Journal of Alzheimer's Disease - Volume 93, issue 2

Authors: Xiao, Yaqiong | Liao, Liangjun | Huang, Kaiyu | Yao, Shun | Gao, Lei

Article Type: Research Article

Abstract: Background: Hippocampal atrophy is a significant brain marker of pathology in Alzheimer’s disease (AD). The hippocampal parenchymal fraction (HPF) was recently developed to better assess the hippocampal volumetric integrity, and it has been shown to be a sensitive measure of hippocampal atrophy in AD. Objective: To investigate the clinical relevance of hippocampal volumetric integrity as measured by the HPF and the coupling between the HPF and brain atrophy during AD progression. Methods: We included data from 143 cognitively normal (CN), 101 mild cognitive impairment (MCI), and 125 AD participants. We examined group differences in the HPF, …associations between HPF and cognitive ability, and coupling between the HPF and cortical grey matter volume in the CN, MCI, and AD groups. Results: We observed progressive decreases in HPF from CN to MCI and from MCI to AD, and increases in the asymmetry of HPF, with the lowest asymmetry index (AI) in the CN group and the highest AI in the AD group. There was a significant association between HPF and cognitive ability across participants. The coupling between HPF and cortical regions was observed in bilateral hippocampus, parahippocampal gyrus, temporal, frontal, and occipital regions, thalamus, and amygdala in CN, MCI, and AD groups, with a greater involvement of temporal, occipital, frontal, and subcortical regions in MCI and AD patients, especially in AD patients. Conclusion: This study provides novel evidence for the neuroanatomical basis of cognitive decline and brain atrophy during AD progression, which may have important clinical implications for the prognosis of AD. Show more

Keywords: Alzheimer’s disease, brain atrophy, cognitive decline, cortical grey matter volume, hippocampal parenchymal fraction, hippocampus

DOI: 10.3233/JAD-230124

Citation: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 791-801, 2023

Authors: Castellani, Rudolph J. | Shanes, Elisheva D. | McCord, Matthew | Reish, Nicholas J. | Flanagan, Margaret E. | Mesulam, M-Marsel | Jamshidi, Pouya

Article Type: Research Article

Abstract: Host responses to anti-amyloid-β (Aβ) antibody therapy are evident in neuroimaging changes and clinical symptoms in a subset of clinical trial subjects receiving such therapy. The pathological basis for the imaging changes and clinical symptoms is not known, nor is the precise mechanism of Aβ clearing. We report the autopsy findings in a 65-year-old woman who received three open label infusions of the experimental anti-Aβ drug lecanemab over about one month. Four days after the last infusion, she was treated with tissue plasminogen activator for acute stroke symptoms and died several days later with multifocal hemorrhage. Neuropathological examination demonstrated …histiocytic vasculitis involving blood vessels with cerebral amyloid angiopathy. Fragmentation and phagocytosis of vascular Aβ were present throughout the cerebral cortex. Phagocytosis of parenchymal Aβ plaques was noted. Changes suggestive of Aβ and phosphorylated tau “clearing” were also noted. The findings overall suggest that anti-Aβ treatment stimulated a host response to Aβ, i.e., target engagement. The findings also provide evidence that amyloid-related imaging abnormalities might be indicative of an Aβ phagocytic syndrome within cerebral vasculature and parenchymal brain tissue in some cases. Show more

Keywords: Alzheimer’s disease, amyloid-β , amyloid-related imaging abnormalities, Apolipoprotein E, cerebral amyloid angiopathy, hemorrhage, lecanemab, phosphorylated tau, vasculitis

DOI: 10.3233/JAD-221305

Citation: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 803-813, 2023

Authors: Fletcher, Evan

Article Type: Article Commentary

Abstract: Current research trends emphasize complex models of cognitive outcomes, with multiple, interacting predictors, including factors amenable to interventions toward sustaining healthy cognitive aging. Such models often require advanced analysis techniques. The article by Stark et al., ‘Partial least squares regression analysis of Alzheimer’s disease biomarkers, modifiable health variables, and cognitive change in older adults with mild cognitive impairment’, uses partial least squares regression to examine the associations to memory and executive change of 29 biomarker and demographic variables. This commentary discusses the significance of their results and methods within the context of current research foci.

Keywords: Alzheimer’s disease, biomarkers, cognitive change, partial least squares analysis

DOI: 10.3233/JAD-230304

Citation: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 815-819, 2023