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Diabetes mellitus and risk of dementia: A meta‐analysis of prospective observational studies
Open accessAbstract
Aims/Introduction: The aim of the present study was to investigate the association between diabetes and the risk of all type dementia ( ATD ), A lzheimer's disease ( AD ) and vascular dementia ( VaD ). Materials and Methods: Prospective observational studies describing the incidence of ATD , AD and VaD in patients with diabetes mellitus were extracted from PubMed, EMBASE and other databases up to January 2012. Pooled relative risk ( RR ) estimates and 95% confidence intervals ( CI s) were calculated using the random‐effects model. Subgroup analyses and sensitivity analysis were also carried out. Results: A total of 28 studies contributed to the analysis. Pooled RR of developing ATD ( n = 20) was 1.73 (1.65–1.82, I 2 = 71.2%), AD ( n = 20) was 1.56 (1.41–1.73, I 2 = 9.8%) and VaD ( n = 13) was 2.27 (1.94–2.66, I 2 = 0%) in patients with diabetes mellitus. Higher and medium quality studies did not show any significant difference for pooled RR for ATD , AD or VaD . Sensitivity analyses showed robustness of pooled RR among ATD , AD and VaD , showing no single study had a major impact on pooled RR . Conclusions: The results showed a 73% increased risk of ATD , 56% increase of AD and 127% increase of VaD in diabetes patients.
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“These factors include hypertension 85,[105][106][107] and diabetes.[108][109][110]”
From 2023 Alzheimer's disease facts and figures (2023) · cites this paper as [108]
In the citing paper
“A meta-analysis of prospective and observational studies in PWD showed a 73% increased risk of all types of dementia, a 56% increased risk of Alzheimer dementia, and a 127% increased risk of vascular dementia compared with individuals without diabetes (115).”
From Psychosocial care for people with diabetes: a position statement of the American Diabetes Association (2016) · cites this paper as [115]
In the citing paper
“A meta-analysis of prospective and observational studies in PWD showed a 73% increased risk of all types of dementia, a 56% increased risk of Alzheimer dementia, and a 127% increased risk of vascular dementia compared with individuals without diabetes (115).”
From Psychosocial care for people with diabetes: a position statement of the American Diabetes Association (2016) · cites this paper as [115]
In the citing paper
“A meta-analysis of prospective and observational studies in PWD showed a 73% increased risk of all types of dementia, a 56% increased risk of Alzheimer dementia, and a 127% increased risk of vascular dementia compared with individuals without diabetes (115).”
From Psychosocial care for people with diabetes: a position statement of the American Diabetes Association (2016) · cites this paper as [115]
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MethodDegeneration of Dopaminergic Neurons Due to Metabolic Alterations and Parkinson’s Disease
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“There is mounting evidence that diabetes mellitus increases the risk of dementia, cognitive impairment, or cognitive decline (Gudala et al., 2013; Baumgart et al., 2015; Magliano et al., 2019).”
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Chronic Kidney Disease and Cognitive Impairment
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“[3] published a meta-analysis of DM cases and the risk of all types of dementia (including AD) based on 28 prospective observational studies conducted on a total of 89708 patients with diabetesmellitus in comparison to a nondiabetic control group [3].”
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Diabetes and cognitive decline
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“…mild cognitive impairment, dementia and Alzheimer's disease, as shown by numerous epidemiological studies (Craft, 2007; Matsuzaki et al., 2010; Sima, 2010; Schrijvers et al., 2010; Umegaki, 2010; Viscogliosi et al., 2012; Gudala et al., 2013; Calvo-Ochoa and Arias, 2015; Hoscheidt et al., 2016).”
Disturbed sleep and diabetes: A potential nexus of dementia risk
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Depletion of Caveolin-1 in Type 2 Diabetes Model Induces Alzheimer's Disease Pathology Precursors
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“The combined overall relative risk for dementia, including clinical diagnoses of both AD and vascular dementia, is 73% higher in people with T2DM than in those without (Gudala et al., 2013; Biessels et al., 2014).”
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The Association between Hepatic Encephalopathy and Diabetic Encephalopathy: The Brain-Liver Axis
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“Patients with diabetes show a higher risk of dementia than do healthy individuals in clinical studies [17], and there is a considerable correlation between”
BackgroundDementia in Diabetes: The Role of Hypoglycemia
Husain, K. H., Sarhan, S. F., AlKhalifa, H. K. A. A., Buhasan, A., Moin, A. S. M., & Butler, A. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24129846 · Cited by 52
“A meta-analysis of 28 prospective observational studies determined that individuals with diabetes have a 73% greater risk of developing all-cause dementia (dementia not limited to a certain type), with a 56% and 127% increased risk of AD and vascular dementia, respectively [13].”
MethodThe growing range of complications of diabetes mellitus
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The Glymphatic System in Diabetes-Induced Dementia
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“A recent meta-analysis indicated that individuals with T2DM have a 65% increased risk for Alzheimer’s disease (AD) (2).”
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“A year later, another meta-analysis considering a total of 28 studies reported a pooled RR of 1.56 (95% CI = 1.41–1.73) for developing AD and 2.3 for developing vascular dementia 2.27 (95% CI = 1.94–2.66) in patients with T2DM [35].”
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“25 to 2 times higher than that in patients without diabetes (Gudala et al., 2013; Xue et al., 2019).”
BackgroundPelle, M. C., Zaffina, I., Giofrè, F., Pujia, R., & Arturi, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411301 · Cited by 50
“According to a previous meta-analysis that included 28 observational studies, individuals with diabetes have an increased risk of 73% for all types of dementia, 56% for AD, and 127% for vascular dementia (VaD) [34].”
MethodGlycemia, Diabetes Status, and Cognition in Hispanic Adults Aged 55–64 Years
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“In addition to well-recognized complications like retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disorders, DM is now a well-established risk factor for dementia [3].”
BackgroundKim, Y., Jeon, J. Y., Kim, H. J., Kim, D. J., Lee, K. W., Moon, S. Y., & Han, S. J. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm8010028 · Cited by 47
“According to a recent meta-analysis of 28 prospective observational studies, patients with diabetes have a 73% higher risk of dementia compared to those without diabetes [5].”
MethodLiu, D., Chen, J., Jian, W., Zhang, G.-R., & Liu, Z.-R. (2019) · PubMed Central · doi:10.11909/j.issn.1671-5411.2019.03.006 · Cited by 47
Bao, H., Liu, Y., Zhang, M., Chen, Z., Zhang, W., Ge, Y., Kang, D., Gao, F., & Shen, Y. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12276 · Cited by 45
“; (4) participants unable to co-operatewith doctors; (5) participants diagnosedasprobableT1DMandother special types of diabetes; (6) no adequate blood samples for further detection of blood-based biomarkers and analyses.”
BackgroundBai, A., Tao, L., Huang, J., Tao, J., & Liu, J. (2021) · BMC Public Health · doi:10.1186/s12889-021-10537-x · Cited by 44
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“5 fold (Gudala et al., 2013; Koenig et al., 2017), indicating that diabetes is an important risk factor for cognitive impairment (Desmond et al.”
BackgroundIs Alzheimer's disease a type 3 diabetes? A review
Janoutová, J., Machaczka, O., Zatloukalová, A., & Janout, V. (2022) · Central European Journal of Public Health · doi:10.21101/cejph.a7238 · Cited by 44
“The results showed a 73% increased risk of all type dementia, 56% increase of Alzheimer’s disease and 127% increase of vascular dementia in diabetes patients (13).”
BackgroundTargeting Thrombin: An Inflammatory Neurotoxin in Alzheimer's Disease
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“A recent metaanalysis of prospective observational studies extracted from databases up to January 2012 shows that diabetes increases the risk of all types of dementia 73% and AD specifically by 56% [18].”
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“51) was virtually identical to estimates obtained in prior meta-analyses of studies using Cox models [2, 3].”
MethodDrug Repositioning for Alzheimer’s Disease: Finding Hidden Clues in Old Drugs
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Diabetes Mellitus Increases Risk of Incident Dementia in APOE ɛ 4 Carriers: A Meta-Analysis
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“In a meta-analysis of prospective studies, diabetes increased the relative risk of AD by 56% [10].”
Background2026 Alzheimer's disease facts and figures
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Metformin a Potential Pharmacological Strategy in Late Onset Alzheimer’s Disease Treatment
Poor, S. R., Ettcheto, M., Cano, A. C., Sánchez‐López, E., Manzine, P. R., Olloquequi, J., Camins, A., & Javan, M. (2021) · Pharmaceuticals · doi:10.3390/ph14090890 · Cited by 41
“A retrospective study of 20 prospective clinical trials concluded that the prevalence of LOAD in patients with T2DM was 56% greater than in people without diabetes [21].”
BackgroundInfluentialJeong, J., Lee, D. H., & Song, J. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112933 · Cited by 40
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Blood glucose levels and cortical thinning in cognitively normal, middle-aged adults
Wennberg, A. M. V., Spira, A. P., Pettigrew, C. A., Soldan, A., Zipunnikov, V. M., Rebok, G. W., Roses, A. D., Lutz, M. W., Miller, M. M., Thambisetty, M., et al. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.04.017 · Cited by 41
“Past research has established that DM is a risk factor for dementia [30], with one study estimating that 6–10% of dementia cases are directly attributable to DM [37].”
BackgroundBRIDGING THE TRANSLATION GAP: FROM DEMENTIA RISK ASSESSMENT TO ADVICE ON RISK REDUCTION
Anstey, K. J., Eramudugolla, R., Hosking, D. E., Lautenschlager, N. T., & Dixon, R. A. (2015) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2015.75 · Cited by 40
Chen, B., Teng, Y., Zhang, X., Lv, X., & Yin, Y. (2016) · BioMed Research International · doi:10.1155/2016/1421430 · Cited by 39
“Nowadays, the scientists have laidmore andmore emphasis on the relationship betweenAD and diabetes, and diabetes has absolutely been considered as a risk factor for AD [9].”
Infante‐Garcia, C., & García-Alloza, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20102533 · Cited by 40
Brain insulin resistance impairs hippocampal plasticity
Spinelli, M., Fusco, S., & Grassi, C. (2020) · Vitamins and hormones · doi:10.1016/bs.vh.2020.04.005 · Cited by 39
Kumar, A., Kumar, A., Jaggi, A. S., & Singh, N. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.05.006 · Cited by 38
Rhizoma Coptidis for Alzheimer’s Disease and Vascular Dementia: A Literature Review
Wang, Z., Yang, Y., Liu, M., Wei, Y., Liu, J., Pei, H., & Li, H. (2019) · Current Vascular Pharmacology · doi:10.2174/1570161117666190710151545 · Cited by 38
Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia
Al-Janahi, E., Ponirakis, G., Hamad, H. K. A., Vattoth, S., Elsotouhy, A., Petropoulos, I. N., Khan, A., Gad, H., Chandran, M., Sankaranarayanan, A., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200678 · Cited by 41
“Epidemiological studies also show that individuals with T2D have an increased risk of dementia [39, 40].”
LACY, M. E., Moran, C., Gilsanz, P., Beeri, M. S., Karter, A. J., & Whitmer, R. A. (2022) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2021-002557 · Cited by 39
Li, Z., Lin, C., Cai, X., Lv, F., Yang, W., & Ji, L. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01645-y · Cited by 44
“Moreover, after adjusting the effects of blood glucose and diabetic complications, the risks of dementia in patients with diabetes were still greater than healthy populations [14].”
Prevalence and Incidence of Dementia in People with Diabetes Mellitus
Alsharif, A. A., Wei, L., Ma, T., Man, K. K. C., Lau, W. C. Y., Brauer, R., AlMetwazi, M. S., Howard, R. J., & Wong, I. C. K. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191115 · Cited by 39
“In 2013, a meta-analysis of 28 prospective observational studies investigated the association between diabetes and the risk of dementia, and found that diabetes was associated with a 73% increased risk of all types of dementia compared to non-diabetic people [7].”
Onset age of diabetes and incident dementia: A prospective cohort study
Wang, Y., Li, C., Liang, J., Gao, D., Pan, Y., Zhang, W., Zhang, Y., Zheng, F., & Xie, W. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.02.138 · Cited by 36
Tian, Y., Jing, G., Ma, M., Yin, R., & Zhang, M. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105848 · Cited by 39
“Among these, patients with T2D have a 50 – 100 % increased risk of Alzheimer ’ s disease (AD), a 100 – 150 % increased risk of vascular dementia (Gudala et al., 2013; Zhang et al., 2017), and a 1.53-fold increased risk of progressing from mild cognitive impairment to dementia (Xue et al., 2019).”
BackgroundInfluentialDementia-like pathology in type-2 diabetes: A novel microRNA mechanism
Kalani, A., Chaturvedi, P., Maldonado, C. J., Bauer, P. M., Joshua, I. G., Tyagi, S. C., & Tyagi, N. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.02.005 · Cited by 36
“A meta-analysis performed on 28 studies suggests that diabetic patients face increased risk of AD by 56% and VaD by 127% (Gudala et al., 2013).”
Griffin, J. W. D., Liu, Y., Bradshaw, P. C., & Wang, K. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1035-0 · Cited by 36
Dyer, A. H., McKenna, L., Batten, I., Jones, K. M., Widdowson, M., Dunne, J., Conlon, N. P., Reilly, R. B., Woods, C. P., O’Neill, D. J., et al. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.605878 · Cited by 36
Ma, J., Yang, Y., Wan, Y., Shen, C., & Qiu, P. (2021) · PLoS ONE · doi:10.1371/journal.pone.0256297 · Cited by 35
“For example, several systematic reviews have shown an increased risk of cognitive decline among individuals with diabetes [24,25].”
BackgroundOchiai, T., Sano, T., Nagayama, T., Kubota, N., Kadowaki, T., Wakabayashi, T., & Iwatsubo, T. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105510 · Cited by 36
“5 times higher in patients with type 2 diabetes mellitus (T2DM) (Biessels et al., 2006; Gudala et al., 2013).”
BackgroundInfluentialAcetylation in pathogenesis: Revealing emerging mechanisms and therapeutic prospects
Jiang, N., Li, W., Jiang, S., Xie, M., & Liu, R. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115519 · Cited by 38
The Effects of Type 2 Diabetes on Cognitive Performance: A Review of Reviews
Sola, T., Sola, F.-M., & Jehkonen, M. (2024) · International Journal of Behavioral Medicine · doi:10.1007/s12529-024-10274-6 · Cited by 37
“We believe the information from this review will help researchers to plan future studies and clinicians to identify the cognitive domains potentially affected by T2DM. appli-dementia and Alzheimer’s disease at a later age [3].”
Heinemeyer, T., Stemmet, M., Bardien, S., & Neethling, A. (2018) · DNA and Cell Biology · doi:10.1089/dna.2018.4292 · Cited by 35
“Diabetes mellitus (DM) is thought to be an established risk factor for dementia (Gudala et al. , 2013) and studies have shown that diabetics exhibit reduced mean cortical thickness and reduced thickness in AD-vulnerable brain regions, in comparison to nondiabetics (Moran et al. , 2015).”
Batista, Â. G., Mendonça, M. C. P., Soares, E. S., da Silva-Maia, J. K., Dionísio, A. P., Sartori, C. R., da Cruz‐Höfling, M. A., & Maróstica, M. R. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103745 · Cited by 35
Bleomycin modulates amyloid aggregation in β-amyloid and hIAPP
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O-GlcNAc cycling in the developing, adult and geriatric brain
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“Metabolic disease is a risk factor for developing dementia, and symptom progression in dementia has been slowed with drugs potentiating insulin signaling in rodents and in humans (Gudala et al. 2013; Moreira 2012; Bobsin and Kreienkamp 2015; Cooper et al. 2015; Bomfim et al. 2012; De Felice et al. 2009; Escribano et a…”
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BackgroundLinking multiple pathogenic pathways in Alzheimer’s disease
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“Type 2 diabetes (T2D) is an important risk factor for dementia: People with T2D have signi fi cantly higher risk for dementia than those without (3 – 5).”
Zheng, B., Su, B., Ahmadi‐Abhari, S., Kapogiannis, D., Tzoulaki, I., Riboli, E., & Middleton, L. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13349 · Cited by 34
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“A meta-analysis of 20 prospective observational studies concluded that the occurrence of LOAD in individuals with T2DM was 56% higher compared to those without diabetes [34].”
Metadata
- Authors
- Gudala, K., Bansal, D., Schifano, F., & Bhansali, A.
- Affiliations
- National Institute of Pharmaceutical Education and Research (IN)
- University of Hertfordshire (GB)
- Post Graduate Institute of Medical Education and Research (IN)
- Corresponding author
- Bansal, Dipika
- Venue
- Journal of Diabetes Investigation
- Publisher
- Wiley
- Published
- 2013-04-26
- Volume
- 4
- Issue
- 6
- Pages
- 640-650
- ISSN
- 2040-1116 (ISSN-L)
- 2040-1124
- PMC
- PMC4020261
- OpenAlex
- W2035873080
- Cited by
- 727
- References
- 57
- Citations by year
- 2026: 69 · 2025: 90 · 2024: 73 · 2023: 61 · 2022: 84 · 2021: 61 · 2020: 80 · 2019: 66 · 2018: 37 · 2017: 44 · 2016: 35 · 2015: 20 · 2014: 5
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Diabetes Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- diabetes mellitus, dementia, Alzheimer's disease, vascular dementia, dementia risk, incidence, type 2 diabetes
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