Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study

Abstract

ObjectivesPossible association between diabetes mellitus (DM) and Alzheimer’s disease (AD) has been controversial. This study used a nationwide population-based dataset to investigate the relationship between DM and subsequent AD incidence.MethodsData were collected from Taiwan’s National Health Insurance Research Database, which released a cohort dataset of 1,000,000 randomly sampled people and confirmed it to be representative of the Taiwanese population. We identified 71,433 patients newly diagnosed with diabetes (age 58.74±14.02 years) since January 1997. Using propensity score, we matched them with 71,311 non-diabetic subjects by time of enrollment, age, gender, hypertension, hyperlipidemia, and previous stroke history. All the patients were followed up to December 31, 2007. The endpoint of the study was occurrence of AD.ResultsOver a maximum 11 years of follow-up, diabetic patients experienced a higher incidence of AD than non-diabetic subjects (0.48% vs. 0.37%, p<0.001). After Cox proportional hazard regression model analysis, DM (hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.50–2.07, p<0.001), age (HR, 1.11; 95% CI, 1.10–1.12, p<0.001), female gender (HR, 1.24; 95% CI, 1.06–1.46, p = 0.008), hypertension (HR, 1.30; 95% CI, 1.07–1.59, p = 0.01), previous stroke history (HR, 1.79; 95% CI, 1.28–2.50, p<0.001), and urbanization status (metropolis, HR, 1.32; 95% CI, 1.07–1.63, p = 0.009) were independently associated with the increased risk of AD. Neither monotherapy nor combination therapy with oral antidiabetic medications were associated with the risk of AD after adjusting for underlying risk factors and the duration of DM since diagnosis. However, combination therapy with insulin was found to be associated with greater risk of AD (HR, 2.17; 95% CI, 1.04–4.52, p = 0.039).ConclusionNewly diagnosed DM was associated with increased risk of AD. Use of hypoglycemic agents did not ameliorate the risk.

Cognitive impairment among type 2 diabetes mellitus patients at Jimma University Specialized Hospital, Southwest Ethiopia

“…In addition, a 9 years cohort study showed that T2DM patients would develop Alzheimer's disorders with 65% probabilities than non-diabetic populations (Arvanitakis et al, 2004). In addition, a very long 11 years cohort study reaffirms the incidence of Alzheimer diseases increases by 4.8% among T2DM patients (Huang et al, 2014). These findings supports that diabetes is a risk factor for neurological disorders including cognitive impairment.…”

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

“…Elderly people with diabetes have an especially increased risk of mild cognitive impairment (MCI) [18] and an association of diabetes with MCI varies with amyloid subtype (amnestic) MCI and nonamnestic MCI) and number of domains, and with the sex of the patient, with females being more susceptible than males [19]. Diabetes as a significant risk factor for dementia or AD has been clearly established by studies in the US [20] and several other countries (Taiwan [21], China [22], Japan [23], and Finland [24]). T2D has also been associated with an increased risk of vascular dementia [25], and pre-diabetic insulin resistance is a risk factor for AD pathology and reduced memory function [26].…”

Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo

“…Although both Aβ and tau are central to AD pathogenesis, it is unclear whether glucose dysregulation is an initiator of AD pathology, a secondary consequence of neuronal dysfunction due to Aβ and tau deposition, or both. Recent epidemiological studies demonstrate that individuals with type 2 diabetes (T2DM) are 2-4 times more likely to develop AD (3)(4)(5), individuals with elevated blood glucose levels are at an increased risk to develop dementia (5), and those with elevated blood glucose levels have a more rapid conversion from mild cognitive impairment (MCI) to AD (6), suggesting that disrupted glucose homeostasis could play a more causal role in AD pathogenesis. Although several prominent features of T2DM, including increased insulin resistance and decreased insulin production, are at the forefront of AD research (7)(8)(9)(10), questions regarding the effects of elevated blood glucose independent of insulin resistance on AD pathology remain largely unexplored.…”