Neuro-degeneration profile of Alzheimer's patients: A brain morphometry study

Abstract

IntroductionAlzheimer's disease (AD) is a primary and progressive neurodegenerative disorder, which is marked by cognitive deterioration and memory impairment. Atrophy of hippocampus and other basal brain regions is one of the most predominant structural imaging findings related to AD. Most studies have evaluated the pre-clinical and initial stages of AD through clinical trials using Magnetic Resonance Imaging. Structural biomarkers for advanced AD stages have not been evaluated yet, being considered only hypothetically.ObjectiveTo evaluate the brain morphometry of AD patients at all disease stages, identifying the structural neuro-degeneration profile associated with AD severity.Material and methodsAD patients aged 60 years or over at different AD stages were recruited and grouped into three groups following the Clinical Dementia Rating (CDR) score: CDR1 (n = 16), CDR2 (n = 15), CDR3 (n = 13). Age paired healthy volunteers (n = 16) were also recruited (control group). Brain images were acquired on a 3T magnetic resonance scanner using a conventional Gradient eco 3D T1-w sequence without contrast injection. Volumetric quantitative data and cortical thickness were obtained by automatic segmentation using the Freesurfer software. Volume of each brain region was normalized by the whole brain volume in order to minimize age and body size effects. Volume and cortical thickness variations among groups were compared.ResultsAtrophy was observed in the hippocampus, amygdala, entorhinal cortex, parahippocampal region, temporal pole and temporal lobe of patients suffering from AD at any stage. Cortical thickness was reduced only in the parahippocampal gyrus at all disease stages. Volume and cortical thickness were correlated with the Mini Mental State Examination (MMSE) score in all studied regions, as well as with CDR and disease duration.Discussion and conclusionAs previously reported, brain regions affected by AD during its initial stages, such as hippocampus, amygdala, entorhinal cortex, and parahippocampal region, were found to be altered even in individuals with severe AD. In addition, individuals, specifically, with CDR 3, have multiple regions with lower volumes than individuals with a CDR 2. These results indicate that rates of atrophy have not plateaued out at CDR 2–3, and in severe patients there are yet neuronal loss and gliosis. These findings can add important information to the more accepted model in the literature that focuses mainly on early stages. Our findings allow a better understanding on the AD pathophysiologic process and follow-up process of drug treatment even at advanced disease stages.

Progression of Alzheimer's disease and effect of scFv‐h3D6 immunotherapy in the 3xTg‐AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy

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“…In this study, different MRI/MRS parameters were analyzed at 5, 7, 9, and 12‐mo. MRI was used to determine the volume of different cerebral regions involved in the disease, as a reduction in cerebral volume is associated with atrophy and neurodegeneration due to neuron loss in humans and mice . We have also quantified the T 2 value, whose changes are associated with the appearance of amyloid plaques, neuroinflammation, and neurodegeneration .…”

Grafted human pluripotent stem cell-derived cortical neurons integrate into adult human cortical neural circuitry

“…Brain injury, stroke, epilepsy, and chronic neurodegenerative disorders such as Alzheimer's disease and amyotrophic lateral sclerosis are associated with loss or dysfunction of cortical neurons, leading to motor, sensory, and cognitive deficits. [1][2][3][4] Effective treatments to restore function are lacking. Novel strategies to replace the lost neurons and reestablish their afferent and efferent connections in order to reconstruct damaged neural circuitries are highly warranted.…”

Inter-scanner reproducibility of brain volumetry: influence of automated brain segmentation software

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