Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study

• Published in: Diabetologia Vol. 61; no. 9; pp. 1956 - 1965
• Main Authors: Lee, Alexandra K., Rawlings, Andreea M., Lee, Clare J., Gross, Alden L., Huang, Elbert S., Sharrett, A. Richey, Coresh, Josef, Selvin, Elizabeth
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2018; Springer Nature B.V
• Subjects: Aged; Apolipoprotein E; Apolipoproteins E - genetics; Arteriosclerosis; Atherosclerosis; Brain - diagnostic imaging; Brain - physiopathology; Cognition; Cognitive ability; Cognitive Dysfunction - complications; Cognitive Dysfunction - physiopathology; Cohort analysis; Cohort Studies; Cross-Sectional Studies; Dementia; Dementia - complications; Dementia - physiopathology; Dementia disorders; Demography; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Epidemiology; Female; Genotype; Genotypes; Human Physiology; Humans; Hypoglycemia; Internal Medicine; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Neuropsychological Tests; Older people; Organ Size; Survival analysis; Cognitive decline; Type 2 diabetes; Hypoglycaemia; Brain volume; Epidemiology; Cognitive impairment; Dementia
• ISSN: 0012-186X; 1432-0428; 1432-0428
• DOI: 10.1007/s00125-018-4668-1

Aims/hypothesis
We aimed to evaluate the link between severe hypoglycaemia and domain-specific cognitive decline, smaller brain volumes and dementia in adults with type 2 diabetes, which so far has been relatively poorly characterised.
Methods
We included participants with diagnosed diabetes from the community-based Atherosclerosis Risk in Communities (ARIC) study. At the participants’ fifth study visit (2011–2013), we examined the cross-sectional associations of severe hypoglycaemia with cognitive status, brain volumes and prior 15 year cognitive decline. We also conducted a prospective survival analysis of incident dementia from baseline, visit 4 (1996–1998), to 31 December 2013. Severe hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency department visits and ambulance records. Prior cognitive decline was defined as change in neuropsychological test scores from visit 4 (1996–1998) to visit 5 (2011–2013). At visit 5, a subset of participants underwent brain MRIs. Analyses were adjusted for demographics,
APOE
genotype, use of diabetes medication, duration of diabetes and glycaemic control.
Results
Among 2001 participants with diabetes at visit 5 (mean age 76 years), a history of severe hypoglycaemia (3.1% of participants) was associated with dementia (vs normal cognitive status): OR 2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain MRI (
n
 = 580), hypoglycaemia was associated with smaller total brain volume (−0.308 SD, 95% CI −0.612, −0.004). Hypoglycaemia was nominally associated with a 15 year cognitive change (−0.14 SD, 95% CI −0.34, 0.06). In prospective analysis (
n
 = 1263), hypoglycaemia was strongly associated with incident dementia (HR 2.54, 95% CI 1.78, 3.63).
Conclusions/interpretation
Our results demonstrate a strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting a need for discussion of appropriate diabetes treatments for high-risk older adults.