Cognitive disorder and dementia in type 2 diabetes mellitus

Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and brain.In the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative diseases.At the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are decreased.Clinical and animal model studies suggest that memory improvements are due to changes in insulin levels.Furthermore,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis development.Conversely, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, and could be a specific target for therapeutic strategies to decreasealterations associated with age-related cognitive decline.

Alterations in blink and masseter reflex latencies in older adults with neurocognitive disorder and/or diabetes mellitus

BACKGROUND Blink and masseter reflexes provide reliable,quantifiable data on the function of the central nervous system:Delayed latencies have been found in patients with neurocognitive disorder(ND)and type 2 diabetes mellitus(T2DM),but this has not been studied in patients with both pathologies.AIM To investigate if older adults with ND plus T2DM have prolonged latencies of blink and masseter-reflex and if they were associated with disease progression.METHODS This cross-sectional study included 227 older adults(>60 years)from Colima,Mexico.Neurocognitive disorder was identified by a neuropsychological battery test,and T2DM identified by medical history,fasting glucose,and glycosylated hemoglobin.Latencies in the early reflex(R1),ipsilateral late(R2),and contralateral late(R2c)components of the blink reflex were analyzed for all subjects,and 183 subjects were analyzed for latency of the masseter reflex.RESULTS In 20.7%of participants,ND was detected.In 37%,T2DM was detected.Latencies in R1,R2,and R2c were significantly prolonged for groups with ND plus T2DM,ND,and T2DM,compared with the control group(P<0.0001).The masseter reflex was only prolonged in older adults(regardless of T2DM status)with ND vs controls(P=0.030).In older adults with ND and without T2DM,the more the cognitive impairment progressed,the more prolonged latencies in R2 and R2c presented(P<0.01).CONCLUSION These findings suggest that blink and masseter reflexes could be used to evaluate possible changes in brainstem circuits in older adults with ND and T2DM.