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Significant Association Found Between Age of Diabetes Onset and Subsequent Dementia

Investigators analyzed electronic health records from 10,095 participants over a median follow-up period of 31.7 years.

A longitudinal cohort study published in JAMA has identified a link between the age of onset of type 2 diabetes and the risk of dementia, concluding that patients diagnosed with type 2 diabetes at a younger age were consequently diagnosed with dementia at a younger age. 

A total of 10,095 participants were included in study analyses, with investigators reporting a total of 1710 (16.9%) cases of diabetes and 639 (6.3%) cases of dementia over the median follow-up period of 31.7 years (1985-2019). Investigators saw a higher increased hazard of dementia with every 5-year earlier onset of diabetes, with dementia rates per 1000 person-years at 8.9 participants in participants without diabetes at 70 years; 10.0 per 1000 person-years for participants with diabetes onset up to 5 years earlier; and 18.3 for over 10 years earlier.

Data were then compared to patients without diabetes at age 70, finding hazards of dementia increased as it correlated to onset age of diabetes (P <.001). Investigators calculated hazard ratio (HR) of dementia in patients who developed type 2 diabetes over 10 years prior (HR, 2.12 [95% CI, 1.503.00]); 6 to 10 years prior (HR, 1.49 [95% CI, 0.95-2.32]); and 0 to 5 years prior (HR, 1.11 [95% CI, 0.70-1.76]). At age 70, it was concluded that every 5-year younger age increment of onset of type 2 diabetes was significantly associated with hazard of dementia (HR, 1.24 [95% CI, 1.06-1.46]). 

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“Meta-analyses of the association between type 2 diabetes and dementia reported a risk ratio between 1.43 and 1.62,” lead author Claudio Barbiellini Amidei, MD, department of cardiac, thoracic, and vascular science, University of Padua, Italy, wrote.1 “These estimates are in line with results in the present study of a hazard ratio of 1.52 when all diabetes cases were considered in the analyses, including those occurring after 70 years of age.”

Investigators found no association between late-onset diabetes and subsequent dementia, and no strong association of dementia with preclinical diabetes. However, it was found that those with diabetes and cardiovascular comorbidities such as coronary heart disease, heart failure, or stroke were at a higher risk to develop dementia. Stroke was significantly associated, with 9 dementia cases in 58 persons and a dementia rate of 24.32/1000 person-years (HR, 4.99 [95% CI, 2.19-11.37]).

Limitations of the study included the inability to distinguish between dementia subtypes, namely Alzheimer disease and vascular dementia, and diabetes correlation, as well as the rates of diabetes (16.5%) and dementia (6.3%) being lower in the study than rates in the general UK population. Investigators were also unable to account for data on glycated hemoglobin, a diabetes status marker, until later in the study, and electronic health records were used to account for dementia diagnoses rather than in-person evaluations. As participants were between 69 and 89 years of age at the conclusion of the follow-up, with the younger portion yet to reach an age where dementia becomes more prevalent, further study is necessitated to explore the age of onset.

“To date, studies that explicitly consider age at diabetes onset or diabetes duration remain scarce, primarily because studies on dementia recruit participants older than 65 years and age at diabetes onset is not known with precision or not taken into consideration,” Barbiellini et al wrote, noting an exception in the Swedish Twin Registry study, where diabetes was associated with dementia before 65 years of age (odds ratio [OR], 2.41 [95% CI 1.05-5.51]), but not after (OR, 0.68 [95% CI, 0.30-1.53]).1 

“Results from the US ARIC study, based on persons aged 66 to 90 years at start of follow-up, suggest longer diabetes duration to be associated with higher risk of dementia only in the youngest age tertile,” Barbiellini et al said.1 “Longer duration of diabetes has also been associated with faster cognitive decline. Careful analysis of age of diabetes onset in the present study, along with explicit examination of duration of diabetes, showed a graded association between age at onset of diabetes and dementia risk.” 

The study was sponsored by the National Institute on Aging, in working toward their milestone to better understand connections amongst cerebro- and cardiovascular disease, as well as vascular contributions to cognitive impairment and dementia risk factors, aging, resilience, genetics, amyloid, tau, and neurogeneration interrelationships. The associated milestone is specific to Alzheimer disease and Alzheimer disease-related dementias.

REFERENCES
1. Barbiellini Amidei C, Fayosse A, Dumurgier J, et al. Association Between Age at Diabetes Onset and Subsequent Risk of Dementia. JAMA. 2021;325(16):1640–1649. doi:10.1001/jama.2021.4001
2. Study links younger age of onset of type 2 diabetes to increased risk of dementia. News release. National Institute on Aging. July 22, 2021. Accessed August 2, 2021. https://www.nia.nih.gov/news/study-links-younger-age-onset-type-2-diabetes-increased-risk-dementia