Alzheimer's disease and insulin resistance
Evidence continues to accumulate for the role of insulin resistance and type 2 diabetes in Alzheimer's disease. Research just published in Archives of Neurology add more certainty to the association. The authors observe:
"Insulin resistance is a causal factor in prediabetes (PD) and type 2 diabetes (T2D) and increases the risk of developing Alzheimer disease (AD). Reductions in cerebral glucose metabolic rate (CMRglu)...in parietotemporal, frontal, and cingulate cortices are associated with increased AD risk and can be observed years before dementia onset."
They structured their investigation by setting out to...
"...examine whether greater homeostasis model assessment insulin resistance (HOMA-IR) is associated with reduced resting CMRglu in areas vulnerable in AD in cognitively normal adults with newly diagnosed PD or T2D (PD/T2D), and to determine whether adults with PD/T2D have abnormal patterns of CMRglu during a memory encoding task."
They correlated data on adults with glycemic criteria for pre-diabetes or T2DM (and normal controls) with PET imaging of brain glucose metabolism and memory tests. They also examined the cerebral metabolic glucose rate (CMRglu) during the memory task. What did the data show?
"Greater insulin resistance was associated with an AD-like pattern of reduced CMRglu in frontal, parietotemporal, and cingulate regions in adults with PD/T2D. The relationship between CMRglu and HOMA-IR was independent of age, 2-hour OGTT glucose concentration, or apolipoprotein E {varepsilon}4 allele carriage...Adults with PD/T2D showed a qualitatively different pattern during the memory encoding task, characterized by more diffuse and extensive activation, and recalled fewer items on the delayed memory test."
Their conclusion suggests both the role of insulin resistance in the development of AD as well as its use as an early indicator of risk:
"Insulin resistance may be a marker of AD risk that is associated with reduced CMRglu and subtle cognitive impairments at the earliest stage of disease, even before the onset of mild cognitive impairment."
Interestingly, these findings were published along with another study in the same journal that reports on the accuracy of a constellation of blood test indicators for early diagnosis of AD. The authors set out...
"To develop an algorithm that separates patients with Alzheimer disease (AD) from controls."
They analyzed serum protein–based biomarker data from 197 patients diagnosed with AD and compared it them 203 normal controls. The statistical analyses they used to create a biomarker risk score included a number of analytes that can be linked to insulin resistance and inflammation, including fibrinogen, interleukin-10, and C-reactive protein. When the numbers were crunched their biomarker risk score was highly accurate:
"The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD [identified 80% with AD, excluded 91% without]. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94 [94%}, 0.84 [84%], and 0.95, respectively."
This is very valuable because other proposed tests involve lumbar puncture for cerebrospinal fluid or expensive neuorimaging, both with obvious drawbacks. The authors' conclusion also highlights the importance of inflammation (vascular and otherwise, associated with insulin resistance) in the development of AD:
"These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses...suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients."