Association Between Diabetes and Hippocampal Atrophy in Elderly Japanese: The Hisayama Study

Abstract

OBJECTIVETo investigate the association between diabetes and brain or hippocampal atrophy in an elderly population. RESEARCH DESIGN AND METHODSA total of 1,238 community-dwelling Japanese subjects aged ‡65 years underwent brain MRI scans and a comprehensive health examination in 2012. Total brain volume (TBV), intracranial volume (ICV), and hippocampal volume (HV) were measured using MRI scans for each subject. We examined the associations between diabetes-related parameters and the ratios of TBV to ICV (an indicator of global brain atrophy), HV to ICV (an indicator of hippocampal atrophy), and HV to TBV (an indicator of hippocampal atrophy beyond global brain atrophy) after adjustment for other potential confounders. RESULTSThe multivariable-adjusted mean values of the TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios were significantly lower in the subjects with diabetes compared with those without diabetes (77.6% vs. 78.2% for the TBV-to-ICV ratio, 0.513% vs. 0.529% for the HV-to-ICV ratio, and 0.660% vs. 0.676% for the HV-to-TBV ratio; all P < 0.01). These three ratios decreased significantly with elevated 2-h postload glucose (PG) levels (all P for trend <0.05) but not fasting plasma glucose levels. Longer duration of diabetes was significantly associated with lower TBV-to-ICV, HV-to-ICV, and HV-to-TBV ratios. The subjects with diabetes diagnosed in midlife had significantly lower HV-to-ICV and HV-to-TBV ratios than those without and those diagnosed in late life. CONCLUSIONSOur data suggest that a longer duration of diabetes and elevated 2-h PG levels, a marker of postprandial hyperglycemia, are risk factors for brain atrophy, particularly hippocampal atrophy.

Comparative Effectiveness for Glycemic Control in Older Adults with Diabetes

“…38 A similar pattern was seen in another study showing higher degrees of atrophy in older adults with DM2, particularly in those with longer diabetes duration and higher fasting glucose levels. 39 …”

Prediabetes and structural brain abnormalities: Evidence from observational studies

“…Finally, 141 articles were excluded because they were animal studies (n = 9), unable to provide information (n = 120) or without a full publication (n = 12). The remaining 12 studies were enrolled in the meta‐analysis . There were 4 prospective cohort studies, 6 cross‐sectional studies and 2 with both cohort and cross‐sectional data studies .…”

“…The remaining 12 studies were enrolled in the meta‐analysis . There were 4 prospective cohort studies, 6 cross‐sectional studies and 2 with both cohort and cross‐sectional data studies . For continuous HbA 1c , 4 cohort studies investigated different structural brain abnormalities: 2 involved white matter hyperintensities, 3 involved infarct, and 2 involved brain volume).…”

“…For continuous HbA 1c , 4 cohort studies investigated different structural brain abnormalities: 2 involved white matter hyperintensities, 3 involved infarct, and 2 involved brain volume). For prediabetes, 8 cross‐sectional studies were chosen: 5 studies involved infarct, 3 studies involved white matter hyperintensities, 3 studies involved grey matter volume (including all kinds of grey matter), 2 studies involved hippocampal volume, 2 studies involved white matter volume, 2 studies involved total brain volume, and 2 studies involved cerebral microbleeds . Three cross‐sectional studies provided continuous data of the relationship between prediabetes and structural brain abnormalities (3 involved white volume and all kinds of grey matter volume, 2 involved total brain volume).…”

A Novel TREM2-Mediated Link between Diabetes and Cognitive Impairment: Recent Findings and Future Perspectives

“…Possible underlying mechanisms of diabetes-related dementia include multifactorial pathways implicated in hyperglycemic toxicity, microvascular diseases, chronic inflammatory processes, and changes in insulin metabolism, which ultimately lead to small vessel infarcts, neuroinflammation, amyloid-β accumulation and neurodegeneration in the brain [2][3][4][5]. Conversely, obesity has also been implicated to play a role in the development of dementia in later life [6]; however, a recent study reported an inverse monotonic association between body mass index (BMI) and dementia incidence [7].…”