Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers

Honea, Robyn A.; John, Casey S.; Green, Zachary D.; Kueck, Paul J.; Taylor, Matthew; Lepping, Rebecca J.; Townley, Ryan A.; Vidoni, Eric D.; Burns, JM; Morris, Jill K.

doi:10.1002/trc2.12239

Cited by 11 publications

(12 citation statements)

References 54 publications

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“…Elevated glucose, insulin resistance, and type 2 diabetes induce chronic inflammation and oxidative stress and are increasingly linked to elevated risk for AD ( Khan and Hegde, 2020 ). Human studies suggest that consuming a high glycemic diet ( Taylor et al, 2017 , 2021 ) and worsening glucoregulation ( Morris et al, 2016 ; Gomez et al, 2018 ; Honea et al, 2022 ) are related to increased Aβ burden in cognitively normal older adults, even in those without diabetes. Individuals with diabetes that have higher peripheral fasting glucose levels also have higher brain glucose levels, which is suggested to alter brain Aβ processing and clearance ( Heikkila et al, 2009 ; Madhusudhanan et al, 2020 ).…”

Section: Ketotherapies and Amyloid-βmentioning

confidence: 99%

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease (AD) is a progressive neurodegenerative condition characterized by clinical decline in memory and other cognitive functions. A classic AD neuropathological hallmark includes the accumulation of amyloid-β (Aβ) plaques, which may precede onset of clinical symptoms by over a decade. Efforts to prevent or treat AD frequently emphasize decreasing Aβ through various mechanisms, but such approaches have yet to establish compelling interventions. It is still not understood exactly why Aβ accumulates in AD, but it is hypothesized that Aβ and other downstream pathological events are a result of impaired bioenergetics, which can also manifest prior to cognitive decline. Evidence suggests that individuals with AD and at high risk for AD have functional brain ketone metabolism and ketotherapies (KTs), dietary approaches that produce ketone bodies for energy metabolism, may affect AD pathology by targeting impaired brain bioenergetics. Cognitively normal individuals with elevated brain Aβ, deemed “preclinical AD,” and older adults with peripheral metabolic impairments are ideal candidates to test whether KTs modulate AD biology as they have impaired mitochondrial function, perturbed brain glucose metabolism, and elevated risk for rapid Aβ accumulation and symptomatic AD. Here, we discuss the link between brain bioenergetics and Aβ, as well as the potential for KTs to influence AD risk and progression.

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Section: Ketotherapies and Amyloid-βmentioning

confidence: 99%

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

et al. 2022

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“…Meanwhile, our MVMR results revealed that the causal effect of OCN on AD was also partially dependent of glucose metabolism, especially for FG. Numerous studies have showed that impaired FG was related to increased cerebral beta-amyloid accumulation and atrophy, and associated with a higher risk of AD [ 67 , 68 ]. It is reported that the levels of glucose transporter-3 in AD patients were decreased, leading to impaired glycolytic flux, which was related to the severity of AD pathology [ 69 ].…”

Section: Discussionmentioning

confidence: 99%

Causal effect of blood osteocalcin on the risk of Alzheimer’s disease and the mediating role of energy metabolism

Guo,

Yang,

Zhou

et al. 2024

Transl Psychiatry

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Growing evidence suggests an association between osteocalcin (OCN), a peptide derived from bone and involved in regulating glucose and lipid metabolism, and the risk of Alzheimer’s disease (AD). However, the causality of these associations and the underlying mechanisms remain uncertain. We utilized a Mendelian randomization (MR) approach to investigate the causal effects of blood OCN levels on AD and to assess the potential involvement of glucose and lipid metabolism. Independent instrumental variables strongly associated (P < 5E-08) with blood OCN levels were obtained from three independent genome-wide association studies (GWAS) on the human blood proteome (N = 3301 to 35,892). Two distinct summary statistics datasets on AD from the International Genomics of Alzheimer’s Project (IGAP, N = 63,926) and a recent study including familial-proxy AD patients (FPAD, N = 472,868) were used. Summary-level data for fasting glucose (FG), 2h-glucose post-challenge, fasting insulin, HbA1c, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol (TC), and triglycerides were incorporated to evaluate the potential role of glucose and lipid metabolism in mediating the impact of OCN on AD risk. Our findings consistently demonstrate a significantly negative correlation between genetically determined blood OCN levels and the risk of AD (IGAP: odds ratio [OR, 95%CI] = 0.83[0.72–0.96], P = 0.013; FPAD: OR = 0.81 [0.70–0.93], P = 0.002). Similar estimates with the same trend direction were obtained using other statistical approaches. Furthermore, employing multivariable MR analysis, we found that the causal relationship between OCN levels and AD was disappeared after adjustment of FG and TC (IGAP: OR = 0.97[0.80–1.17], P = 0.753; FPAD: OR = 0.98 [0.84–1.15], P = 0.831). There were no apparent instances of horizontal pleiotropy, and leave-one-out analysis showed good stability of the estimates. Our study provides evidence supporting a protective effect of blood OCN levels on AD, which is primarily mediated through regulating FG and TC levels. Further studies are warranted to elucidate the underlying physio-pathological mechanisms.

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“…The DTI data were analyzed using FSL 6.1 software. Data processing steps included eddy current & motion correction applying the FDT tool, brain extraction applying the BET tool, and DTI measure reconstruction applying the DTI-FIT tool ( Honea et al, 2022 ). Additionally, to evaluate the microstructural changes in white matter, the fractional anisotropy (FA) and mean diffusivity (MD) values based on WMH and NAWM mask were extracted employing Matlab code, which are widely used to evaluate the microstructural integrity of white matter fibers.…”

Section: Methodsmentioning

confidence: 99%

Unraveling the link: white matter damage, gray matter atrophy and memory impairment in patients with subcortical ischemic vascular disease

Huang,

Cheng,

Liu

et al. 2024

Front. Neurosci.

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IntroductionPrior MRI studies have shown that patients with subcortical ischemic vascular disease (SIVD) exhibited white matter damage, gray matter atrophy and memory impairment, but the specific characteristics and interrelationships of these abnormal changes have not been fully elucidated.Materials and methodsWe collected the MRI data and memory scores from 29 SIVD patients with cognitive impairment (SIVD-CI), 29 SIVD patients with cognitive unimpaired (SIVD-CU) and 32 normal controls (NC). Subsequently, the thicknesses and volumes of the gray matter regions that are closely related to memory function were automatically assessed using FreeSurfer software. Then, the volume, fractional anisotropy (FA), mean diffusivity (MD), amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of white matter hyperintensity (WMH) region and normal-appearing white matter (NAWM) were obtained using SPM, DPARSF, and FSL software. Finally, the analysis of covariance, spearman correlation and mediation analysis were used to analyze data.ResultsCompared with NC group, patients in SIVD-CI and SIVD-CU groups showed significantly abnormal volume, FA, MD, ALFF, and ReHo values of WMH region and NAWM, as well as significantly decreased volume and thickness values of gray matter regions, mainly including thalamus, middle temporal gyrus and hippocampal subfields such as cornu ammonis (CA) 1. These abnormal changes were significantly correlated with decreased visual, auditory and working memory scores. Compared with the SIVD-CU group, the significant reductions of the left CA2/3, right amygdala, right parasubiculum and NAWM volumes and the significant increases of the MD values in the WMH region and NAWM were found in the SIVD-CI group. And the increased MD values were significantly related to working memory scores. Moreover, the decreased CA1 and thalamus volumes mediated the correlations between the abnormal microstructure indicators in WMH region and the decreased memory scores in the SIVD-CI group.ConclusionPatients with SIVD had structural and functional damages in both WMH and NAWM, along with specific gray matter atrophy, which were closely related to memory impairment, especially CA1 atrophy and thalamic atrophy. More importantly, the volumes of some temporomesial regions and the MD values of WMH regions and NAWM may be potentially helpful neuroimaging indicators for distinguishing between SIVD-CI and SIVD-CU patients.

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Relationship of fasting glucose and longitudinal Alzheimer's disease imaging markers

Cited by 11 publications

References 54 publications

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

Potential for Ketotherapies as Amyloid-Regulating Treatment in Individuals at Risk for Alzheimer’s Disease

Causal effect of blood osteocalcin on the risk of Alzheimer’s disease and the mediating role of energy metabolism

Unraveling the link: white matter damage, gray matter atrophy and memory impairment in patients with subcortical ischemic vascular disease

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