Journal of Alzheimer's Disease - Volume 89, issue 4

Authors: Wright, Joy R. | Deen, Quazi Fahm E. | Stevenson, Anna | Telford-Cooke, Leolie L. | Parker, Craig | Martin-Ruiz, Carmen | Steinert, Joern R. | Kalaria, Raj N. | Mukaetova-Ladinska, Elizabeta B.

Article Type: Research Article

Abstract: Background: Myeloperoxidase (MPO), a neutrophil-derived pro-inflammatory protein, co-localizes with amyloid-β (Aβ) plaques in Alzheimer’s disease (AD). Anti-dementia treatment may facilitate efflux of Aβ and associated plaque proteins from the brain to the peripheral circulation, therefore providing potential biomarkers for the monitoring of donor response to drug treatment. Objective: We investigated the diagnostic utility of MPO as a biomarker of AD, and how anti-dementia treatment alters plasma MPO concentration. Methods: Thirty-two AD patients were recruited, and plasma collected pre-drug administration (baseline), and 1- and 6-months post-treatment. All patients received cholinesterase inhibitors (ChEIs). At baseline and 6 months, …patients underwent neuropsychological assessment. Forty-nine elderly healthy individuals with normal cognitive status served as controls. Plasma MPO concentration was measured by ELISA. Results: AD drug naïve patients had similar plasma MPO concentration to their control counterparts (p  > 0.05). Baseline MPO levels positively correlated with Neuropsychiatric Inventory score (r  = 0.5080; p  = 0.011) and carer distress (r  = 0.5022; p  = 0.012). Following 1-month ChEI treatment, 84.4% of AD patients exhibited increased plasma MPO levels (p  < 0.001), which decreased at 6 months (p  < 0.001). MPO concentration at 1 month was greatest in AD patients whose memory deteriorated during the study period (p  = 0.028), and for AD patients with deterioration in Cornell assessment score (p  = 0.044). Conclusion: Whereas baseline MPO levels did not differentiate between healthy and AD populations, baseline MPO positively correlated with initial Neuropsychiatric Inventory evaluation. Post-treatment, transient MPO upregulation in ChEI-treated patients may reflect worse therapeutic outcome. Further studies are required to assess the potential of plasma MPO as an AD therapeutic biomarker. Show more

Keywords: Alzheimer’s disease, biomarkers, cholinesterase inhibitors, inflammation, myeloperoxidase, plasma

DOI: 10.3233/JAD-220642

Citation: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1483-1492, 2022

Authors: Beheshti, Iman | Geddert, Natasha | Perron, Jarrad | Gupta, Vinay | Albensi, Benedict C. | Ko, Ji Hyun

Article Type: Research Article

Abstract: Background: We previously introduced a machine learning-based Alzheimer’s Disease Designation (MAD) framework for identifying AD-related metabolic patterns among neurodegenerative subjects. Objective: We sought to assess the efficiency of our MAD framework for tracing the longitudinal brain metabolic changes in the prodromal stage of AD. Methods: MAD produces subject scores using five different machine-learning algorithms, which include a general linear model (GLM), two different approaches of scaled subprofile modeling, and two different approaches of a support vector machine. We used our pre-trained MAD framework, which was trained based on metabolic brain features of 94 patients with AD …and 111 age-matched cognitively healthy (CH) individuals. The MAD framework was applied on longitudinal independent test sets including 54 CHs, 51 stable mild cognitive impairment (sMCI), and 39 prodromal AD (pAD) patients at the time of the clinical diagnosis of AD, and two years prior. Results: The GLM showed excellent performance with area under curve (AUC) of 0.96 in distinguishing sMCI from pAD patients at two years prior to the time of the clinical diagnosis of AD while other methods showed moderate performance (AUC: 0.7–0.8). Significant annual increment of MAD scores were identified using all five algorithms in pAD especially when it got closer to the time of diagnosis (p  < 0.001), but not in sMCI. The increased MAD scores were also significantly associated with cognitive decline measured by Mini-Mental State Examination in pAD (q  < 0.01). Conclusion: These results suggest that MAD may be a relevant tool for monitoring disease progression in the prodromal stage of AD. Show more

Keywords: Alzheimer’s disease, brain metabolism, FDG PET, machine learning

DOI: 10.3233/JAD-220585

Citation: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1493-1502, 2022

Authors: George, Daniel R.

Article Type: Book Review

DOI: 10.3233/JAD-220791

Citation: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1503-1505, 2022