Journal of Alzheimer's Disease - Volume 45, issue 3

Authors: Elahi, Sahar | Bachman, Alvin H. | Lee, Sang Han | Sidtis, John J. | Ardekani, Babak A. | for the Alzheimer's Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Corpus callosum (CC) size and shape have been previously studied in Alzheimer’s disease (AD) with the majority of studies having been cross-sectional. Due to the large variance in normal CC morphology, cross-sectional studies are limited in statistical power. Determining individual rates of change requires longitudinal data. Physiological changes are particularly relevant in mild cognitive impairment (MCI), in which CC morphology has not been previously studied longitudinally. Objective: To study temporal rates of change in CC morphology in MCI patients over a one-year period, and to determine whether these rates differ between MCI subjects who converted to AD …(MCI-C) and those who did not (MCI-NC) over an average (±SD) observation period of 5.4 (±1.6) years. Methods: We used a novel multi-atlas based algorithm to segment the mid-sagittal cross-sectional area of the CC in longitudinal MRI scans. Rates of change of CC circularity, total area, and five sub-areas were compared between 57 MCI-NC and 81 MCI-C subjects. Results: The CC became less circular (−0.89% per year in MCI-NC, −1.85% per year in MCI-C) with time, with faster decline in MCI-C (p = 0.0002). In females, atrophy rates were higher in MCI-C relative to MCI-NC in total CC area (p = 0.0006), genu/rostrum (p = 0.005), and splenium (0.002). In males, these rates did not differ between groups. Conclusion: A greater than normal decline in CC circularity was shown to be an indicator of prodromal AD in MCI subjects. This measure is potentially useful as an imaging biomarker of disease and a therapeutic target in clinical trials. Show more

Keywords: Alzheimer's disease, brain, circularity, corpus callosum, magnetic resonance imaging, mild cognitive impairment, shape analysis

DOI: 10.3233/JAD-142631

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 921-931, 2015

Authors: Gray, Nora E. | Sampath, Harini | Zweig, Jonathan A. | Quinn, Joseph F. | Soumyanath, Amala

Article Type: Research Article

Abstract: Background: We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-β (Aβ)-induced cognitive deficits in vivo, and prevents Aβ-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown. Objective: The goal of this study was to identify biochemical pathways altered by CAW using in vitro models of Aβ toxicity. Methods: The effects of CAW on aberrations in antioxidant response, calcium homeostasis, and mitochondrial function induced by Aβ were evaluated in MC65 and SH-SY5Y neuroblastoma cells. Results: CAW decreased intracellular reactive oxygen species and calcium levels elevated …in response to Aβ, and induced the expression of antioxidant response genes in both cell lines. In SH-SY5Y cells, CAW increased basal and maximal oxygen consumption without altering spare capacity, and attenuated Aβ-induced decreases in mitochondrial respiration. CAW also prevented Aβ-induced decreases in ATP and induced the expression of mitochondrial genes and proteins in both cell types. Caffeoylquinic acids from CAW were shown to have a similar effect on antioxidant and mitochondrial gene expression in neuroblastoma cells. Primary rat hippocampal neurons treated with CAW also showed an increase in mitochondrial and antioxidant gene expression. Conclusions: These data suggest an effect of CAW on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes and normalizing calcium homeostasis, likely contributes to its neuroprotective action against Aβ toxicity. Show more

Keywords: Amyloid-β toxicity, calcium homeostasis, Centella asiatica, mitochondrial dysfunction, neuroprotection, reactive oxygen species

DOI: 10.3233/JAD-142217

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 933-946, 2015

Authors: Vasavada, Megha M. | Wang, Jianli | Eslinger, Paul J. | Gill, David J. | Sun, Xiaoyu | Karunanayaka, Prasanna | Yang, Qing X.

Article Type: Research Article

Abstract: Background: Olfactory deficits are prevalent in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). These symptoms precede clinical onset of cognitive and memory deficits and coincide with AD pathology preferentially in the central olfactory structures, suggesting a potential biomarker for AD early detection and progression. Objective: Therefore, we tested the hypothesis that structural degeneration of the primary olfactory cortex (POC) could be detected in AD as well as in MCI patients and would be correlated with olfactory functional magnetic resonance imaging (fMRI) alterations, reflecting loss of olfactory cortex activity. Methods: Total structural volumes and …fMRI activation volumes of the POC and hippocampus were measured along with olfactory and cognitive behavioral tests in 27 cognitively normal (CN), 21 MCI, and 15 AD subjects. Results: Prominent atrophy in the POC and hippocampus was found in both AD and MCI subjects and correlated with behavioral measurements. While behavioral and volumetric measurements showed a gradual decline from CN to MCI to AD, olfactory activation volume in the POC and hippocampus showed a steeper decline in the MCI group compared to corresponding tissue volume, resembling the AD group. Conclusions: Decline in olfactory activity was correlated with the AD structural degeneration in the POC. A more prominent olfactory activity deficit than that of behavioral and tissue volume measurements was shown in the MCI stage. Olfactory fMRI may thus provide an earlier and more sensitive measure of functional neurodegeneration in AD and MCI patients. Show more

Keywords: Alzheimer's disease, functional MRI, mild cognitive impairment, MRI, olfaction

DOI: 10.3233/JAD-141947

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 947-958, 2015

Authors: Berisha, Visar | Wang, Shuai | LaCross, Amy | Liss, Julie

Article Type: Research Article

Abstract: Changes in some lexical features of language have been associated with the onset and progression of Alzheimer's disease. Here we describe a method to extract key features from discourse transcripts, which we evaluated on non-scripted news conferences from President Ronald Reagan, who was diagnosed with Alzheimer's disease in 1994, and President George Herbert Walker Bush, who has no known diagnosis of Alzheimer's disease. Key word counts previously associated with cognitive decline in Alzheimer's disease were extracted and regression analyses were conducted. President Reagan showed a significant reduction in the number of unique words over time and a significant increase in …conversational fillers and non-specific nouns over time. There was no significant trend in these features for President Bush. Show more

Keywords: Early diagnosis, language, medical informatics, natural language processing

DOI: 10.3233/JAD-142763

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 959-963, 2015

Authors: Perrone, Lorena | Grant, William B.

Article Type: Research Article

Abstract: Background: Considerable evidence indicates that diet is an important risk-modifying factor for Alzheimer’s disease (AD). Evidence is also mounting that dietary advanced glycation end products (AGEs) are important risk factors for AD. Objective: This study strives to determine whether estimated dietary AGEs estimated from national diets and epidemiological studies are associated with increased AD incidence. Methods: We estimated values of dietary AGEs using values in a published paper. We estimated intake of dietary AGEs from the Washington Heights-Inwood Community Aging Project (WHICAP) 1992 and 1999 cohort studies, which investigated how the Mediterranean diet (MeDi) affected AD …incidence. Further, AD prevalence data came from three ecological studies and included data from 11 countries for 1977–1993, seven developing countries for 1995–2005, and Japan for 1985–2008. The analysis used dietary AGE values from 20 years before the AD prevalence data. Results: Meat was always the food with the largest amount of AGEs. Other foods with significant AGEs included fish, cheese, vegetables, and vegetable oil. High MeDi adherence results in lower meat and dairy intake, which possess high AGE content. By using two different models to extrapolate dietary AGE intake in the WHICAP 1992 and 1999 cohort studies, we showed that reduced dietary AGE significantly correlates with reduced AD incidence. For the ecological studies, estimates of dietary AGEs in the national diets corresponded well with AD prevalence data even though the cooking methods were not well known. Conclusion: Dietary AGEs appear to be important risk factors for AD. Show more

Keywords: Advanced glycation end products, Alzheimer's disease, cheese, diet, ecological, fish, Japan, meat, mediterranean diet, MeDi

DOI: 10.3233/JAD-140720

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 965-979, 2015

Article Type: Other

DOI: 10.3233/JAD-150003

Citation: Journal of Alzheimer's Disease, vol. 45, no. 3, pp. 981-984, 2015