Journal of Alzheimer's Disease - Volume 45, issue 4

Authors: Richard, Bernhard Clemens | Kurdakova, Anastasiia | Baches, Sandra | Bayer, Thomas A. | Weggen, Sascha | Wirths, Oliver

Article Type: Research Article

Abstract: In the present report, we extend previous findings in the 5XFAD mouse model with regard to a characterization of behavioral deficits and neuropathological alterations. We demonstrate that these mice develop a robust age-dependent motor phenotype and spatial reference memory deficits when bred to homozygosity, leading to a strongly reduced age of onset of behavioral symptoms. At postnatal day sixteen, abundant AβPP was detected in subiculum and cortical pyramidal neurons. From six weeks on, intraneuronal Aβ could be detected which was much more abundant in homozygous mice. The same gene-dosage effect was seen on memory and motor deficits. While at 2 …months of age neither heterozygous nor homozygous 5XFAD mice show any neurological phenotype except for alterations in anxiety behavior, at 5 months they were clearly evident. Interestingly, despite abundant motor deficiencies, homozygous 5XFAD mice were able to perform the acquisition training of the Morris water maze task with no difference in the swimming performance between the groups. Therefore the aggravated spatial memory and spatial reference memory deficits of the homozygous mice correlated with the elevated soluble and insoluble Aβ levels. Homozygous 5XFAD mice represent a model with several advantages in comparison to the heterozygous mice, developing amyloid pathology much more rapidly together with a neurological phenotype. These advantages allow reducing the number of animals for Alzheimer's disease research. Show more

Keywords: Amyloid, axonal degeneration, behavior, intraneuronal Aβ, motor deficit, spatial memory, transgenic mice, 5XFAD

DOI: 10.3233/JAD-143120

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1223-1236, 2015

Authors: Vassilaki, Maria | Cha, Ruth H. | Aakre, Jeremiah A. | Therneau, Terry M. | Geda, Yonas E. | Mielke, Michelle M. | Knopman, David S. | Petersen, Ronald C. | Roberts, Rosebud O.

Article Type: Research Article

Abstract: Background: Etiologic differences in mild cognitive impairment (MCI) subtypes may impact mortality. Objective: To assess the rate of death in MCI overall, and by subtype, in the population-based Mayo Clinic Study of Aging. Methods: Participants aged 70–89 years at enrollment were clinically evaluated at baseline and 15-month intervals to assess diagnoses of MCI and dementia. Mortality in MCI cases versus cognitively normal (CN) individuals was estimated using Cox proportional hazards models. Results: Over a median follow-up of 5.8 years, 331 of 862 (38.4%) MCI cases and 224 of 1,292 (17.3%) cognitively normal participants died. …Compared to CN individuals, mortality was elevated in persons with MCI (hazard ratio [HR] = 2.03; 95% CI: 1.61 to 2.55), and was higher for non-amnestic MCI (naMCI; HR = 2.47; 95% CI: 1.80 to 3.39) than for amnestic MCI (aMCI; HR = 1.89; 95% CI: 1.48 to 2.41) after adjusting for confounders. Mortality varied significantly by sex, education, history of heart disease, and engaging in moderate physical exercise (p for interaction <0.05 for all). Mortality rate estimates were highest in MCI cases who were men, did not exercise, had heart disease, and had higher education versus CN without these factors, and for naMCI cases versus aMCI cases without these factors. Conclusions: These findings suggest stronger impact of etiologic factors on naMCI mortality. Prevention of heart disease, exercise vigilance, may reduce MCI mortality and delayed MCI diagnosis in persons with higher education impacts mortality. Show more

Keywords: Cohort studies, incidence studies, mild cognitive impairment, mortality, outcomes research, prognosis

DOI: 10.3233/JAD-143078

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1237-1245, 2015

Authors: Wisse, Laura E.M. | Reijmer, Yael D. | ter Telgte, Annemieke | Kuijf, Hugo J. | Leemans, Alexander | Luijten, Peter R. | Koek, Huiberdina L. | Geerlings, Mirjam I. | Biessels, Geert Jan | on behalf of the Utrecht Vascular Cognitive Impairment (VCI) Study Group

Article Type: Research Article

Abstract: Background: In patients with Alzheimer’s disease (AD), atrophy of the entorhinal cortex (ERC) and hippocampal formation may induce degeneration of connecting white matter tracts. Objective: We examined the association of hippocampal subfield and ERC atrophy at 7 tesla MRI with fornix and parahippocampal cingulum (PHC) microstructure in patients with early AD. Methods: Twenty-five patients with amnestic mild cognitive impairment (aMCI) (n = 15) or early AD (n = 10) and 17 controls underwent 3 tesla diffusion MRI to obtain fractional anisotropy (FA) of the fornix and PHC and 7 tesla MRI to obtain ERC and hippocampal …subfield volumes. Linear regression analyses were performed, adjusted for age, gender, and intracranial volume. Results: Fornix FA was significantly lower and subiculum, cornu ammonis (CA) 1, and dentate gyrus &CA4 volume were significantly smaller in patients with MCI or AD as compared to controls. In patients with MCI or AD, fornix FA was positively associated with subiculum volume (β = 0.53, 95% CI 0.10; 0.96), but not with ERC/other subfield volumes. PHC FA was not associated with ERC/subfield volumes. Conclusion: These findings indicate that in early AD subiculum atrophy is associated with lower FA of the fornix, which primarily consists of axons originating in the subiculum. This suggests that degeneration of subicular cell bodies and their axons are related processes in early AD. Show more

Keywords: Alzheimer's disease, diffusion magnetic resonance imaging, fornix, hippocampus, mild cognitive impairment, subiculum

DOI: 10.3233/JAD-142994

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1247-1256, 2015

Authors: Kowoll, Magdalena Eva | Degen, Christina | Gladis, Saskia | Schröder, Johannes

Article Type: Research Article

Abstract: Bilingualism is associated with enhanced executive functioning and delayed onset of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here, we investigated neuropsychological differences between mono- and bilingual patients with MCI and AD as well as the respective effects of dementia on the dominant and non-dominant language of bilinguals. 69 patients with MCI (n = 22) or AD (n = 47) and 17 healthy controls were included. 41 subjects were classified as lifelong bilinguals (mean age: 73.6; SD = 11.5) and 45 as monolinguals (mean age: 78.1; SD = 10.9). Neuropsychological performance was assessed on the CERAD-NP, the clock-drawing …test, and the logical memory subscale of the Wechsler Memory Scale. Neuropsychological profiles showed only minor nonsignificant differences between mono- and bilingual subjects when compared between diagnostic groups. Bilingual MCI patients scored significantly lower on the verbal fluency and picture naming task in their dominant language than bilingual controls. Bilingual AD patients showed a reduced performance in their nondominant language when compared to bilingual MCI patients and bilingual controls (main effect language dominance: verbal fluency task p < 0.001; BNT p < 0.001). Bilingual MCI and AD patients show a similar pattern of neuropsychological deficits as monolingual patients do. The dominant language appears to be compromised first in bilingual MCI patients, while severe deficits of the nondominant language develop later in the course with manifestation of AD. These findings are important for the diagnostic work up of bilingual patients and the development of improved care concepts for bilingual patients such as migrant populations. Show more

Keywords: Alzheimer's disease, bilingualism, mild cognitive impairment, picture naming, verbal fluency

DOI: 10.3233/JAD-142880

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1257-1268, 2015

Article Type: Correction

DOI: 10.3233/JAD-159002

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1269-1270, 2015

Article Type: Other

DOI: 10.3233/JAD-150005

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1271-1273, 2015

Article Type: Other

DOI: 10.3233/JAD-2015-45427

Citation: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1275-1287, 2015