Abstract
Type 2 diabetes mellitus (DM) has been shown to increase the risk for cognitive decline and dementia, such as in Alzheimer disease (AD) and vascular dementia (VaD). Additionally, there may be a dementia subgroup associated with specific DM-related metabolic abnormalities rather than with AD pathology or cerebrovascular diseases. This type of dementia, not showing hypoperfusion in the parietotemporal lobe on SPECT or cerebrovascular lesions on MRI, was characterized by old age, high hemoglobin A1c level, long duration of diabetes, high frequency of insulin therapy, low frequency of apolipoprotein E4 carrier, less-severe medial temporal lobe atrophy, impaired attention and executive function, less-impaired word recall, and slow progression of cognitive impairment and might be referred to as "diabetes-related dementia" (DrD). 11C-Pittsburgh compound-B PET shows often negative or equivocal amyloid accumulation in the brain, indicating different from AD pathology. In addition to insulin resistance, elevated inflammatory cytokines, oxidative stress, and advanced glycation end products were associated with cognitive impairment in this type of dementia. Glycemic controls can improve some domains of cognitive function, such as attention and executive functions, in subjects with DrD. Frequencies of frailty and sarcopenia/dynapenia are significantly higher in DrD than in AD, indicating that geriatric interventions are necessary to improve clinical outcomes for patients with DrD. DrD can be considered as a controllable or modifiable dementia. The identification of DrD, as distinct from other types of dementia, may be necessary for considering appropriate therapy and prevention in clinical practice.
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