Wang K, Zhao S, Lee EK, Yau SZ, Wu Y, Hung CT, Yeoh EK.
Risk of Dementia Among Patients With Diabetes in a Multidisciplinary, Primary Care Management Program.
JAMA Netw Open. 2024 Feb 5;7(2):e2355733.
PubMed.
Wang and colleagues' interesting study showed that a multidisciplinary diabetes management program in primary care settings was associated with a reduced risk of dementia incidence among patients with T2D in a cohort study in Hong Kong. Patients with T2D who attended the Risk Assessment and Management Program-Diabetes Mellitus (RAMP-DM), had a 28 percent lower risk of all-cause dementia incidence compared with patients who did not attend the program and received only usual care. A significant risk reduction was seen also for dementia subtypes; Alzheimer’s disease, vascular dementia, and other or unspecified dementia (based on EHR data). A moderate glycaemic control target of HbA1C between 6.5 and 7.5 percent was associated with lower dementia incidence.
A surprising finding is that the dementia risk started to differ between groups immediately after the study onset. The authors conclude that “patients in the RAMP-DM group were still likely to have greater health consciousness than those in the usual care group, which may have led to differences in dementia incidence” and these could at least partially explain the results. On the other hand, it is also likely that clinical evaluation of patients in the RAMP-DM group, including cognitive assessment, was more comprehensive than in the usual care group leading to a more sensitive dementia diagnosis in the RAMP-DM group. Given all this, it is interesting that the study could still find significant differences between the two groups.
Although retrospective, this is a large study (55,618 participants) with a long follow-up (eight years), making its finding relevant and promising. It is challenging to study dementia incidence in randomized controlled trial (RCT) settings. This study clearly reinforces the link between T2D and dementia and its subtypes, and indicates that appropriate management has substantial long-term benefits also on the prevention and risk reduction of dementia.
Importantly, this study supports the ever-increasing body of evidence that dementia prevention/risk reduction interventions are most likely to succeed when they are multimodal, i.e., addressing multiple risk factors and mechanisms at the same time, multidisciplinary, tailored to the patient, sustainable, and sufficiently intensive (Stephen et al., 2021). In this study, RAMP-DM assessment was repeated continuously once every one to three years based on estimated risk level, and the patients were referred to a specialist for related diabetic complications. This risk-stratification process and multidisciplinary coordination enabled more individualized programs and can be one of the key factors behind the positive and strong findings.
The mean age at the time of dementia diagnosis was around 82 years, thus the study highlights the importance of adequate diabetes management even later in life. More work is needed to determine optimal glycaemic control targets (which may differ across age groups).
In general, in terms of identifying the most effective dementia risk reduction strategies for different at-risk populations, we are still in relatively uncharted territory and need more evidence from precision prevention RCTs. More tailored approaches combining multidomain lifestyle intervention and pharmacological treatment, for example the MET-FINGER RCT (lifestyle + metformin when appropriate), will provide specific insight on how to better prevent cognitive decline and dementia in specific target populations or individuals depending on their unique risk profile (Barbera et al., 2024). There is also growing interest in studying newer diabetes medications (e.g. GLP-1 agonists) in dementia/AD prevention and treatment, either alone or in combination with multidomain lifestyle interventions (Nowell et al., 2023).
References:
Stephen R, Barbera M, Peters R, Ee N, Zheng L, Lehtisalo J, Kulmala J, Håkansson K, Chowdhary N, Dua T, Solomon A, Anstey KJ, Kivipelto M.
Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions.
Front Neurol. 2021;12:763573. Epub 2021 Oct 26
PubMed.
Barbera M, Lehtisalo J, Perera D, Aspö M, Cross M, De Jager Loots CA, Falaschetti E, Friel N, Luchsinger JA, Gavelin HM, Peltonen M, Price G, Neely AS, Thunborg C, Tuomilehto J, Mangialasche F, Middleton L, Ngandu T, Solomon A, Kivipelto M, MET-FINGER study team.
A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol.
Alzheimers Res Ther. 2024 Jan 31;16(1):23.
PubMed.
Nowell J, Blunt E, Gupta D, Edison P.
Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease.
Ageing Res Rev. 2023 Aug;89:101979. Epub 2023 Jun 14
PubMed.
Comments
University of Eastern Finland
Finnish Institute for Health and Welfare
Karolinska Institutet
Wang and colleagues' interesting study showed that a multidisciplinary diabetes management program in primary care settings was associated with a reduced risk of dementia incidence among patients with T2D in a cohort study in Hong Kong. Patients with T2D who attended the Risk Assessment and Management Program-Diabetes Mellitus (RAMP-DM), had a 28 percent lower risk of all-cause dementia incidence compared with patients who did not attend the program and received only usual care. A significant risk reduction was seen also for dementia subtypes; Alzheimer’s disease, vascular dementia, and other or unspecified dementia (based on EHR data). A moderate glycaemic control target of HbA1C between 6.5 and 7.5 percent was associated with lower dementia incidence.
A surprising finding is that the dementia risk started to differ between groups immediately after the study onset. The authors conclude that “patients in the RAMP-DM group were still likely to have greater health consciousness than those in the usual care group, which may have led to differences in dementia incidence” and these could at least partially explain the results. On the other hand, it is also likely that clinical evaluation of patients in the RAMP-DM group, including cognitive assessment, was more comprehensive than in the usual care group leading to a more sensitive dementia diagnosis in the RAMP-DM group. Given all this, it is interesting that the study could still find significant differences between the two groups.
Although retrospective, this is a large study (55,618 participants) with a long follow-up (eight years), making its finding relevant and promising. It is challenging to study dementia incidence in randomized controlled trial (RCT) settings. This study clearly reinforces the link between T2D and dementia and its subtypes, and indicates that appropriate management has substantial long-term benefits also on the prevention and risk reduction of dementia.
Importantly, this study supports the ever-increasing body of evidence that dementia prevention/risk reduction interventions are most likely to succeed when they are multimodal, i.e., addressing multiple risk factors and mechanisms at the same time, multidisciplinary, tailored to the patient, sustainable, and sufficiently intensive (Stephen et al., 2021). In this study, RAMP-DM assessment was repeated continuously once every one to three years based on estimated risk level, and the patients were referred to a specialist for related diabetic complications. This risk-stratification process and multidisciplinary coordination enabled more individualized programs and can be one of the key factors behind the positive and strong findings.
The mean age at the time of dementia diagnosis was around 82 years, thus the study highlights the importance of adequate diabetes management even later in life. More work is needed to determine optimal glycaemic control targets (which may differ across age groups).
In general, in terms of identifying the most effective dementia risk reduction strategies for different at-risk populations, we are still in relatively uncharted territory and need more evidence from precision prevention RCTs. More tailored approaches combining multidomain lifestyle intervention and pharmacological treatment, for example the MET-FINGER RCT (lifestyle + metformin when appropriate), will provide specific insight on how to better prevent cognitive decline and dementia in specific target populations or individuals depending on their unique risk profile (Barbera et al., 2024). There is also growing interest in studying newer diabetes medications (e.g. GLP-1 agonists) in dementia/AD prevention and treatment, either alone or in combination with multidomain lifestyle interventions (Nowell et al., 2023).
References:
Stephen R, Barbera M, Peters R, Ee N, Zheng L, Lehtisalo J, Kulmala J, Håkansson K, Chowdhary N, Dua T, Solomon A, Anstey KJ, Kivipelto M. Development of the First WHO Guidelines for Risk Reduction of Cognitive Decline and Dementia: Lessons Learned and Future Directions. Front Neurol. 2021;12:763573. Epub 2021 Oct 26 PubMed.
Barbera M, Lehtisalo J, Perera D, Aspö M, Cross M, De Jager Loots CA, Falaschetti E, Friel N, Luchsinger JA, Gavelin HM, Peltonen M, Price G, Neely AS, Thunborg C, Tuomilehto J, Mangialasche F, Middleton L, Ngandu T, Solomon A, Kivipelto M, MET-FINGER study team. A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol. Alzheimers Res Ther. 2024 Jan 31;16(1):23. PubMed.
Nowell J, Blunt E, Gupta D, Edison P. Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease. Ageing Res Rev. 2023 Aug;89:101979. Epub 2023 Jun 14 PubMed.
View all comments by Miia KivipeltoMake a Comment
To make a comment you must login or register.