Relationships between hippocampal microstructure, metabolism, and function in early Alzheimer’s disease

Abstract

Abnormal microstructural integrity and glucose metabolism of the hippocampus are common in subjects with Alzheimer's disease (AD) that typically manifest as episodic memory impairment. The above-tissue alterations can be captured in vivo using diffusion tensor imaging (DTI) and positron emission tomography with [18F]fluorodeoxyglucose (FDG-PET). Here, we explored relationships between the above neuroimaging and cognitive markers of early AD-specific hippocampal damage. Twenty patients with early AD (MMSE 25.7 ± 1.7) were studied using DTI and FDG-PET. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). In the between-modality correlation analysis, FDG uptake was strongly associated with diffusivity in the left anterior hippocampus only (r = -0.81, p < 0.05 Bonferroni's corrected for multiple tests). Performance on DVR significantly correlated with left anterior (r = -0.80, p < 0.05) and left mean (r = -0.72, p < 0.05) hippocampal diffusivity, while the correlation with left anterior FDG uptake did not reach statistical significance (r = 0.52, n.s.). DTI-derived diffusivity of the anterior hippocampus might be a sensitive early marker of hippocampal dysfunction as reflected at the synaptic and cognitive levels. This neurobiological distinction of the anterior hippocampus might be related to the disruption of the perforant pathway that is known to occur early in the course of AD.

Repeated Mild Traumatic Brain Injury: Mechanisms of Cerebral Vulnerability

“…In multiple sclerosis patient who exhibit demyelinated axons also shown remote effects on CMRglc with significant glucose metabolic depression in the thalamus and cerebellum (Derache et al, 2006). This type of denervation induced CMRglc decrease has also been reported in Alzhiemer's disease (Yakushev et al, 2011). Damage to axons and or decreases in synaptic connectivity can directly affect cerebral activity levels, CMRglc and behavioral outcome (Browne et al, 2001).…”

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging

“…Our study could not find significant difference in FA maps between groups. Previous reports of FA abnormalities in mild AD have predominantly employed Region Of Interest (ROI) based approaches, as opposed to our whole‐brain voxel‐wise approach (Yakushev et al ., ; Nowrangi et al ., ; Tighe et al ., ). To the best of our knowledge, there has been only one study by Bosch et al ., reporting reduction in FA among mild AD using voxel wise whole brain white matter tract comparisons; however, the results reported in this study were unadjusted for age and gender variations (Bosch et al ., ).…”

A review of β-amyloid neuroimaging in Alzheimer's disease

“…Diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping and diffusion tensor imaging (DTI) has been used to investigate the white matter changes in areas such as the temporal lobe, hippocampus and corpus callosum (Ramani et al, 2006; Small et al, 2008; Stebbins and Murphy, 2009). In particular, DTI is capable of assessing microstructural and connective changes in the hippocampus and its related structures, arising from neuronal loss and axonal degeneration (Yakushev et al, 2011a,b; Hattori et al, 2012). Alternatively, magnetization transfer imaging (MTI) is able to detect structural damage as a reduction in the magnetization transfer rate (MTR) reflects decreased tissue homogeneity from pathological changes such as neuronal loss and gliosis in gray matter, and demyelination and axonal loss in white matter (Glodzik-Sobanska et al, 2005; Ramani et al, 2006).…”

“…Axonal degeneration and white matter changes that occur secondary to neuronal loss can be investigated with DTI. Yukashev and colleagues demonstrated that both macroscopic changes shown by volumetric analysis and microstructural changes revealed by DTI lead to metabolic changes in the posterior cingulate cortex (Yakushev et al, 2011a,b). Hattori et al (2012) utilized DTI to analyse the fornix, which contains efferent fibers from the hippocampus, in AD patients and patients with normal pressure hydrocephalus (NPH) which is another cause of progressive dementia.…”