Your search for: 'author:("de Leon, Mony")' has returned 15 results. (0.017s) Save search

Authors: Glodzik, Lidia | Randall, Catherine | Rusinek, Henry | de Leon, Mony J.

Article Type: Review Article

Abstract: There is growing evidence that cerebrovascular reactivity to carbon dioxide (CVRCO2 ) is impaired in Alzheimer's disease (AD). Preclinical and animal studies suggest chronic hypercontractility in brain vessels in AD. We review (a) preclinical studies of mechanisms for impaired CVRCO2 in AD; (b) clinical studies of cerebrovascular function in subjects with AD dementia, mild cognitive impairment (MCI), and normal cognition. Although results of clinical studies are inconclusive, an increasing number of reports reveal an impairment of vascular reactivity to carbon dioxide in subjects with AD, and possibly also in MCI. Thus, CVRCO2 may be an attractive means to detect an …early vascular dysfunction in subjects at risk. Show more

Keywords: Alzheimer's disease, carbon dioxide, cognitive impairment, vascular, vasoreactivity

DOI: 10.3233/JAD-122011

Citation: Journal of Alzheimer's Disease, vol. 35, no. 3, pp. 427-440, 2013

Authors: Swerdlow, Russell H. | de Leon, Mony J. | Marcus, David L.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) features perturbed brain glucose utilization, which could contribute to brain bioenergetic failure. This led some to consider using ketone bodies to enhance AD brain bioenergetics and treat AD. Objective: We evaluated the rate at which brain homogenates from persons with Alzheimer’s disease (AD) metabolize D-β-hydroxybutyrate (BHB). Methods: We homogenized pieces of temporal cortex from frozen autopsy brains obtained from recently deceased AD subjects (n  = 4), and age-matched subjects that did not have clinical AD (n  = 3). Measuring the rate of CO2 production that followed the introduction of radiolabeled BHB to the homogenates yielded a BHB utilization …rate. Results: Compared to the control homogenates, the BHB-supported CO2 production rate was 66%lower in the AD homogenates (p  < 0.05). Conclusions: AD brains can utilize BHB, albeit less robustly than control brains. In conjunction with a previous study that demonstrated reduced glucose utilization in AD brain homogenates, our BHB data provide further evidence of AD brain mitochondrial dysfunction or altered mitochondrial biology. Show more

Keywords: Alzheimer’s disease, betahydroxybutyrate, ketone body, metabolism, mitochondria

DOI: 10.3233/ADR-210002

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 135-141, 2021

Authors: Mosconi, Lisa | Berti, Valentina | Glodzik, Lidia | Pupi, Alberto | De Santi, Susan | de Leon, Mony J.

Article Type: Review Article

Abstract: The development of prevention therapies for Alzheimer's disease (AD) would greatly benefit from biomarkers that are sensitive to subtle brain changes occurring in the preclinical stage of the disease. Early diagnostics is necessary to identify and treat at risk individuals before irreversible neuronal loss occurs. In vivo imaging has long been used to evaluate brain structural and functional abnormalities as predictors of future AD in non-demented persons. Prior to development of amyloid-β (Aβ) tracers for positron emission tomography (PET), the most widely utilized PET tracer in AD was 2-[18F]fluoro-2-Deoxy-D-glucose (FDG) PET. For over 20 years, FDG-PET has been used to …measure cerebral metabolic rates of glucose (CMRglc), a proxy for neuronal activity, in AD. Many studies have shown that CMRglc reductions occur early in AD, correlate with disease progression, and predict histopathological diagnosis. This paper reviews reports of clinical and preclinical CMRglc reductions observed in association with genetic and non-genetic risk factors for AD. We then briefly review brain Aβ PET imaging studies in AD and discuss the potential of combining symptoms-sensitive FDG-PET measures with pathology-specific Aβ-PET to improve the early detection of AD. Show more

Keywords: Amyloid-β, cerebral metabolic rate of glucose (CMRglc), normal aging, positron emission tomography, preclinical detection

DOI: 10.3233/JAD-2010-091504

Citation: Journal of Alzheimer's Disease, vol. 20, no. 3, pp. 843-854, 2010

Authors: Mosconi, Lisa | de Leon, Mony | Murray, John | E, Lezi | Lu, Jianghua | Javier, Elizabeth | McHugh, Pauline | Swerdlow, Russell H.

Article Type: Research Article

Abstract: Biomarker studies demonstrate inheritance of glucose hypometabolism and increased amyloid-β deposition in adult offspring of mothers, but not fathers, affected by late-onset Alzheimer's disease (LOAD). The underlying genetic mechanisms are unknown. We investigated whether cognitively normal (NL) individuals with a maternal history of LOAD (MH) have reduced platelet mitochondrial cytochrome oxidase activity (COX, electron transport chain complex IV) compared to those with paternal (PH) or negative family history (NH). Thirty-six consecutive NL individuals (age 55 ± 15 y, range 27–71 y, 56% female, CDR = 0, MMSE ≥28, 28% APOE-4 carriers), including 12 NH, 12 PH, and 12 MH, received …a blood draw to measure platelet mitochondrial COX activity. Citrate synthase activity (CS) was measured as a reference. Groups were comparable for clinical and neuropsychological measures. We found that after correcting for CS, COX activity was reduced by 29% in MH compared to NH, and by 30% in MH compared to PH (p ≤ 0.006). Results remained significant controlling for age, gender, education, and APOE. No differences were found between PH and NH. COX measures discriminated MH from the other groups with accuracy ≥75%, and relative risk ≥3 (p ≤ 0.005). Among NL with LOAD-parents, only those with MH showed reduced COX activity in platelet mitochondria compared to PH and NH. The association between maternal history of LOAD and systemic COX reductions suggests transmission via mitochondrial DNA, which is exclusively maternally inherited in humans. Show more

Keywords: Early diagnosis, electron transport complex IV, late onset Alzheimer's disease, mitochondria

DOI: 10.3233/JAD-2011-110866

Citation: Journal of Alzheimer's Disease, vol. 27, no. 3, pp. 483-490, 2011

Authors: Kamer, Angela R. | Dasanayake, Ananda P. | Craig, Ronald G. | Glodzik-Sobanska, Lidia | Bry, Miroslow | de Leon, Mony J.

Article Type: Review Article

Abstract: Alzheimer's disease (AD) affects approximately 4.5 million people in the U.S. and this number will increase as the population ages and the life-span increases. Therefore, of paramount importance is identifying mechanisms and factors that affect the risk of developing AD. The etiology and pathogenic mechanisms for AD have not been defined, although inflammation within the brain is thought to play a role. Consistent with this hypothesis, studies suggest that peripheral infections contribute to the inflammatory state of the central nervous system. Periodontitis is a prevalent, persistent peripheral infection associated with gram negative, anaerobic bacteria that are capable of exhibiting localized …and systemic infections in the host. This review offers a hypothetical link between periodontitis and AD and will present possible mechanistic links between periodontitis related inflammation and AD. It will review the pathogenesis of periodontitis and the mechanisms by which periodontal infections may affect the onset and progression of AD. Since periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD. Show more

Keywords: Alzheimer's disease, cytokines, periodontal bacteria, periodontitis, peripheral infection

DOI: 10.3233/JAD-2008-13408

Citation: Journal of Alzheimer's Disease, vol. 13, no. 4, pp. 437-449, 2008

Authors: Kim, Hee-Jin | Im, Hyung Kyun | Kim, Juhan | Han, Jee-young | de Leon, Mony | Deshpande, Anup | Moon, Won-Jin

Article Type: Research Article

Abstract: Background: Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. Objective: We investigated that dementia with RBD might show distinctive cortical atrophic patterns. Methods: A total of 31 patients with idiopathic Parkinson’s disease (IPD), 23 with clinically probable Alzheimer’s disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for …detection of regional brain atrophy among groups of subjects. Results: Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. Conclusion: The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α -synucleinopathy. Show more

Keywords: Brain atrophy, dementia, RBD screening questionnaire, REM sleep disorder, voxel-based morphometry

DOI: 10.3233/JAD-151197

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1101-1109, 2016

Authors: Glodzik, Lidia | De Santi, Susan | Rich, Kenneth E. | Brys, Miroslaw | Pirraglia, Elizabeth | Mistur, Rachel | Switalski, Remigiusz | Mosconi, Lisa | Sadowski, Martin | Zetterberg, Henrik | Blennow, Kaj | de Leon, Mony J.

Article Type: Short Communication

Abstract: Previous studies showed that memantine inhibits tau hyperphosphorylation in vitro. In this study, phosphorylated tau (P-tau) and total tau (T-tau) were measured before and after 6 month treatment with memantine in 12 subjects ranging from normal cognition with subjective memory complaints, through mild cognitive impairment to mild Alzheimer's disease. Thirteen non-treated individuals served as controls. Treatment was associated with a reduction of P-tau in subjects with normal cognition. No treatment effects were seen among impaired individuals, suggesting that longer treatment time may be necessary to achieve biomarker effect in this group.

Keywords: Alzheimer's disease, biomarkers, cerebrospinal fluid, memantine, phosphorylated tau, total tau

DOI: 10.3233/JAD-2009-1183

Citation: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 509-513, 2009

Authors: Wegiel, Jerzy | Bobinski, Maciej | Tarnawski, Michal | Dziewiatkowski, Jerzy | Popovitch, Eirene | Bobinski, Margaret | Lach, Boleslaw | Reisberg, Barry | Miller, Douglas C. | de Santi, Susan | de Leon, Mony J.

Article Type: Research Article

Abstract: A morphometric study of amyloid-ß-positive plaques in the neocortex of eight non-demented people from 68 to 82 years of age and 17 subjects with late-stage Alzheimer disease (GDS stage 7/FAST stages 7a–f) from 73 to 93 years of age shows a shift from prevalence of fibrillar plaques to prevalence of nonfibrillar plaques. In the aged, non-demented subjects, about 4/mm2 plaques are detectable in the neocortex, and the majority are fibrillar plaques. Specifically, 64% found to be classical fibrillar and Thioflavin-S-positive bright primitive plaques. A lower percentage of pale primitive plaques (35%) relatively small proportion of plaques that are poor in …thioflavin S-positive fibrils. The numerical density of plaques in the severe stage of AD increases to about 41/mm2 . Severely demented subjects appear to maintain an active process of fibrillar plaque formation. This is reflected in the presence of 3% bright primitive plaques. Severely demented subjects also manifest plaque degradation, reflected in the presence of 22% and 48% percentages of classical fibrillar plaques in non-demented subjects and in the end stage of disease suggest that once activated, the process of fibrillar plaque formation persists at a somewhat stable rate during the whole course of brain amyloidosis. Show more

Keywords: Alzheimer disease, diffuse plaques, fibrillar plaques, morphometry

DOI: 10.3233/JAD-2001-3108

Citation: Journal of Alzheimer's Disease, vol. 3, no. 1, pp. 49-57, 2001

Authors: Brys, Miroslaw | Glodzik, Lidia | Mosconi, Lisa | Switalski, Remigiusz | De Santi, Susan | Pirraglia, Elizabeth | Rich, Kenneth | Kim, Byeong C. | Mehta, Pankaj | Zinkowski, Ray | Pratico, Domenico | Wallin, Anders | Zetterberg, Henrik | Tsui, Wai H. | Rusinek, Henry | Blennow, Kaj | de Leon, Mony J.

Article Type: Research Article

Abstract: Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years. CSF measures included total and phosphorylated tau (T-tau, P-tau231 ), amyloid-β (Aβ42 /Aβ40 ) and isoprostane. Voxel-based morphometry identified gray matter concentration (GMC) differences best distinguishing study groups and individual GMC values were calculated. Rate …of medial temporal lobe (MTL) atrophy was examined using regional boundary shift (rBS) method. At baseline, for MRI, MCI-AD showed reduced GMC-MTL, and for CSF higher CSF T-tau, P-tau231 , IP and lower Aβ42 /Aβ40 as compared with MCI-MCI or NL-NL. Longitudinally, rBS-MTL atrophy was higher in MCI-AD than in either MCI-MCI or NL-NL, particularly in the left hemisphere. CSF data showed longitudinally greater increases of isoprostane in MCI-AD as compared with NL-NL. Combining baseline CSF-P-tau231 and GMC-MTL significantly increased overall prediction of AD from 74% to 84% (pstep < 0.05). These results provide support for including multiple modalities of biomarkers in the identification of memory clinic patients at increased risk for dementia. Show more

Keywords: Alzheimer's disease, brain atrophy, cerebrospinal fluid biomarkers, early diagnosis

DOI: 10.3233/JAD-2009-0968

Citation: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 351-362, 2009

Authors: Ozsahin, Ilker | Zhou, Liangdong | Wang, Xiuyuan | Garetti, Jacob | Jamison, Keith | Xi, Ke | Tanzi, Emily | Jaywant, Abhishek | Patchell, Abigail | Maloney, Thomas | de Leon, Mony J. | Kuceyeski, Amy | Shah, Sudhin A. | Li, Yi | Butler, Tracy A.

Article Type: Short Communication

Abstract: Diffusion tensor imaging along perivascular spaces (DTI-ALPS) is a novel MRI method for assessing brain interstitial fluid dynamics, potentially indexing glymphatic function. Failed glymphatic clearance is implicated in Alzheimer’s disease (AD) pathophysiology. We assessed the contribution of age and female sex (strong AD risk factors) to DTI-ALPS index in healthy subjects. We also for the first time assessed the effect of head size. In accord with prior studies, we show reduced DTI-ALPS index with aging, and in men compared to women. However, head size may be a major contributing factor to this counterintuitive sex difference.

Keywords: Aging, Alzheimer’s disease, DTI-ALPS, glymphatic system, interstitial fluid dynamics, sex difference

DOI: 10.3233/ADR-230143

Citation: Journal of Alzheimer's Disease Reports, vol. 8, no. 1, pp. 355-361, 2024