Journal of Alzheimer's Disease - Volume 68, issue 2

Authors: Hackney, Madeleine E. | McCullough, Lauren E. | Bay, Allison A. | Silverstein, Hayley A. | Hart, Ariel R. | Shin, Ryan J. | Wharton, Whitney

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a devastating progressive neurodegenerative disease resulting in memory loss and a severe reduction in ability to perform activities of daily living. The role of caring for someone with AD frequently falls to female family members, often daughters. The burden of caregiving can increase stress and anxiety and cause health decline in the caregiver. The combination of ethnicity-related genetic factors promoting the development of dementias among African-Americans (AA) and the increased risk among women for developing AD means that AA women who are caregivers of a parent with AD are at great risk for developing dementias including …AD. The proposed study would compare the cognitive, motor, and psychosocial benefits of a well-established 12 week, 20-lesson adapted Argentine Tango intervention (N = 30) to a no-contact control group (N = 10) in middle-aged (45–65 years) AA women who are caregivers of a parent with AD in the metro Atlanta area. Show more

Keywords: African American, Alzheimer’s disease, caregiver, clinical trial, dance, inflammation

DOI: 10.3233/JAD-181130

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 767-775, 2019

Authors: Sato, Kenichiro | Mano, Tatsuo | Ihara, Ryoko | Suzuki, Kazushi | Tomita, Naoki | Arai, Hiroyuki | Ishii, Kenji | Senda, Michio | Ito, Kengo | Ikeuchi, Takeshi | Kuwano, Ryozo | Matsuda, Hiroshi | Iwatsubo, Takeshi | Toda, Tatsushi | Iwata, Atsushi | Alzheimer’s Disease Neuroimaging Initiative, and Japanese Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Effect of serum calcium level to the incidence of mild cognitive impairment (MCI) conversion to early Alzheimer’s disease (AD) remains uncertain. Objective: To investigate association between baseline serum calcium and the MCI conversion in the Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI) study cohort. Methods: In this sub-analysis of J-ADNI study, we reviewed data from MCI participants at baseline regarding their conversion to early AD during the 3 years of observation period and assessed the associated factors including serum calcium level. In addition, we compared our results from the J-ADNI study with the corresponding results from …the North American (NA)-ADNI. Results: Of 234 eligible MCI participants from the J-ADNI cohort, 121 (51.7%) converted to AD during the first 36 months of observation. Using univariate analysis, being female, having shorter years of education, and lower serum calcium level were correlated with increased risk of MCI-to-AD conversion exclusively in J-ADNI cohort. The lower corrected serum calcium level remained as one of conversion-associated factors in the J-ADNI cohort even after adjustment for multiple confounding variables, although this was not observed in the NA-ADNI cohort. Conclusion: Our findings suggest that lower serum calcium may be associated with an increased risk of MCI conversion to AD in Japanese cohorts. The reason for this correlation remains unclear and further external validation using other Asian cohorts is needed. It would be interesting for future AD studies to obtain serum calcium levels and other related factors, such as vitamin D levels, culture-specific dietary or medication information. Show more

Keywords: Alzheimer’s disease, calcium, conversion, Japanese Alzheimer’s Disease Neuroimaging Initiative, mild cognitive impairment

DOI: 10.3233/JAD-181115

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 777-788, 2019

Authors: Damulina, Anna | Pirpamer, Lukas | Seiler, Stephan | Benke, Thomas | Dal-Bianco, Peter | Ransmayr, Gerhard | Struhal, Walter | Hofer, Edith | Langkammer, Christian | Duering, Marco | Fazekas, Franz | Schmidt, Reinhold

Article Type: Research Article

Abstract: Background/Objective: Higher white matter hyperintensity (WMH) load has been reported in Alzheimer’s disease (AD) patients in different brain regions when compared to controls. We aimed to assess possible differences of WMH spatial distribution between AD patients and age-matched controls by means of lesion probability maps. Methods: The present study included MRI scans of 130 probable AD patients with a mean age of 73.4±8.2 years from the Prospective Dementia Registry Austria Study and 130 age-matched healthy controls (HC) from the Austrian Stroke Prevention Family Study. Risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, coronary artery disease, and smoking were …assessed. Manually segmented FLAIR WMH masks were non-linearly registered to a template and voxel-based probability mapping was performed. Results: There were no significant between-group differences in cardiovascular risk factors and WMH volume. AD patients showed a significantly higher likelihood of having WMH in a bilateral periventricular distribution than controls before and after correcting for age, sex, cardiovascular risk factors, and ventricular volume (p ≤0.05; threshold-free cluster enhancement corrected). There was no significant association between the periventricular WMH volume and cognitive decline of AD patients. Conclusion: In AD, WMH were preferentially found in a periventricular location but the volume of lesions was unrelated to cognitive decline in our study irrespective of lesion location. Show more

Keywords: Alzheimer’s disease, magnetic resonance imaging, periventricular white matter, white matter hyperintensities

DOI: 10.3233/JAD-180982

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 789-796, 2019

Authors: Kasahara, Hiroo | Ikeda, Masaki | Nagashima, Kazuaki | Fujita, Yukio | Makioka, Kouki | Tsukagoshi, Setsuki | Yamazaki, Tsuneo | Takai, Eriko | Sanada, Etsuko | Kobayashi, Ayumi | Kishi, Kazuhiro | Suto, Takayuki | Higuchi, Tetsuya | Tsushima, Yoshito | Ikeda, Yoshio

Article Type: Research Article

Abstract: Neuroimages of cerebral amyloid-β (Aβ) accumulation and small vessel disease (SVD) were examined in patients with various types of cognitive disorders using 11 C-labeled Pittsburgh Compound B-positron emission tomography (PiB-PET) and magnetic resonance imaging (MRI). The mean cortical standardized uptake value ratio (mcSUVR) was applied for a quantitative analysis of PiB-PET data. The severity of white matter lesions (WML) and enlarged perivascular spaces (EPVS) on MRI were assessed to evaluate complicating cerebral SVD using semiquantitative scales. In homozygous apolipoprotein E ɛ 3/ɛ 3 carriers, the incidence of more severe WML and EPVS was higher in PiB-positive than PiB-negative patients, indicating …that WML and EPVS might be associated with enhanced Aβ accumulation. An association study between PiB-PET and MRI findings revealed that higher WML grades significantly correlate with lower mcSUVRs, especially in the frontal area, indicating that more severe ischemic MRI findings are associated with milder Aβ accumulation among patients with Alzheimer’s disease. In these patients SVD may accelerate the occurrence of cognitive decline and facilitate early recognition of dementia. Show more

Keywords: Alzheimer’s disease, amyloid-β, dementia, Pittsburgh Compound B, positron emission tomography, white matter lesion

DOI: 10.3233/JAD-180939

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 797-808, 2019

Authors: Griffith, Chelsea M. | Macklin, Lauren N. | Cai, Yan | Sharp, Andrew A. | Yan, Xiao-Xin | Reagan, Lawrence P. | Strader, April D. | Rose, Gregory M. | Patrylo, Peter R.

Article Type: Research Article

Abstract: Several studies have demonstrated that mouse models of Alzheimer’s disease (AD) can exhibit impaired peripheral glucose tolerance. Further, in the APP/PS1 mouse model, this is observed prior to the appearance of AD-related neuropathology (e.g., amyloid-β plaques; Aβ) or cognitive impairment. In the current study, we examined whether impaired glucose tolerance also preceded AD-like changes in the triple transgenic model of AD (3xTg-AD). Glucose tolerance testing (GTT), insulin ELISAs, and insulin tolerance testing (ITT) were performed at ages prior to (1–3 months and 6–8 months old) and post-pathology (16–18 months old). Additionally, we examined for altered insulin signaling in the hippocampus. …Western blots were used to evaluate the two-primary insulin signaling pathways: PI3K/AKT and MAPK/ERK. Since the PI3K/AKT pathway affects several downstream targets associated with metabolism (e.g., GSK3, glucose transporters), western blots were used to examine possible alterations in the expression, translocation, or activation of these targets. We found that 3xTg-AD mice display impaired glucose tolerance as early as 1 month of age, concomitant with a decrease in plasma insulin levels well prior to the detection of plaques (∼14 months old), aggregates of hyperphosphorylated tau (∼18 months old), and cognitive decline (≥18 months old). These alterations in peripheral metabolism were seen at all time points examined. In comparison, PI3K/AKT, but not MAPK/ERK, signaling was altered in the hippocampus only in 18-20-month-old 3xTg-AD mice, a time point at which there was a reduction in GLUT3 translocation to the plasma membrane. Taken together, our results provide further evidence that disruptions in energy metabolism may represent a foundational step in the development of AD. Show more

Keywords: 3xTg-AD, AKT, Alzheimer’s disease, diabetes, glucose, GLUT, hippocampus, insulin, metabolism

DOI: 10.3233/JAD-180707

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 809-837, 2019

Article Type: Correction

DOI: 10.3233/JAD-189016

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 839-839, 2019

Article Type: Correction

DOI: 10.3233/JAD-189017

Citation: Journal of Alzheimer's Disease, vol. 68, no. 2, pp. 841-841, 2019