Journal of Alzheimer's Disease - Volume 82, issue 2

Authors: Schoemaker, Dorothee | Velilla-Jimenez, Lina | Zuluaga, Yesica | Baena, Ana | Ospina, Carolina | Bocanegra, Yamile | Alvarez, Sergio | Ochoa-Escudero, Martin | Guzmán-Vélez, Edmarie | Martinez, Jairo | Lopera, Francisco | Arboleda-Velasquez, Joseph F. | Quiroz, Yakeel T.

Article Type: Research Article

Abstract: Background: Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer’s disease and vascular dementia. Objective: Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer’s disease and vascular dementia. Methods: We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer’s disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts …and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score. Results: In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = –0.06, p  < 0.05) and an increased severity of cerebral microbleeds (B = 0.13, p  < 0.001), lacunes (B = 0.30, p  < 0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p  < 0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p  < 0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD. Conclusion: Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks. Show more

Keywords: Autosomal dominant Alzheimer’s disease, CADASIL, cardiovascular risk factors, cerebral small vessel disease, cognition, magnetic resonance imaging

DOI: 10.3233/JAD-210313

Citation: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 841-853, 2021

Authors: Niu, Jiahui | Iqbal, Khalid | Liu, Fei | Hu, Wen

Article Type: Research Article

Abstract: Background: Women have a two-fold higher risk than men to Alzheimer’s disease (AD) at midlife. Larger brain tau burden was consistently shown in older women than age-matched men. The biological basis for this gender disparity remains elusive. Objective: We sought to know whether tau expression and phosphorylation physiologically differ between males and females. Methods: We used western blots and immunohistochemistry to compare the levels of total tau and phosphorylated tau in the hippocampus and entorhinal cortex (EC) between sexes in Wistar rats at 40 days, and 8 and 20 months of age. Results: We …detected no statistically significant difference in total tau, 3R-tau, and 4R-tau between sexes. However, female rats exhibited lower levels of tau unphosphorylated at the Tau-1 site at 40 days of age. At 8 months of age, females showed higher levels of tau phosphorylated at Ser190 , Ser387 , and Ser395 (Ser199 , Ser396 , and Ser404 of human tau, respectively) than males in EC. At 20 months of age, both brain regions of female rats consistently showed higher levels than males of tau phosphorylated at Ser253 , Ser387 , PHF-1 (Ser387/395 ), and Ser413 sites, which correspond to Ser262 , Ser396 , Ser396/404 , and Ser422 of human tau, respectively. Conclusion: Rats of both sexes have comparable levels of total tau, 3R-tau, and 4R-tau, whereas females exhibit higher levels of tau phosphorylated at multiple sites that are implicated in AD tau pathology, indicating a sexual dimorphism of tau phosphorylation that may potentially underlie the disparity in brain tau burden and risk for AD between sexes. Show more

Keywords: Alzheimer’s disease, entorhinal cortex, gender, hippocampus, protein phosphorylation, tau expression, tau isoforms

DOI: 10.3233/JAD-210341

Citation: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 855-869, 2021

Authors: Vecchio, Fabrizio | Miraglia, Francesca | Alú, Francesca | Orticoni, Alessandro | Judica, Elda | Cotelli, Maria | Rossini, Paolo Maria

Article Type: Research Article

Abstract: Background: Most common progressive brain diseases in the elderly are Alzheimer’s disease (AD) and vascular dementia (VaD). They present with relatively similar clinical symptoms of cognitive decline, but the underlying pathophysiological mechanisms are different. Objective: The aim is to explore the brain connectivity differences between AD and VaD patients compared to mild cognitive impairment (MCI) and normal elderly (Nold) subjects applying graph theory, in particular the Small World (SW) analysis. Methods: 274 resting state EEGs were analyzed in 100 AD, 80 MCI, 40 VaD, and 54 Nold subjects. Graph theory analyses were applied to undirected and …weighted networks obtained by lagged linear coherence evaluated by eLORETA tool. Results: VaD and AD patients presented more ordered low frequency structure (lower value of SW) than Nold and MCI subjects, and more random organization (higher value of SW) in low and high frequency alpha rhythms. Differences between patients have been found in high frequency alpha rhythms in VaD (higher value of SW) with respect to AD, and in theta band with a trend which is more similar to MCI and Nold than to AD. MCI subjects presented a network organization which is intermediate, in low frequency bands, between Nold and patients. Conclusion: Graph theory applied to EEG data has proved very useful in identifying differences in brain network patterns in subjects with dementia, proving to be a valid tool for differential diagnosis. Future studies will aim to validate this method to diagnose especially in the early stages of the disease and at single subject level. Show more

Keywords: Brain networks, EEG, functional coupling, LORETA, Small World

DOI: 10.3233/JAD-210394

Citation: Journal of Alzheimer's Disease, vol. 82, no. 2, pp. 871-879, 2021