Affiliation:
1. Metabolic Disease Research Unit, National Institute of Medical Sciences and Nutrition, Mexico, United States
2. Department of Geriatrics, National Institute of Medical Sciences and Nutrition, Mexico, United States
3. Department of Endocrinology and Metabolism, National Institute of Medical Sciences and Nutrition, Mexico, United States
Abstract
Background:
Type 2 diabetes represents an increasing health burden world-wide and its
prevalence in particularly higher in elderly population. Consistent epidemiological evidence suggests
an increased risk of dementia associated to type 2 diabetes; the mechanisms underlying these associations,
however, remain unclear.
Objective:
The study aims to review epidemiological, clinical and pre-clinical data that weigh on
pathophysiological links, mechanisms of disease and associations between type 2 diabetes and dementia
to identify areas of opportunity for future research.
Methods:
We searched the following electronic bibliographic databases: PUBMED, EMBASE,
SCIELO, MEDLINE and OVID for clinical, translational and epidemiological research literature that
summarize diabetes-related risk factors for dementia, metabolic and neurological changes associated to
T2D, evidence of therapeutic approaches in type 2 diabetes and its pathophysiological implications for
dementia.
Results:
Type 2 diabetes mellitus increases risk for all-cause dementia, vascular dementia and Alzheimer’s
disease. The most evaluated mechanisms linking both disorders in pre-clinical studies include
an increase in neuronal insulin resistance, impaired insulin signaling, pro-inflammatory state, mitochondrial
dysfunction and vascular damage which increase deposition of β-amyloid, tau proteins and
GSK3β, leading to an earlier onset of dementia in individuals with impairment in the glucose metabolism.
Neuroimaging and neuropathology evidence linking cerebrovascular lesions, neurodegeneration
and particularly small-vessel disease in the onset of dementia is consistent with the increased risk of
incident dementia in type 2 diabetes, but consistent evidence of AD-related pathology is scarce. Epidemiological
data shows increased risk of dementia related to hypoglycemic episodes, glycemic control,
metabolic syndrome, insulin resistance and genetic predisposition, but the evidence is not consistent
and statistical analysis might be affected by inconsistent covariate controlling. Therapeutic approaches
for T2D have shown inconsistent result in relation to dementia prevention and delay of cognitive
decline; lifestyle intervention, particularly physical activity, is a promising alternative to ameliorate
the impact of disability and frailty on T2D-related dementia.
Conclusion:
Vascular disease, inflammation and impaired brain insulin signaling might occur in T2D
and contribute to dementia risk. Evidence from epidemiological studies has not consistently reported
associations that could integrate a unified mechanism of disease in humans. Evaluation of the effect of
antidiabetic medications and non-pharmacological interventions in dementia prevention in type 2 diabetes
is promising but has thus far offered inconsistent results.
Publisher
Bentham Science Publishers Ltd.
Subject
Endocrinology,Endocrinology, Diabetes and Metabolism
Cited by
62 articles.
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