Effect of a home-based, dynamic, multidomain intervention on cognitive function in patients with cardiometabolic multimorbidity and their caregivers: The 'LifeWise' randomized controlled trial protocol.

The prevalence of cardiometabolic morbidity (e.g., high blood pressure, heart attack, stroke, type 2 diabetes) and multimorbidity development (2 or more cardiometabolic morbidities) are rapidly growing in the US. Cardiometabolic morbidity and multimorbidity are linked to poor well-being outcomes, high healthcare costs, and mortality. There is little known about cardiometabolic multimorbidity health disparities, particularly regarding mutable factors that might be targeted in future health interventions. In the present study, using a biopsychosocial framework (Biobehavioral Family Model), we examine whether cardiometabolic morbidity and multimorbidity development are linked to premorbid family and marital relationships and if it differs depending on socioeconomic status (i.e., educational attainment) using three waves of Midlife in the US (N = 4951). We assessed cardiometabolic development with three conceptualizations: number of cardiometabolic morbidities (i.e., count variable), individual cardiometabolic morbidities (i.e., diabetes, high blood pressure, stroke, heart attack), and severity of cardiometabolic multimorbidity (e.g., 3+ vs. zero morbidities). Family strain increased the number of cardiometabolic morbidities (OR = 1.17) and the severity of multimorbidity (e.g., 3+ morbidities: OR = 1.38). People with a high school education experienced family support as a buffer to the negative health impact of education level. Generally, marital quality appeared less impactful on cardiometabolic morbidity and multimorbidity development compared to family strain. Positive and negative family characteristics appear to function differently across educational attainment. These findings indicate that adults' non-intimate family relationships predict important outcomes such as diabetes, heart attack, stroke, and cardiometabolic multimorbidity and should be considered targets for preventative health interventions.

The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol.

Multi-domain interventions for the prevention of dementia and cognitive decline.

<p dir="ltr">Specific cardiometabolic diseases (CMDs) - including type 2 diabetes, heart disease, and stroke - have been individually linked to increased risk of dementia. With population aging, a growing number of older adults are living with cardiometabolic multimorbidity - i.e., the presence of multiple, co-occurring CMDs. However, the role of cardiometabolic multimorbidity in the development of dementia is not well-understood. This thesis aimed to explore the complex interplay between cardiometabolic multimorbidity, cognitive decline, and dementia, and to identify possible compensatory factors that may attenuate the detrimental influence of CMDs on cognitive and brain health. This was carried out using data from three longitudinal studies: the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), the Screening Across the Lifespan Twin (SALT) study, and the UK Biobank (UKB).</p><p dir="ltr">Study I. The relationship between CMDs and cognitive phenotypes in the preclinical/prodromal phase of dementia was examined using 12y follow-up data from SNAC-K (n=2,577). Cardiometabolic multimorbidity was associated with accelerated cognitive decline (ß -0.03 [-0.04, -0.02]) and a significantly increased risk of both cognitive impairment (HR 1.73 [1.23, 2.44]) and its progression to dementia (HR 1.86 [1.17, 2.97]).</p><p dir="ltr">Study II. The association between cardiometabolic multimorbidity and dementia was assessed using 18y follow-up data from 17,913 twin individuals from SALT. Cardiometabolic multimorbidity was associated with a significantly increased risk of all-cause dementia (HR 1.42 [1.31, 1.53), Alzheimer's disease (HR 1.26 [1.10, 1.45]) and vascular dementia (HR 1.64 [1.42, 1.88]). Comparison of monozygotic and dizygotic twin pairs further indicated that genetic factors may underlie the association between CMDs and dementia.</p><p dir="ltr">Study III. Cognitive reserve (characterized by higher educational and occupational attainment, social stimulation, and engagement in leisure activities) was explored as a potential compensatory factor that might attenuate the association between CMDs and dementia using 15y follow-up data from UKB (n=216,178). People with CMDs and moderate-to-high compared to low levels of cognitive reserve had 17% lower risk of dementia (HR 0.83 [0.77, 0.91]) and significantly larger volumes of gray matter and hippocampus on brain MRI.</p><p dir="ltr">Study IV. The compensatory role of anti-inflammatory diet in the CMD-dementia association was examined using 15y follow-up data from UKB (n=84,342). People with CMDs and an anti-inflammatory compared to pro- inflammatory diet had 31% lower risk of dementia (HR 0.69 [0.55, 0.88]) as well as a significantly larger volume of gray matter and significantly smaller volume of white matter hyperintensities on brain MRI.</p><p dir="ltr">Conclusions. Together, the findings highlight cardiometabolic multimorbidity as an especially high-risk state for a continuum of cognitive phenotypes spanning from accelerated cognitive decline to cognitive impairment and dementia. This appears to involve both neurodegenerative and vascular processes in the brain. Further, genetic background may underpin the CMD-dementia association. However, modifiable factors including high levels of cognitive reserve and adherence to an anti-inflammatory diet appear to attenuate the association between CMDs, brain pathologies, and dementia.</p><p dir="ltr">Keywords: Cardiometabolic disease, dementia, Alzheimer's disease, vascular dementia, cognitive decline, brain MRI, cognitive reserve, anti-inflammatory diet, population-based study, twin study</p><h3>List of scientific papers</h3><p dir="ltr">This thesis is based on the following original papers, which will be referred to in the text as Studies I, II, III, and IV.</p><p dir="ltr">I. <b>Dove A,</b> Marseglia A, Shang Y, Vetrano DL, Grande G, Laukka EJ, Fratiglioni L, Xu W. Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression. Alzheimer's & Dementia. 2022 Jun 16; 19(3): 821-830. <br><a href="https://doi.org/10.1002/alz.12708">https://doi.org/10.1002/alz.12708</a><br></p><p dir="ltr"><br></p><p dir="ltr">II. <b>Dove A,</b> Guo J, Marseglia A, Fastbom J, Vetrano DL, Fratiglioni L, Pedersen N, Xu W. Cardiometabolic multimorbidity and incident dementia: the Swedish twin registry. European Heart Journal. 2023 Feb 14; 44(7): 573-582.<br><a href="https://doi.org/10.1093/eurheartj/ehac744">https://doi.org/10.1093/eurheartj/ehac744</a><br></p><p dir="ltr"><br></p><p dir="ltr">III. <b>Dove A,</b> Yang W, Dekhtyar S, Guo J, Wang J, Marseglia A, Vetrano DL, Whitmer RA, Xu W. High cognitive reserve attenuates the risk of dementia associated with cardiometabolic diseases. Alzheimer's Research & <a href="https://doi.org/10.1186/s13195-024-01528-2" rel="noreferrer" target="_blank">https://doi.org/10.1186/s13195-024-01528-2</a><br></p><p dir="ltr"><br></p><p dir="ltr">IV. <b>Dove A,</b> Dunk MM, Wang J, Guo J, Whitmer RA, Xu W. Anti- inflammatory diet and dementia in older adults with cardiometabolic diseases. JAMA Network Open. 2024 Aug 12; 7(8): e2427125. <br><a href="https://doi.org/10.1001/jamanetworkopen.2024.27125">https://doi.org/10.1001/jamanetworkopen.2024.27125</a><br></p><p dir="ltr"><br></p>

<p dir="ltr">Specific cardiometabolic diseases (CMDs) - including type 2 diabetes, heart disease, and stroke - have been individually linked to increased risk of dementia. With population aging, a growing number of older adults are living with cardiometabolic multimorbidity - i.e., the presence of multiple, co-occurring CMDs. However, the role of cardiometabolic multimorbidity in the development of dementia is not well-understood. This thesis aimed to explore the complex interplay between cardiometabolic multimorbidity, cognitive decline, and dementia, and to identify possible compensatory factors that may attenuate the detrimental influence of CMDs on cognitive and brain health. This was carried out using data from three longitudinal studies: the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), the Screening Across the Lifespan Twin (SALT) study, and the UK Biobank (UKB).</p><p dir="ltr">Study I. The relationship between CMDs and cognitive phenotypes in the preclinical/prodromal phase of dementia was examined using 12y follow-up data from SNAC-K (n=2,577). Cardiometabolic multimorbidity was associated with accelerated cognitive decline (ß -0.03 [-0.04, -0.02]) and a significantly increased risk of both cognitive impairment (HR 1.73 [1.23, 2.44]) and its progression to dementia (HR 1.86 [1.17, 2.97]).</p><p dir="ltr">Study II. The association between cardiometabolic multimorbidity and dementia was assessed using 18y follow-up data from 17,913 twin individuals from SALT. Cardiometabolic multimorbidity was associated with a significantly increased risk of all-cause dementia (HR 1.42 [1.31, 1.53), Alzheimer's disease (HR 1.26 [1.10, 1.45]) and vascular dementia (HR 1.64 [1.42, 1.88]). Comparison of monozygotic and dizygotic twin pairs further indicated that genetic factors may underlie the association between CMDs and dementia.</p><p dir="ltr">Study III. Cognitive reserve (characterized by higher educational and occupational attainment, social stimulation, and engagement in leisure activities) was explored as a potential compensatory factor that might attenuate the association between CMDs and dementia using 15y follow-up data from UKB (n=216,178). People with CMDs and moderate-to-high compared to low levels of cognitive reserve had 17% lower risk of dementia (HR 0.83 [0.77, 0.91]) and significantly larger volumes of gray matter and hippocampus on brain MRI.</p><p dir="ltr">Study IV. The compensatory role of anti-inflammatory diet in the CMD-dementia association was examined using 15y follow-up data from UKB (n=84,342). People with CMDs and an anti-inflammatory compared to pro- inflammatory diet had 31% lower risk of dementia (HR 0.69 [0.55, 0.88]) as well as a significantly larger volume of gray matter and significantly smaller volume of white matter hyperintensities on brain MRI.</p><p dir="ltr">Conclusions. Together, the findings highlight cardiometabolic multimorbidity as an especially high-risk state for a continuum of cognitive phenotypes spanning from accelerated cognitive decline to cognitive impairment and dementia. This appears to involve both neurodegenerative and vascular processes in the brain. Further, genetic background may underpin the CMD-dementia association. However, modifiable factors including high levels of cognitive reserve and adherence to an anti-inflammatory diet appear to attenuate the association between CMDs, brain pathologies, and dementia.</p><p dir="ltr">Keywords: Cardiometabolic disease, dementia, Alzheimer's disease, vascular dementia, cognitive decline, brain MRI, cognitive reserve, anti-inflammatory diet, population-based study, twin study</p><h3>List of scientific papers</h3><p dir="ltr">This thesis is based on the following original papers, which will be referred to in the text as Studies I, II, III, and IV.</p><p dir="ltr">I. <b>Dove A,</b> Marseglia A, Shang Y, Vetrano DL, Grande G, Laukka EJ, Fratiglioni L, Xu W. Cardiometabolic multimorbidity accelerates cognitive decline and dementia progression. Alzheimer's & Dementia. 2022 Jun 16; 19(3): 821-830. <br><a href="https://doi.org/10.1002/alz.12708">https://doi.org/10.1002/alz.12708</a><br></p><p dir="ltr"><br></p><p dir="ltr">II. <b>Dove A,</b> Guo J, Marseglia A, Fastbom J, Vetrano DL, Fratiglioni L, Pedersen N, Xu W. Cardiometabolic multimorbidity and incident dementia: the Swedish twin registry. European Heart Journal. 2023 Feb 14; 44(7): 573-582.<br><a href="https://doi.org/10.1093/eurheartj/ehac744">https://doi.org/10.1093/eurheartj/ehac744</a><br></p><p dir="ltr"><br></p><p dir="ltr">III. <b>Dove A,</b> Yang W, Dekhtyar S, Guo J, Wang J, Marseglia A, Vetrano DL, Whitmer RA, Xu W. High cognitive reserve attenuates the risk of dementia associated with cardiometabolic diseases. Alzheimer's Research & <a href="https://doi.org/10.1186/s13195-024-01528-2" rel="noreferrer" target="_blank">https://doi.org/10.1186/s13195-024-01528-2</a><br></p><p dir="ltr"><br></p><p dir="ltr">IV. <b>Dove A,</b> Dunk MM, Wang J, Guo J, Whitmer RA, Xu W. Anti- inflammatory diet and dementia in older adults with cardiometabolic diseases. JAMA Network Open. 2024 Aug 12; 7(8): e2427125. <br><a href="https://doi.org/10.1001/jamanetworkopen.2024.27125">https://doi.org/10.1001/jamanetworkopen.2024.27125</a><br></p><p dir="ltr"><br></p>

Multi-Domain Interventions for Dementia Prevention–A Systematic Review

SummaryBackgroundIndividual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes.MethodsWe examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006–10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics.FindingsThe dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39–9·08, p<0·0001, and 1·68, 1·53–1·84, p<0·0001, respectively). Participants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia (HR 5·74, 95% CI 4·26–7·74, p<0·0001), compared with those with a low genetic risk and no cardiometabolic conditions. Crucially, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume (F2, 12 110 = 10·70; p<0·0001) and total grey matter volume (F2, 12 236 = 55·65; p<0·0001).InterpretationCardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk.FundingWellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.

BACKGROUND Dementia is a worldwide concern. Its global prevalence is increasing. Currently, no effective medical treatment exists to cure or to delay the onset of cognitive decline or dementia. Up to 40% of dementia is attributable to potentially modifiable risk factors, which has led to the notion that targeting these risk factors might reduce the incidence of cognitive decline and dementia. Since sporadic dementia is a multifactorial condition, thought to derive from multiple causes and risk factors, multi-domain interventions may be more effective for the prevention of dementia than those targeting single risk factors. OBJECTIVES To assess the effects of multi-domain interventions for the prevention of cognitive decline and dementia in older adults, including both unselected populations and populations at increased risk of cognitive decline and dementia. SEARCH METHODS We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), and ClinicalTrials.gov on 28 April 2021. We also reviewed citations of reference lists of included studies, landmark papers, and review papers to identify additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA We defined a multi-domain intervention as an intervention with more than one component, pharmacological or non-pharmacological, but not consisting only of two or more drugs with the same therapeutic target. We included randomised controlled trials (RCTs) evaluating the effect of such an intervention on cognitive functioning and/or incident dementia. We accepted as control conditions any sham intervention or usual care, but not single-domain interventions intended to reduce dementia risk. We required studies to have a minimum of 400 participants and an intervention and follow-up duration of at least 12 months. DATA COLLECTION AND ANALYSIS We initially screened search results using a 'crowdsourcing' method in which members of Cochrane's citizen science platform identify RCTs. We screened the identified citations against inclusion criteria by two review authors working independently. At least two review authors also independently extracted data, assessed the risk of bias and applied the GRADE approach to assess the certainty of evidence. We defined high-certainty reviews as trials with a low risk of bias across all domains other than blinding of participants and personnel involved in administering the intervention (because lifestyle interventions are difficult to blind). Critical outcomes were incident dementia, incident mild cognitive impairment (MCI), cognitive decline measured with any validated measure, and mortality. Important outcomes included adverse events (e.g. cardiovascular events), quality of life, and activities of daily living (ADL). Where appropriate, we synthesised data in random-effects meta-analyses. We expressed treatment effects as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS We included nine RCTs (18.452 participants) in this review. Two studies reported incident dementia as an outcome; all nine studies reported a measure for cognitive functioning. Assessment of cognitive functioning was very heterogeneous across studies, ranging from complete neuropsychological assessments to short screening tests such as the mini-mental state examination (MMSE). The duration of the interventions varied from 12 months to 10 years. We compared multi-domain interventions against usual care or a sham intervention. Positive MDs and RRs 6 points (MD 0.07, 95%CI -0.00 to 0.15). AUTHORS' CONCLUSIONS We found no evidence that multi-domain interventions can prevent incident dementia based on two trials. There was a small improvement in cognitive function assessed by a NTB in the group of participants receiving a multi-domain intervention, although this effect was strongest in trials offering cognitive training within the multi-domain intervention, making it difficult to rule out a potential learning effect. Interventions were diverse in terms of their components and intensity.

It is unknown in which, if any, subgroups of older adults multidomain interventions are effective at reducing long-term dementia incidence. We pooled up to 12 years of follow-up data from 5205 participants aged > 70 from the Multidomain Alzheimer Preventive Trial (MAPT) and Prevention of Dementia by Intensive Vascular Care (preDIVA) studies. The primary outcome was incident all-cause dementia. Pre-specified subgroups were defined by dementia risk factors (age, sex, education, apolipoprotein E [APOE] genotype, cognitive status, and cardiovascular risk factors). Four hundred eighty-six participants developed dementia during 37,782 person-years of follow-up. Higher incidence was associated with baseline age, APOE ε4 genotype, physical inactivity, Mini-Mental State Examination, and blood pressure. Multidomain intervention had no effect on incident dementia overall (hazard ratio =0.98, 95% confidence interval 0.80-1.21), or in any pre-specified subgroup. A recursive partitioning algorithm also did not detect any subgroups, defined by single or multiple risk factors, showing a differential intervention effect. We did not identify any subgroups of older adults in whom multidomain interventions significantly reduced incident dementia. MAPT: NCT00672685 (clinicaltrials.gov); PreDIVA: ISRCTN29711771 (ISRCTN registry) HIGHLIGHTS: We pooled up to 12 years of follow-up data from two multidomain prevention trials. Five thousand two hundred five participants aged ≥ 70 were included. Subgroups were pre-defined by modifiable and non-modifiable dementia risk factors. A data-driven recursive partitioning algorithm was also used. Multidomain intervention did not lower incident dementia overall or in any subgroup.

It is unknown how greenness affects the development, progression and prognosis of cardiometabolic multimorbidity (CMM). We aimed to evaluate the role of greenness on trajectories of CMM, particularly the transitions from healthy to first cardiometabolic disease (FCMD), then to CMM and followed by death. We used Normalized difference vegetation index (NDVI) as the exposure indicator. CMM was defined as the presence of more than one cardiometabolic diseases, namely ischemic heart disease, type 2 diabetes, and stroke. As a result, among 454,777 participants, 5889 FCMD cases, 6607 CMM cases, and 25,666 death events were observed after a median follow-up of 12.1 years. We found greenness significantly associated with transitions from baseline to FCMD, baseline to death, FCMD to CMM, as well as FCMD to death. When further specifying FCMDs, the effect varied across disease-specific transitions. In conclusion, residential greenness may have an impact on the occurrence, progression and prognosis of CMM.

Exercise has positive impacts on cardiometabolic health. However, evidence regarding the effectiveness of tele-exercise training on cardiorespiratory fitness and heart rate recovery in patients with cardiometabolic multimorbidity remains limited. The aim of this study was to assess whether an assumed increase in physical activity (PA) after a 12-week tele-exercise training program improved cardiorespiratory fitness and heart rate recovery of patients with cardiometabolic multimorbidity. A parallel-group randomized controlled trial was conducted. Eligible patients with cardiometabolic multimorbidity (n=83) were randomized 1:1 to either an experimental group (EG, received a 12-week tele-exercise training program with 3 sessions/week and 30 min/session and weekly remote monitoring for maintenance of exercise) or a control group (CG, usual care only). PA, cardiorespiratory fitness, and heart rate recovery were assessed at baseline and 12 weeks. Generalized estimating equations were used to examine the intervention effects via the interaction of time and group. Sixty-eight participants (81.9%) completed the study, and 83 were included in the intention-to-treat analysis. The EG with higher vigorous-intensity PA (β=714, p=.037), walking behavior (β=750, p=.0007), and total amount of PA (β=1748, p=.001) after the intervention had significantly elevated cardiorespiratory fitness, including VO2peak (β=3.9, p=.042), workload (β=17.9, p=.034), and anaerobic threshold (β=2.1, p=.041), and increased one-min heart rate recovery (β=5.3, p=.025), compared with the CG. A 12-week tele-exercise training program was effective for increased PA, elevated cardiorespiratory fitness, and improved heart rate recovery for patients with cardiometabolic multimorbidity. These findings highlight the feasibility of better delivering lifestyle interventions for cardiometabolic health management.

Multimorbidity and risk of dementia: A systematic review and meta-analysis of longitudinal cohort studies

This study examined the relationship between sleep disorders and the risk of dementia in patients with newly diagnosed type 2 diabetes. This study used the Korean Health Screening Cohort data and included 39 135 subjects aged ≥40 years with new-onset type 2 diabetes between 2004 and 2007, with follow-up throughout 2013. Sleep disorders were measured by F51(sleep disorders not due to a substance or known physiological condition) or G47(sleep disorders) under International Classification of Diseases, Tenth Revision (ICD-10) codes as a primary diagnosis, and the adjusted hazard ratio (AHR) and 95% CI of all-cause dementia, Alzheimer disease, vascular dementia, and other dementia were estimated using multivariable Cox proportional hazards regression models. In the patients with type 2 diabetes with an age range between 42 and 84 years (M = 57.8, SD = 9.5), this study identified 2059 events of dementia during an average follow-up time of 5.7 years. In patients with type 2 diabetes, subjects with sleep disorders were associated with an increased risk of all-cause dementia (AHR, 1.46; 95% CI, 1.19-1.80), Alzheimer disease (AHR, 1.39; 95% CI, 1.02-1.88), and other dementia (AHR, 1.69; 95% CI, 1.23-2.31) compared to those without sleep disorders. Men (AHR, 1.93; 95% CI, 1.42-2.62) and older adults (AHR, 1.70; 95% CI, 1.35-2.15) with sleep disorders were associated with an increased risk of dementia than their counterparts without sleep disorders among patients with type 2 diabetes. These findings suggest that sleep disorders are significantly associated with an increased risk of dementia in patients with new-onset type 2 diabetes.

Inequalities in residential green space and trajectory of cardiometabolic multimorbidity: Different associations by sex and socioeconomic status.

Mild cognitive impairment (MCI) increases the risk of dementia. Reducing modifiable lifestyle-related risk factors can help prevent cognitive decline in patients with MCI. We examined whether a multidomain intervention using a mobile application can prevent cognitive decline in patients with MCI. The trial is designed in accordance with the CONSORT Statement. We conducted an assessor-blind, randomized controlled trial. Patients with MCI, aged over 60 years and presenting with at least one modifiable risk factor for dementia, were recruited from three dementia centers in Gangwon-do, Korea, and outpatient clinics at Chuncheon Sacred Heart Hospital. Participants were randomly assigned to either the intervention group or the control group in a 1:1 ratio. Each participant received a 52-week intervention. The intervention group used a mobile application to manage their diet and physical activity at least three times per week, while the control group received general dietary and physical activity recommendations twice a year. The primary outcome was the change in cognitive function measured based on the mini-mental state examination in the Korean version of the CERAD assessment packet (MMSE-KC) score. Between October 2020 and September 2021, 84 people were screened, and 80 participants were randomly assigned to either the control or intervention group (intervention group = 42, control group = 38). Participants in both groups underwent a post-baseline assessment and their data were included in the analysis. We found a positive effect of the multidomain intervention using a mobile application on the change in cognitive function score in the intervention group compared to the control group at the 52-week follow-up. The MMSE-KC (F = 10.6, p < .001) and modified Boston Naming test (F = 8.3, p < .01) scores were significantly higher in the intervention group than in the control group. The results suggest that a multidomain mobile application intervention could help improve cognition in patients with MCI.The study protocol was prospectively registered with the Clinical Research Information Service (CRIS, Republic of Korea; KCT0008315) on March 16, 2023. The full trial details can be accessed at https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22920.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-24865-0.