is important to focus on each of these symptoms, even in older adults with depressive symptoms.

Therefore, we assessed somatic and psychological symptoms separately. Furthermore, we examined the association between the somatic and psychological aspects of depressive symptoms and their combination with the incidence of dementia over five years. The incidence of dementia among participants was 17.0 (95% CI: 14.64–19.84) per 1000 person-years. A previous meta-analysis reported that the pooled incidence of dementia was 17.2 (95% CI: 13.9–21.2) among community-dwelling older adults, which was consistent with our results.⁴⁴ Of the participants, 876 (41.5%) had at least one somatic symptom; however, only 278 (31.7%) had some psychological symptoms among them. Older adults with depression reported fewer psychological symptoms and more somatic symptoms than young adults with depression.²¹ Our results represented the characteristics of depression in old age. Overall, 441 participants (20.9%) had psychological symptoms, of which 278 (63.0%) had some somatic symptoms. There were 278 participants (13.2% of the total) who had both somatic and psychological symptoms.

In the Cox proportional hazards regression model that analyzed the relationship between the combination of somatic and psychological symptoms and the incidence of dementia, it was shown that the risk of dementia for participants with either somatic or psychological symptoms was not significantly different from that of healthy participants. However, the coexistence of these symptoms increases the risk of dementia. Geerlings et al. examined whether a history of depressive episodes and the presence of depressive symptoms were associated with an increased risk of AD.⁴⁵ Participants with early-onset depression had an increased risk of AD; however, depressive symptoms at baseline were not associated with an increased AD risk. Considering that major depression was diagnosed when both somatic and psychological symptoms were present simultaneously,⁴⁶ the finding that the coexistence of somatic and psychological symptoms increases the risk of dementia incidence extends the results of previous studies. Almeida et al. examined the association between the severity of depressive symptoms and the risk of dementia. A graded association was observed between the severity of depressive symptoms and the risk of dementia, with severe depression being associated with a higher risk.⁴⁷ As indicated by previous results, participants in the current study who had either somatic or psychological symptoms could have been in the prodromal phase of depression or had depression of low severity. Although some studies have reported that depressive symptoms are associated with the incidence of dementia,^5–7 others have found an association only among older adults with certain characteristics.^45,48 A factor that could contribute to this discrepancy could be the use of different methods to assess depression. Previous studies included some somatic symptoms in their assessment of depressive symptoms; however, as they did not assess psychological symptoms independent from somatic symptoms, they were unable to assess their co-existence. Additionally, other studies only assessed psychological symptoms and did not consider somatic symptoms.^6,48 Our results suggest the importance of assessing the presence of both somatic and psychological symptoms when assessing depression as a risk factor for dementia. We defined somatic symptoms as the presence of one or more of the four commonly found in depression. Future studies should conduct a detailed assessment of each somatic symptom and its association with the risk of incidence of dementia to establish strategies for the prevention of dementia.

Strengths and limitations

A major strength of our study was that we analyzed a large sample using information obtained from the monthly incidence of dementia-tracking data from Japan's health insurance, older adults’ medical care, and long-term care insurance systems. In addition, we used data restricted to older adults with high cognitive function at baseline, adjusted for various confounding factors. Therefore, further reliable results on the association between depressive symptoms and dementia were obtained. However, this study has several limitations. First, the participants included older adults who were invited to participate in the assessment at the community center. Therefore, it was possible that older adults with more severe depressive symptoms did not participate. This selection bias may have led to an underestimation of the incidence of dementia. We also classified participants based on their diagnosis of major depression at baseline to determine a cutoff value for depression in the assessment of somatic symptoms. The low prevalence of major depression (1.2%) was likely affected because of this baseline assessment. Second, a self-report questionnaire was used to assess somatic symptoms, which may have introduced reporting bias. Furthermore, the diagnosis of major depression used to determine the cutoff value for depression in the assessment of somatic symptoms was based on the participant's self-report. In the future, a scale that can comprehensively assess somatic symptoms caused by depression should be developed, and its reliability and validity should also be verified. Third, although this study found a statistically significant association between the coexistence of somatic and psychological symptoms and the incidence of dementia, the hazard ratio in the model adjusted for covariates was 1.91, which was relatively low; consequently, the clinical significance may be limited, and caution should be exercised while interpreting the results. Finally, we discuss the limitations of the study design. Given the efficient use of resources and minimization of selection bias, it would have been preferable to design this study as a nested case-control (NCC) study. However, the sample size was too small to design an NCC study, as 166 participants (7.9% of the total) had an incidence of dementia in our cohort study. In addition, the incidence of dementia in this study was limited to a 5-year follow-up period. A follow-up period of only 5 years may not capture long-term health outcomes and disease progression, which may have led to underestimation of dementia incidence. In the future, the results should be supplemented, and the reliability of the results should be increased by conducting follow-up assessments over a long period with a higher number of participants and by adding severity-based analysis. Despite these limitations, to the best of our knowledge, this study was the first to assess somatic and psychological aspects included in depressive symptoms separately and to examine their combination and risk of incidence of dementia. Our findings highlight the importance of addressing somatic and psychological symptoms before they coexist as a potential strategy to prevent or delay the incidence of dementia.

Conclusion

Our results suggest that each somatic and psychological symptom of depression independently and significantly increases the risk of incidence of dementia. In addition, the coexistence of somatic and psychological symptoms was associated with a higher risk of dementia incidence. We suggest that assessments and countermeasures for somatic and psychological symptoms, respectively, may be important strategies to prevent or delay dementia.

Footnotes

Acknowledgments

We would like to thank the Takahama City office for help with participant recruitment. We would also like to thank all the participants who assisted in the research for this study.

ORCID iD

Yuka Misu

Author contributions

Yuka Misu (Conceptualization; Data curation; Formal analysis; Funding acquisition; Methodology; Visualization; Writing – original draft; Writing – review & editing); Kota Tsutsumimoto (Conceptualization; Data curation; Formal analysis; Methodology; Writing – original draft; Writing – review & editing); Yuto Kiuchi (Formal analysis; Methodology; Visualization; Writing – review & editing); Kazuhei Nishimoto (Data curation; Formal analysis; Methodology; Writing – review & editing); Tomoka Ohata (Validation; Writing – review & editing); Hiroyuki Shimada (Conceptualization; Funding acquisition; Investigation; Methodology; Project administration; Supervision; Writing – review & editing).

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the JSPS KAKENHI Grant-in-Aid for Scientific Research A (26242059), Research Funding for Longevity Sciences from the National Center for Geriatrics and Gerontology (27-22), AMED under Grant Number 15dk0107003h0003, 15dk0207004h0203, Research Project on Health and Welfare Promotion for the Elderly, and Grant-in Aid for Scientific Research Activity start-up (23 K 19915).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability

Datasets used and/or analyzed in this study are available from the corresponding author on reasonable request. The data are not publicly available due to privacy or ethical restrictions.

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