A Systematic Review and Meta-analysis of the Global Prevalence of Depression in Older Adults with Multi-morbidity

Abstract

Purpose of the Review:

Multi-morbidity, the coexistence of two or more chronic illnesses, is also increasing among older adults in the ageing world. The estimated prevalence of depression is 21.14% in persons with multi-morbidity compared to 3.91% in those without any chronic illness. As there was no data particularly for older adults with multi-morbidity, it was decided to conduct a systematic review of rates of depression.

Collection and Analysis of Data:

This PROSPERO-registered study adhered to PRISMA guidelines. Searches for cross-sectional and population-based studies in the previous ten-year period (2014–2023) in databases and search engines, namely PubMed, Ovid MEDLINE, and PsycINFO, were conducted. Results: From an initial pool of 555 papers, 15 moderate-to-high quality studies were included for the systematic review, of which 10 were eligible for meta-analysis. The pooled prevalence of depression was 46.7% (95% CI = 33.8%–57.4%) for six studies with individuals aged 60 years and above and 12.9% (95% CI = 5.7%–51.5%) for four studies focusing on those aged 65 years or above. Due to variations in defining the age cut-off of 60 and 65 years for older adults, separate analyses were performed.

Conclusions:

Findings reveal that nearly half of older adults with multi-morbidity experience depression. This highlights the importance of the timely detection of depression in general hospitals and primary care settings.

Keywords

Depression multi-morbidity elderly geriatric psychiatry chronic illness

Demographic ageing is driving an epidemiological transition worldwide. Multi-morbidity is typically defined as the presence of two or more chronic conditions in a single individual, without reference to an index condition.¹ Many countries are in the middle of rapid demographic change. Thus, they are witnessing a sudden increase in the number of older people with multi-morbidity who need health and social care.² In coping with that, the healthcare delivery systems in most countries are not yet ready to meet the growing demand for services.³ This can be particularly challenging for the resource-strapped public-run services of low and middle-income countries, both presently and in the coming decades. Estimates of multi-morbidity will help us design cost-effective strategies to address emerging public health challenges like this.

Depressive symptoms and depressive episodes are more frequent in the later years of life. Late-life depression usually has features of atypical depression, somatic complaints out of proportion to medical illness, and sometimes subsyndromal symptoms falling short of meeting diagnostic criteria.⁴ The occurrence of a major depressive episode can negatively impact the outcomes of other co-existing medical problems of the older person. Depression can have a bidirectional relationship with multi-morbidity.⁵ Depression can also be associated with the worsening of multi-morbidity.⁶ Depression is two to three times more likely in people with multi-morbidity compared to people without multi-morbidity or those who have no chronic physical condition.⁷ The presence of depression as part of multi-morbidity demands a more careful approach to clinical management. Depression is also an eminently treatable condition, and health care providers can be trained to identify and manage depression in primary care settings. Early identification and management of depression can help to improve the outcome of other co-existing health conditions.

The estimated prevalence of depression is 21.14% in persons with multi-morbidity compared to 3.91% in those without any chronic illness. Still, this study has not examined older adults in particular.⁷ An estimate of the prevalence of depression among older people with multi-morbidity will enable us to decide on strategies to optimise the management of multi-morbidity in primary care. We wanted to estimate the prevalence of depression among older people with multi-morbidity, as this information is key to the development of multi-component interventions for the health and social care of older people. The study aimed to see if the studies that estimated the magnitude of multi-morbidity among older people in the previous 10 years give reliable information about the prevalence of depression among older people with multi-morbidity.

Methods

The review was done in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020.⁸ The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews in March 2024 under CRD42024519429 before undertaking the review work, particularly the search.

Eligibility Criteria

The types of studies included are cross-sectional, prevalence, and population-based epidemiological studies, which provide prevalence data. Publication in English was one of the inclusion criteria, as the vast majority of papers are published in English, and authors were unsure of the credibility of translations into non-English languages. The review focused on studies involving human participants with multi-morbidity aged 60 years or older. Multi-morbidity in this review refers to the presence of two or more chronic conditions, such as Diabetes, Hypertension, and osteoarthritis.

Study designs, such as Longitudinal, cohort, and survey studies, in which data on the prevalence of depression were unavailable, were excluded. The study population, other than multi-morbid older adults, was excluded from the study before it began. Studies lacking clarity regarding multi-morbidity were also excluded.

Study Selection

The databases and search engines, namely PubMed, Ovid MEDLINE, and PsycINFO, were used for the search. Grey literature, namely BASE, was also searched. A citation search was conducted from the included studies, and all relevant articles were included according to the eligibility criteria.

The search strategy included words or terms ‘depression’, ‘depressive disorder’, ‘multi-morbid’, ‘multi-morbidity’, ‘elderly’, ‘aged’, ‘older people’, ‘prevalence’, ‘cross-sectional studies’, ‘epidemiology’, and relevant others in the English language and humans as in 10 years between 2014 and 2023 were searched. Reviewers decided to study prevalence based only on the most recent research studies, and hence, 10 years was considered reasonable given the available sources at the time of preparing the protocol. The search was mainly done using ti, ab, and MeSH terms when available. The search style adhered to each database’s style. For example, terms were searched using the thesaurus in the PsycINFO database (more details in the supplementary material).

Following the final search, the files in the ‘RIS’ or ‘PubMed’ format, containing article details such as titles and abstracts, were downloaded and added to the COVIDENCE software. Three authors worked on the screening and eligibility assessment stages. Studies were selected independently by two authors (AP and NKH): initially by screening titles and abstracts, and then by full-text screening based on explicit eligibility criteria. The discrepancies between the two authors were resolved by a third author (VH) in both steps; the reference lists of the final included studies were hand-searched for additional studies.

Data Extraction

A Microsoft Excel data collection sheet, comprising the study title, author name, year, country, and continent where the study was conducted, as well as the total population studied and the prevalence (in percentage) of depression among multi-morbid older adults, was compiled. The above data were retrieved by two authors independently (AP and NKH). In the studies in which prevalence rates were not provided directly, calculations were made if relevant data were available, from the proportion of people with depression in multi-morbid elderly participants. The studies were also grouped by continent, using the countries to facilitate data analysis. Tools to assess depression in older people, such as the Geriatric Depression Scale (GDS), the Centre for Epidemiologic Studies for Depression Scale (CES-D), or similar, were considered in the study.

Quality Assessment

Quality assessment of all included studies was performed using the modified Downs and Black, which is relevant for non-randomised controlled studies.⁹ This tool was developed by Sara H Downs and Nick Black in 1998 and is based on epidemiological principles, reviews, and existing checklists, mainly used now for non-randomised studies. The original tool has 26 items, divided into five subscales—reporting, external validity, bias, confounding, and power—with a maximum score of 31. For this study, we used the modified Downs and Black tool, with items related to non-RCTs and those relevant only to prevalence-type studies, which has a maximum score of 10. This tool includes a score of 5 for reporting, 2 each for internal and external validity. The internal consistency and the test-retest reliability of the quality index are high. The inter-rater reliability is good, the quality index score is high, and raters spend approximately 10–20 minutes rating each study. As this review aimed to determine the prevalence, the items were grouped into three main subgroups: reporting, external validity, and internal validity. Quality assessment was done independently by two authors (AP and NKH), and discrepancies were resolved by the third author (VH). A Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment was conducted to determine the certainty of the evidence for the meta-analyses.

Statistical Analyses

COVIDENCE software, Microsoft Excel, and Stata 11.0 were used for study selection, exclusions, analyses, data synthesis, and the creation of forest plots. Effect sizes were prevalence rates with their 95% CI. The sample size in the study helped calculate the effect size. Heterogeneity was assessed by the I² statistic. Studies of a similar design, with available data and the same outcome, were included in meta-analyses. The depression prevalence rates, which were expressed as ratios, were transformed using the Freeman-Turkey transformation to facilitate the meta-analysis and obtain a reliable pooled summary estimate. Then, the results were reversed using the antilog transformation to interpret both individual and pooled summary estimates. Since there are two sets of studies with samples aged 60 years or over, and other studies with samples aged 65 years or over, separate analyses were required for each set. This variation in age is due to different countries adopting 60 or 65 as the age cut-offs for older adults or for geriatric speciality services in general. As anticipated, there were variations across studies; a meta-analysis was conducted using the random-effects model. A p < .05 was considered significant. As part of the subgroup analyses, the analysis was carried out by dividing studies by continent.

Results

Study Selection

A total of 555 studies were screened based on their titles and abstracts, of which 23 were assessed for eligibility. A citation search found one relevant study. Eight studies were ineligible. Finally, 15 studies were included in the systematic review, of which only 10 had the data required for meta-analysis. Refer to Figure 1 for study selection and details about exclusion in Supplementary Material 1 and Table 1.

Figure 1.

PRISMA Flowchart.

Table 1.

Characteristics of Included Studies (N = 15).

Author Year	Age	Gender (%)	Depression Scale Used	Multi-morbid (N)	Depression (n)	Country	Continent	Depression Prevalence
Schwarzbach 2014	65 and more; 74.4 yrs (±5.2)	Female (59.4%) Male (40.6%)	Geriatric Depression Scale-15	3,177	400	Germany	Europe	12.6%
Holvast 2017	60 and more^*		No scale used	760	***	Netherland	Europe	****
DiNapoli 2017^$	50 and more*	**	Not mentioned	34,786	1,367	USA	North America	3.9%
Amaral 2018	60 and 102*	Female (64.6%) Male (35.4%)	Geriatric Depression Scale-15	175	58	Brazil	South America	33.1%
Camargo-Casas 2018	60 and above	**	15-item Geriatric Depression Scale	1,194	386	Colombia	South America	32.32%
Sheridan 2019	50 and above*	**	#	##	***	20 European countries and Israel	Europe and Israel	****
You 2019	60 and above*	**	Geriatric Depression Scale-15	2,201	631	China	Asia	50.7%
Iovino 2020	65 and above	Female (57.4%) Male (42.6%)	PHQ-9	366	240	Italy	Europe	65.7%
Marmamula^$ 2021	60 and above	**	Patient Health Questionnaire (PHQ-9)	50	30	India	Asia	60.0%
Tong 2021^{^}	20 and above No data (n) available for 65 and above	**	Patient Health Questionnaire (PHQ-9)	–	–	USA	North America	****
Zhang 2022^$$	65 and above	Female (58.6%) Male (41.4%)	10-item Centre for Epidemiologic Studies Depression scale (CES-D-10)	Weighted N = 2,245,148	386,166 (calculated from the prevalence)	Canada	North America	17.2%
Smith 2022^@@	65 and above	Female (58.5%) Male (41.5%)	20-item Centre for Epidemiologic Studies Depression (CES-D)	2,373	257	Ireland	Europe	10.8%
Ansari 2022^@	60 and above	Female (54.7%) Male (45.3%)	10-item Centre for Epidemiological Studies Depression Scale (CES-D-10)	7,521 (Female = 4,115, Male = 3406)	2,490	India	Asia	33.1% Female (34.5%) Male (31.2%)
Li 2022^{02537176251403605}	60 and above	**	30-item Geriatric Depression Scale (GDS-30)	1,211	789	Shanghai, China	Asia	65.2%
Botoseneanu 2023^{^^}	65 and above	**	8-item Centre for Epidemiologic Studies Depression (CES-D) scale	8,422	The number of depression cases among somatically multimorbid elderly is not available	USA	North America	****

^*Age does not cater to multi-morbid individuals only.

^**Gender proportion not specified for multi-morbid individual.

^#Scale not specified.

^##The article does not clearly mention the number of multi-morbid individuals.

^***The article does not mention the number of multi-morbid individuals with depression.

^***The article does not specify the prevalence of depression among multi-morbid older people.

^@LASI study-India-Longitudinal Ageing Study in India (LASI).

^$Dual Sensory Impairment (DSI)-Hearing and Visual impairment only. No other morbidities (elderly living in residential homes in Hyderabad, India). Of 867 elderly individuals, only 50 had DSI. Among them, 30 had depression.

^@@The Irish Longitudinal Study on Ageing (TILDA) survey.

^$$Canadian Longitudinal Study of Ageing (CLSA). Multi-morbidity was defined as having three or more chronic conditions. Canada-wide population-based prospective cohort study.

^{^}The National Health and Nutrition Examination Survey (NHANES) Data.

^{02537176251403605}Covered by Shanghai long-term care insurance.

^{^^}Longitudinal data from the Health and Retirement Study (HRS).

HRS is a nationally representative cohort study of noninstitutionalised middle- and older-aged adults. Specific prevalence of depression among somatic multi-morbid older adults is not available.

Fifteen studies were finally found suitable for systematic review. Among them, four were from Europe, four from North America, two from South America, four from Asia, and one spanning 20 European countries and Israel. Of the four European studies, three included elderly individuals aged 65 years and above, and one included those aged 60 years and above. The prevalence of depression among the elderly varied from 10.8% (Ireland) to 12.6% (Germany). However, it was 65.7% in a study from Italy.^10–13 One of the studies from the Netherlands reported multi-morbidity among the depressed elderly, but not the other way around.¹³ Among the four studies from North America, only two studies reported the prevalence of depression among multi-morbid individuals, and it varied from 3.9% (among those 50 years and above) to 17.2% (among those aged 65 years and above).^14–17 All four studies from Asia included the elderly aged 60 years and above, and prevalence ranged from 33.1% (India) to 65.2% (China).^18–21 Two studies from South America reported a similar prevalence of around 33% among the elderly aged 60 and above.^22,23 Longitudinal Ageing study of India data depicts that the prevalence of depression in both males (31.2%) and females (34.5%) has been above 30% suggesting every one in three with multi-morbidity has depression.

The GDS scale, short version (15 Items), was used by four studies, and the GDS (30 Items) by one study. Three studies utilised the Patient Health Questionnaire-9 (PHQ-9), and four studies utilised the CES-D (10-item, 2; 20-item, 1; 8-item, 1). Three studies did not report using any validated scales to assess depression. Hence, these studies were excluded from the forest plot.

From the included studies, it can be noted that prevalence has been increasing in the Asian continent, whereas it has declined in the European and North American populations in recent years.

Risk of Bias Assessment

A checklist of the modified Downs and Black was used to assess the risk of bias. For each selected individual study, external and internal validity were recorded (Table 2), and quality ratios were estimated. Four studies had a ratio of 1, depicting no risk of bias, whereas the least estimated ratio was 0.70. Three studies with a quality score of 0.80 and one study with a quality score of 0.70 were considered of moderate quality.

Table 2.

Quality Assessment of the Included Studies (N = 15).

Author Year	Reporting	External Validity	Internal Validity	Total Score	Ratio
Schwarzbach 2014	6	2	2	10	1.00
DiNapoli 2017	6	1	2	9	0.90
Holvast 2017	6	0	2	8	0.80
Amaral 2018	5	2	2	9	0.90
Camargo-casas S, 2018	5	0	2	7	0.70
Sheridan 2019	5	2	2	9	0.90
You 2019	6	0	2	8	0.80
Iovino 2020	6	0	2	8	0.80
Marmamula 2021	5	2	2	9	0.90
Tong 2021	6	2	2	10	1.00
Ansari 2022	5	2	2	9	0.90
Li 2022	6	2	2	10	1.00
Smith 2022	6	1	2	9	0.90
Zhang 2022	6	1	2	9	0.90
Botoseneanu 2023	6	2	2	10	1.00

Reference: Downs and Black.⁹

Meta-analysis

Of the 15 studies, only 10 papers had the data required for meta-analysis (three studies from North America and two studies from Europe did not provide the necessary data for MA).^{13–15, 24} Of the 10 research papers, six described depression among multi-morbid elderly aged 60 and above,^18–23 and the other four were described among elderly aged 65 and above.^10–12,16 Hence, a meta-analysis was done for the 60+ and 65+ age groups with a pooled estimate for each age group and a combined overall estimate.

From the 10 studies included in the meta-analysis, the total number of multi-morbid elderly persons with depression was 4384 (4384/10,517) and 3,87,063 (3,87,063/22,51,064) in ages 60 years and above and 65 years and above, respectively. The pooled prevalence rate for age 60 years and above was 46.7% (95% CI = 33.8%–57.4%) across six studies, and for age 65 years and above was 12.9% (95% CI = 5.7%–51.5%) across four studies. The overall prevalence of both groups combined was 30.6% (95% CI = 23.8%–51.0%) (Figure 2 and Supplementary Table 2).

Figure 2.

Forest Plot of Depression (Freeman–Tukey Transformation to Depression Prevalence Data) Among Multi-morbid Elderly Aged 60 and 65+ Years.

In the figure, the blue box represents point estimate of each included study, with lines extending being confidence interval, red diamond represents pooled estimate of the included studies, green diamond represents overall pooled estimate.

Subgroup Analysis: Continent-wise Analysis

The pooled prevalence estimated from four studies in Asia was 52.0% (95% CI = 38.0%–66.0%). The pooled prevalence estimated from two studies in South America was 32.4% (95% CI = 30.1%–34.2%). The pooled prevalence estimated from three European studies was 28.0% (95% CI = 3%–65%). There was only one eligible study from North America, which reported a prevalence of 17.20% (95%CI = 15.2%–18.9%) (Figure 3 and Supplementary Table 3).

Figure 3.

Forest Plot of Depression (Freeman–Tukey Transformation to Depression Prevalence Data) Among Multi-morbid Elderly by Region.

In the figure, blue box represents point estimate of each included study, with lines extending being confidence interval, red diamond represents pooled estimate of included studies, green diamond represents overall pooled estimate.

Sensitivity Analysis

According to the quality assessment using the Downs and Black checklist, all studies had a ratio of 0.7 or higher; however, sensitivity analysis was not performed.

Heterogeneity

The I² (%) was 99.58% and 99.78% for the studies included in the meta-analysis of 60+ and 65+ age groups, respectively, indicating considerable heterogeneity among the selected studies. Reasons could include variations in sample size, recruitment, types of morbidity, and study design (Figures 2 and 3).

GRADE: Certainty of Evidence

Certainty of evidence was undertaken using the GRADE approach for overall pooled estimates. Data required for domains such as magnitude of effect, plausible confounding, and dose-response relationships, which are typically relevant to cohort-type studies, were not available. The details are provided in Table S1 (supplementary material). Overall, the evidence assessment yielded moderate certainty in this review, as determined using GRADEpro.²⁵

Publication Bias

Assessment was performed using the Doi plot of the 10 studies included in the meta-analysis. At the start of the review, attempts were made to search both the unpublished and grey literature, which provided a comprehensive search strategy. The Luis Furuya-Kanamori Index value is 0.78, indicating no asymmetry in the Doi plot as in Figure 4. This suggests that meta-analysis is likely free of publication bias and small-study effects.

Figure 4.

LFK = 0.78 indicates there is no asymmetry in the Doi plot within ±1, it is negligible.

Discussion

The pooled prevalence of depression among multi-morbid older people aged 60 years and above was 46.7% (95% CI = 33.8%–57.4%). This systematic review and meta-analysis seem to be the first to address the prevalence of depression among multi-morbid older people. Another systematic review and meta-analysis done earlier has estimated the pooled prevalence of depression among multi-morbid individuals. However, that systematic review and meta-analysis included not only older people but also all adults aged 15 years or older. They reported the prevalence of depression to be 21.14% among those with multi-morbidity.²⁶

Mediation analysis of the data extracted from a baseline survey of the Longitudinal Ageing Survey of India among 31,464 older people above 60 years highlighted the prevalence of depression among multi-morbid older people to be 33.1%. In this study, depression was assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D10).¹⁸ The longitudinal International Mobility Ageing Study (IMIAS) collected information from older people in the age range between 65 years and 74 years from Canada, Brazil, Colombia, and Albania. The study reported the prevalence of depression among multi-morbid older people to be 6.5% in Canada, 8.9% in Latin America, and 19.1% in Albania. Depression was assessed using the CES-D scale.²⁷ During the systematic review, we found only four studies that reported the prevalence of depression in multi-morbid older people aged 65 years and above. The pooled prevalence of depression in multi-morbid older people aged 65 years or more was 12.9% (95% CI = 5.7%–51.5%). The small number of reviewed studies limits the generalizability of this finding to that age group.

The presence of multiple chronic diseases in the same individual is associated with a higher prevalence of depression. Depression itself can lead to the development of cardio-metabolic disorders later. This observation suggests a bidirectional relationship between multi-morbidity and depression, which can be attributed to biological, psychosocial, and care-related factors. Both depression and other health conditions that cause multi-morbidity are considered to be chronic diseases characterised by a high inflammatory burden. Psychosocial factors like lower socio-economic status are associated with high co-occurrence of multi-morbidity and depression. Psychosocial stress, especially the presence of stressful life events, has been linked to both multi-morbidity and depression, which may be attributed to prolonged stress on the hypothalamus-pituitary-adrenal axis. The care-related factors are polypharmacy and the complexities involved in the clinical management of patients with multi-morbidity and depression.^28,29

Our findings point towards the need to carry out a screening for depression and multi-morbidity at primary, secondary, and tertiary levels to optimise the care of older people seeking help in clinical settings. In primary care and secondary care settings, non-specialist healthcare providers like frontline workers can be trained to screen for depression using a simple, easy-to-administer screening tool. They can also assess the presence of multi-morbidity using a checklist for chronic conditions. All older people screened positive for depression can then be seen by a medical officer, who can diagnose and manage depression in primary or secondary care settings or refer them to a specialist care provider in the tertiary care hospital. In the tertiary care hospital, clinicians can clinically evaluate all older people with multi-morbidity for the presence of depression. The older person may need a referral to a geriatrician or psychiatrist if clinical features are suggestive of major depressive disorder or if there is an inadequate response to clinical management of depression by the non-specialist clinician.

Cross-sectional studies have limitations in elucidating the reasons for the higher prevalence of depression in older people. Longitudinal studies can be considered to assess the association between multi-morbidity and depression among older people. Such studies may include measuring biological markers, such as inflammatory markers, at baseline and at follow-up points and endpoints for both exposed and non-exposed cohorts. Such studies are needed for elucidation of the underlying mechanisms for the observed association between multi-morbidity and depression among older people.

Strengths and Limitations of the Study

This seems to be the first study to estimate the pooled prevalence of depression among multi-morbid older people aged 60 years or more. We only looked at recent studies, and the pooled prevalence rate of depression among older people aged 65 or older was based on four studies only. As researchers wanted to examine prevalence in recent studies, excluding older studies might have missed earlier research, thereby influencing the overall understanding of trends.

Conclusions

This meta-analysis aimed to estimate the pooled prevalence of depression among multi-morbid older people. This meta-analysis indicated a high prevalence of depression among multi-morbid older people aged 60 years or more. It also stated the pooled prevalence of depression among multi-morbid older people in different world regions.

Identification of multi-morbidity, as well as the presence of depression, appears to be essential for improving the outcome. Healthcare professionals can assess both depression and multi-morbidity using screening tools and checklists. This will enable timely management by a trained clinician or referral of cases of depression to a specialist mental health care provider. Early identification and prompt interventions can help to mitigate the severity of depression as well as its negative impact on multi-morbidity.

Supplemental Material

Supplemental material for this article available online.

Supplemental Material

Supplemental material for this article available online.

Footnotes

Declaration of Conflicting Interests

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

Declaration Regarding the Use of Generative AI

None used.

Ethical Approval

Not applicable as this is a registered Systematic Review that followed PRISMA guidelines.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

Patient Consent

Not applicable.

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