P2-185: IMPROVED QUANTIFICATION METHODS FOR BRAIN β-AMYLOID BURDEN ON 11C-PIB PET IN PATIENTS WITH ALZHEIMER'S DISEASE

: Alzheimer’s Disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezilrelated compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

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Sildenafil restores cognitive function without affecting β-amyloid burden in a mouse model of Alzheimer's disease

British Journal of Pharmacology ◽

10.1111/j.1476-5381.2011.01517.x ◽

2011 ◽

Vol 164 (8) ◽

pp. 2029-2041 ◽

Cited By ~ 100

Author(s):

M Cuadrado-Tejedor ◽

I Hervias ◽

A Ricobaraza ◽

E Puerta ◽

JM Pérez-Roldán ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Mouse Model ◽

Amyloid Burden ◽

Model Of Alzheimer’S Disease ◽

Β Amyloid

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Possible Involvement of Transthyretin in Hippocampal β-Amyloid Burden and Learning Behaviors in a Mouse Model of Alzheimer’s Disease (TgCRND8)

Neurodegenerative Diseases ◽

10.1159/000285513 ◽

2010 ◽

Vol 7 (1-3) ◽

pp. 88-95 ◽

Cited By ~ 6

Author(s):

Sihem Doggui ◽

Jonathan Brouillette ◽

Jean-Guy Chabot ◽

Mark Farso ◽

Rémi Quirion

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Amyloid Burden ◽

Learning Behaviors ◽

Model Of Alzheimer’S Disease ◽

Β Amyloid

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Mild behavioral impairment correlates of cognitive impairments in older adults without dementia: mediation by amyloid pathology

Translational Psychiatry ◽

10.1038/s41398-021-01675-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yan Sun ◽

Wei Xu ◽

Ke-Liang Chen ◽

Xue-Ning Shen ◽

Lan Tan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairments ◽

Amyloid Pet ◽

Amyloid Burden ◽

Behavioral Impairment ◽

Mediation Effects ◽

Mediation Analyses ◽

Language Functions ◽

Β Amyloid

AbstractThe relationship between mild behavioral impairment (MBI) and Alzheimer’s disease (AD) is intricate and still not well investigated. The purpose of the study is to examine the roles of the AD imaging pathologies in modulating the associations of MBI with cognitive impairments. We analyzed 1129 participants (563 [49.86%] female), who had measures of Neuropsychiatric Inventory Questionnaire (NPI-Q), cognition, and amyloid PET AD biomarkers from the Alzheimer’s disease Neuroimaging Initiative (ADNI). We assess the longitudinal neuropathological and clinical correlates of baseline MBI via linear mixed effects and Cox proportional hazard models. The mediation analyses were used to test the mediation effects of AD pathologies on cognition. We found that MBI was associated with worse global cognition as represented by Mini-Mental State Examination (MMSE) (p < 0.001), and higher β-amyloid burden (p < 0.001). β-amyloid partially mediated the effects of MBI on cognition with the mediation percentage varied from 14.67 to 40.86% for general cognition, memory, executive, and language functions for non-dementia individuals. However, no significant associations were discovered between MBI and tau burden or neurodegeneration. Furthermore, longitudinal analyses revealed that individuals with MBI had a faster increase in brain amyloid burden (p < 0.001) and a higher risk of clinical conversion (HR = 2.42, 95% CI = 1.45 to 4.01 p < 0.001). In conclusion, MBI could be an imperative prediction indicator of clinical and pathological progression. In addition, amyloid pathologies might partially mediate the influences of MBI on cognitive impairments and AD risk.

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Modulation of glucose metabolism and metabolic connectivity by β-amyloid

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16654492 ◽

2016 ◽

Vol 36 (12) ◽

pp. 2058-2071 ◽

Cited By ~ 9

Author(s):

Felix Carbonell ◽

Alex P Zijdenbos ◽

Donald G McLaren ◽

Yasser Iturria-Medina ◽

Barry J Bedell ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Disease Process ◽

Continuous Variable ◽

Amyloid Burden ◽

Early Stages ◽

Metabolic Connectivity ◽

Β Amyloid ◽

Glucose Hypometabolism

Glucose hypometabolism in the pre-clinical stage of Alzheimer’s disease (AD) has been primarily associated with the APOE ɛ4 genotype, rather than fibrillar β-amyloid. In contrast, aberrant patterns of metabolic connectivity are more strongly related to β-amyloid burden than APOE ɛ4 status. A major limitation of previous studies has been the dichotomous classification of subjects as amyloid-positive or amyloid-negative. Dichotomous treatment of a continuous variable, such as β-amyloid, potentially obscures the true relationship with metabolism and reduces the power to detect significant changes in connectivity. In the present work, we assessed alterations of glucose metabolism and metabolic connectivity as continuous function of β-amyloid burden using positron emission tomography scans from the Alzheimer’s Disease Neuroimaging Initiative study. Modeling β-amyloid as a continuous variable resulted in better model fits and improved power compared to the dichotomous model. Using this continuous model, we found that both APOE ɛ4 genotype and β-amyloid burden are strongly associated with glucose hypometabolism at early stages of Alzheimer’s disease. We also determined that the cumulative effects of β-amyloid deposition result in a particular pattern of altered metabolic connectivity, which is characterized by global, synchronized hypometabolism at early stages of the disease process, followed by regionally heterogeneous, progressive hypometabolism.

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