Key PointsQuestionWhat is the association between age at onset of type 2 diabetes
and subsequent risk of dementia? FindingsIn this prospective cohort study of 10095
participants, younger age at onset of type 2 diabetes was significantly associated
with higher risk for incident dementia; at age 70, the hazard ratio for every 5-year
earlier age at type 2 diabetes onset was 1.24. MeaningYounger age at diabetes onset
was associated with higher risk of subsequent dementia. ImportanceTrends in type 2
diabetes show an increase in prevalence along with younger age of onset. While vascular
complications of early-onset type 2 diabetes are known, the associations with dementia
remains unclear. ObjectiveTo determine whether younger age at diabetes onset is more
strongly associated with incidence of dementia. Design, Setting, and ParticipantsPopulation-based
study in the UK, the Whitehall II prospective cohort study, established in 1985-1988,
with clinical examinations in 1991-1993, 1997-1999, 2002-2004, 2007-2009, 2012-2013,
and 2015-2016, and linkage to electronic health records until March 2019. The date
of final follow-up was March 31, 2019. ExposuresType 2 diabetes, defined as a fasting
blood glucose level greater than or equal to 126 mg/dL at clinical examination, physician-diagnosed
type 2 diabetes, use of diabetes medication, or hospital record of diabetes between
1985 and 2019. Main Outcomes and MeasuresIncident dementia ascertained through linkage
to electronic health records. ResultsAmong 10095 participants (67.3% men; aged 35-55
years in 1985-1988), a total of 1710 cases of diabetes and 639 cases of dementia were
recorded over a median follow-up of 31.7 years. Dementia rates per 1000 person-years
were 8.9 in participants without diabetes at age 70 years, and rates were 10.0 per
1000 person-years for participants with diabetes onset up to 5 years earlier, 13.0
for 6 to 10 years earlier, and 18.3 for more than 10 years earlier. In multivariable-adjusted
analyses, compared with participants without diabetes at age 70, the hazard ratio
(HR) of dementia in participants with diabetes onset more than 10 years earlier was
2.12 (95% CI, 1.50-3.00), 1.49 (95% CI, 0.95-2.32) for diabetes onset 6 to 10 years
earlier, and 1.11 (95% CI, 0.70-1.76) for diabetes onset 5 years earlier or less;
linear trend test (P<.001) indicated a graded association between age at onset of
type 2 diabetes and dementia. At age 70, every 5-year younger age at onset of type
2 diabetes was significantly associated with an HR of dementia of 1.24 (95% CI, 1.06-1.46)
in analyses adjusted for sociodemographic factors, health behaviors, and health-related
measures. Conclusions and RelevanceIn this longitudinal cohort study with a median
follow-up of 31.7 years, younger age at onset of diabetes was significantly associated
with higher risk of subsequent dementia. This cohort study uses UK Whitehall cohort
data to examine the association between age at type 2 diabetes onset and incident
dementia.
