Journal of Alzheimer's Disease - Volume 65, issue 3

Authors: Gómez, Carlos | Juan-Cruz, Celia | Poza, Jesús | Ruiz-Gómez, Saúl J. | Gomez-Pilar, Javier | Núñez, Pablo | García, María | Fernández, Alberto | Hornero, Roberto

Article Type: Research Article

Abstract: Neuroimaging techniques have demonstrated over the years their ability to characterize the brain abnormalities associated with different neurodegenerative diseases. Among all these techniques, magnetoencephalography (MEG) stands out by its high temporal resolution and noninvasiveness. The aim of the present study is to explore the coupling patterns of resting-state MEG activity in subjects with mild cognitive impairment (MCI). To achieve this goal, five minutes of spontaneous MEG activity were acquired with a 148-channel whole-head magnetometer from 18 MCI patients and 26 healthy controls. Inter-channel relationships were investigated by means of two complementary coupling measures: coherence and Granger causality. Coherence is a …classical method of functional connectivity, while Granger causality quantifies effective (or causal) connectivity. Both measures were calculated in the five conventional frequency bands: delta (δ , 1–4 Hz), theta (θ , 4–8 Hz), alpha (α, 8–13 Hz), beta (β, 13–30 Hz), and gamma (γ , 30–45 Hz). Our results showed that connectivity values were lower for MCI patients than for controls in all frequency bands. However, only Granger causality revealed statistically significant differences between groups (p -values < 0.05, FDR corrected Mann-Whitney U-test), mainly in the beta band. Our results support the role of MCI as a disconnection syndrome, which elicits early alterations in effective connectivity patterns. These findings can be helpful to identify the neural substrates involved in prodromal stages of dementia. Show more

Keywords: Coherence, connectivity, Granger causality, magnetoencephalography (MEG), mild cognitive impairment, neuroimaging

DOI: 10.3233/JAD-170475

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 843-854, 2018

Authors: Zhang, Yudong | Wang, Shuihua | Sui, Yuxiu | Yang, Ming | Liu, Bin | Cheng, Hong | Sun, Junding | Jia, Wenjuan | Phillips, Preetha | Gorriz, Juan Manuel

Article Type: Research Article

Abstract: Background: The number of patients with Alzheimer’s disease is increasing rapidly every year. Scholars often use computer vision and machine learning methods to develop an automatic diagnosis system. Objective: In this study, we developed a novel machine learning system that can make diagnoses automatically from brain magnetic resonance images. Methods: First, the brain imaging was processed, including skull stripping and spatial normalization. Second, one axial slice was selected from the volumetric image, and stationary wavelet entropy (SWE) was done to extract the texture features. Third, a single-hidden-layer neural network was used as the classifier. Finally, a …predator-prey particle swarm optimization was proposed to train the weights and biases of the classifier. Results: Our method used 4-level decomposition and yielded 13 SWE features. The classification yielded an overall accuracy of 92.73±1.03%, a sensitivity of 92.69±1.29%, and a specificity of 92.78±1.51%. The area under the curve is 0.95±0.02. Additionally, this method only cost 0.88 s to identify a subject in online stage, after its volumetric image is preprocessed. Conclusion: In terms of classification performance, our method performs better than 10 state-of-the-art approaches and the performance of human observers. Therefore, this proposed method is effective in the detection of Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, detection, particle swarm optimization, predator-prey model, single-hidden-layer neural network, stationary wavelet entropy

DOI: 10.3233/JAD-170069

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 855-869, 2018

Authors: Tan, Meng-Shan | Wang, Ping | Ma, Fang-Chen | Li, Jie-Qiong | Tan, Chen-Chen | Yu, Jin-Tai | Tan, Lan | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: Recent studies found the variants in Alzheimer’s disease (AD) risk gene PLD3 were associated with cognitive function, but its detailed mechanism before typical AD onset was unknown. Our current study examined the impact of PLD3 common variant rs11667768 on cerebrospinal fluid (CSF) total-tau and phosphorylated-tau levels and structural MRI from the ADNI database. We found rs11667768 was significantly associated with CSF total-tau levels and hippocampal volumes at baseline and six-year follow-up in the total non-demented elderly group and the mild cognitive impairment subgroup, indicating a potential role of PLD3 common variants in influencing cognitive function through changing …CSF total-tau levels and hippocampal volumes. Show more

Keywords: Alzheimer’s Disease neuroimaging initiative, common variant, hippocampus, mild cognitive impairment, PLD3 ,  tau

DOI: 10.3233/JAD-180431

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 871-876, 2018

Authors: Keret, Ophir | Shochat, Tzippy | Steiner, Israel | Glik, Amir

Article Type: Research Article

Abstract: Early-onset Alzheimer’s disease (EOAD) accounts for 1–5% of Alzheimer’s disease cases and is associated with specific ethnicities. It has been our impression that non-Ashkenazi Jews have a higher rate of EOAD and we therefore explored this hypothesis. We performed a retrospective case control study of EOAD cases referred to our cognitive neurology clinic between January 1999 and December 2016. Patients (n  = 129) were compared to age- and geographically-matched controls generated from the Second Israeli National Health Survey (n  = 1,811). Data on country of origin, education, dementia family history, depression, and vascular risk factors were compared between the groups. The association …of non-Ashkenazi Jewish heritage and country of origin with EOAD was calculated using a logistic multivariate regression model. The EOAD group’s mean age was 59.6±4.1 years, with a female predominance (64.3%). The EOAD group had a higher percentage of individuals of non-Ashkenazi Jewish origin (64.3% versus 51.4%, p  = 0.003) and of Yemenite descent in particular (16.28% versus 6.24%, p  < 0.001). On multiple logistic regression analysis, Yemenite Jewish origin was an independently associated with EOAD (OR 2.54, 95% CI 1.4–4.8). There were no significant differences in parameters between non-Ashkenazi and Ashkenazi Jews. Only 4.6% of EOAD cases had a positive EOAD family history. In conclusion, EOAD is over-represented among non-Ashkenazi Jews. Yemenite origin is independently associated with EOAD and the majority of patients with EOAD have no family history of Alzheimer’s disease. Further evaluation with genetic studies is warranted. Show more

Keywords: Alzheimer’s disease, early-onset dementia, early onset Alzheimer’s disease, ethnicity, young onset dementia

DOI: 10.3233/JAD-180331

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 877-884, 2018

Authors: Ritchie, Karen | Carrière, Isabelle | Howett, David | Su, Li | Hornberger, Michael | O’Brien, John T. | Ritchie, Craig W. | Chan, Dennis

Article Type: Research Article

Abstract: Impairments in spatial processing due to hippocampal degeneration have been observed in the years immediately preceding the diagnosis of Alzheimer’s disease (AD) dementia. The demonstration of changes in spatial processing in preceding decades would provide a cognitive marker for pre-clinical AD and an outcome measure for early intervention trials. The present study examined allocentric and egocentric spatial processing in relation to future dementia risk in a middle-aged cohort. The CAIDE Dementia Risk Score (DRS) was calculated for 188 persons aged 40 to 59, of whom 94 had a parent with dementia. Participants underwent the Four Mountains Test (4MT) of allocentric …spatial processing, the Virtual Reality Supermarket Trolley Task (VRSTT) of egocentric spatial processing, and 3T MRI scans. A significant negative association was found between the DRS and 4MT (Spearman correlation – 0.26, p  = 0.0006), but not with the VRSTT. The 4MT was also found to be a better predictor of risk than tests of episodic memory, verbal fluency, or executive functioning. The results suggest that allocentric rather than egocentric processing may be a potential indicator of risk for late-onset AD, consistent with the hypothesis that the earliest cognitive changes in AD are driven by tau-related degeneration in the medial temporal lobe rather than amyloid-only deposition in the medial parietal lobe. Show more

Keywords: Alzheimer’s disease, cognition, diagnosis, magnetic resonance imaging, neuropsychology, preclinical, prognosis, spatial memory

DOI: 10.3233/JAD-180432

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 885-896, 2018

Authors: Lizio, Roberta | Babiloni, Claudio | Del Percio, Claudio | Losurdo, Antonia | Vernò, Lucia | De Tommaso, Marina | Montemurno, Anna | Dalfino, Giuseppe | Cirillo, Pietro | Soricelli, Andrea | Ferri, Raffaele | Noce, Giuseppe | Pascarelli, Maria Teresa | Catania, Valentina | Nobili, Flavio | Famá, Francesco | Orzi, Francesco | Giubilei, Franco | Buttinelli, Carla | Triggiani, A. Ivano | Frisoni, Giovanni B. | Scisci, Anna Maria | Mastrofilippo, Nicola | Procaccini, Deni Aldo | Gesualdo, Loreto

Article Type: Research Article

Abstract: This study tested whether resting state alpha rhythms (8–13 Hz) may characterize mild cognitive impairment due to Alzheimer’s disease (ADMCI) compared with MCI due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45 cognitively normal elderly (Nold) subjects were available in a national archive. Age, gender, and education were matched in the three groups, and Mini-Mental State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta (<4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz), and gamma (30–40 Hz) cortical sources were …estimated by eLORETA freeware and classified across individuals by area under the receiver operating characteristic curve (AUROCC). Compared with Nold group, posterior alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In contrast, widespread delta source activities were greater in CKDMCI than ADMCI group. These source activities correlated with the MMSE score and correctly classified between Nold and all MCI individuals (AUROCC = 0.8–0.85) and between ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD affects cortical neural synchronization at alpha frequencies underpinning brain arousal and low vigilance in the quiet wakefulness. In contrast, CKD may principally affect cortical neural synchronization at the delta frequencies. Future prospective cross-validation studies will have to test these candidate rsEEG markers for clinical applications and drug discovery. Show more

Keywords: Exact low resolution brain electromagnetic source tomography (eLORETA), mild cognitive impairment due to Alzheimer’s disease (ADMCI), mild cognitive impairment due to chronic kidney disease (CKDMCI), receiver operating characteristic (ROC) curve, resting state electroencephalographic (rsEEG) rhythms

DOI: 10.3233/JAD-180245

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 897-915, 2018

Authors: van Duinkerken, Eelco | Farme, Juliana | Landeira-Fernandez, Jesus | Dourado, Marcia C. | Laks, Jerson | Mograbi, Daniel C.

Article Type: Research Article

Abstract: The capacity to make decisions is an important feature of daily living, which is closely linked to proper cognitive functioning. In conditions in which cognitive functioning becomes compromised, such as in Alzheimer’s disease (AD), decision-making capacity can also get affected. Especially in AD, this has important implications, since over the course of the condition many important clinical decisions have to be made. For caregivers as well as physicians, it is sometimes difficult to determine how and when to intervene in the decision-making process. The aim of this systematic literature review was to identify studies that have evaluated medical and research …consent decision-making capacity in patients with AD. Studies consistently show that decision-making capabilities are impaired in patients with AD. The cognitive and neuronal correlates of this process are, however, poorly studied. The few studies that investigated correlations have shown worse cognitive performance, mainly on the MMSE, to be related to poorer decision-making capacity. As most of these correlations have been performed in groups combining patients and controls, it remains unknown if these associations are disease specific. There is a need to study more systematically the decision-making process in relation to cognitive functioning and neural correlates to be able to develop a framework of decision-making capacity in AD, ultimately aiding clinicians and caregivers to understand and evaluate those capabilities in patients. Show more

Keywords: Alzheimer’s disease, cognition, decision-making, neuroimaging, systematic review

DOI: 10.3233/JAD-180311

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 917-930, 2018

Authors: Simon, Sharon S. | Tusch, Erich S. | Feng, Nicole C. | Håkansson, Krister | Mohammed, Abdul H. | Daffner, Kirk R.

Article Type: Research Article

Abstract: Background: Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. Objective: To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. Methods: Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned …to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants’ homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used as outcome measures. Results: The groups were comparable at baseline. The Adaptive group showed robust gains in the trained tasks, and there was a time-by-group interaction for the Digit Symbol test, with significant improvement only after Adaptive training. In addition, the magnitude of the intervention effect was similar at both sites. Conclusion: Home-based CCT Adaptive WM training appears more effective than Non-Adaptive training in older adults from different cultural backgrounds. We present evidence of improvement in trained tasks and on a demanding untrained task dependent upon WM and processing speed. The benefits over the active control group suggest that the Adaptive CCT gains were linked to providing a continuously challenging level of WM difficulty. Show more

Keywords: Aging, computerized cognitive training, randomized controlled trial, working memory

DOI: 10.3233/JAD-180455

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 931-949, 2018

Authors: Gao, Ling | Jiang, Yu | Wei, Shan | Shang, Suhang | Li, Pei | Chen, Chen | Dang, Liangjun | Wang, Jin | Huo, Kang | Deng, Meiying | Wang, Jingyi | Zhang, Rong | Qu, Qiumin

Article Type: Research Article

Abstract: Background: Transport proteins, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), and soluble receptor of advanced glycation end products (sRAGE), play an important role in the clearance of plasma amyloid-β (Aβ). However, their relationship is not clear. Objective: The aim was to explore the relationship between plasma levels of sLRP1, sRAGE, and Aβ in a cross-sectional study. Methods: A total of 1,185 cognitively normal participants (age above 40) from a village in the suburbs of Xi’an, China were enrolled from October 8, 2014 to March 30, 2015. Plasma Aβ40 , Aβ42 , sLRP1, and sRAGE were tested using …a commercial ELISA. Apolipoprotein E (APOE ) genotyping was conducted using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE, and Aβ was analyzed using Pearson’s correlation analysis and multiple linear regression. Results: In the total population, Log sLRP1 and Log sRAGE were positively correlated with plasma Aβ40 (r = 0.103, p  < 0.001; r = 0.064, p  = 0.027, respectively), but neither were associated with plasma Aβ42 . After multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were still positively related with plasma Aβ40 (β= 2.969, p  < 0.001; β= 1.936, p  = 0.017, respectively) but not Aβ42 . Furthermore, the positive correlations between transport proteins and plasma Aβ40 remained significant only in APOE ɛ 4 non-carriers after Pearson’s analysis and multiple regression analysis after stratification by gene status. Conclusion: The concentrations of plasma sLRP1 and sRAGE had a significant impact on the level of plasma Aβ40 in cognitively normal adults, especially in APOE ɛ 4 non-carriers. However, the mechanism by which the transport proteins are involved in peripheral Aβ clearance and the relationship between transporters and amyloid burden in the brain needs further validation. Show more

Keywords: Alzheimer’s disease, amyloid-β, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor of advanced glycation end products (sRAGE), transport proteins

DOI: 10.3233/JAD-180399

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 951-961, 2018

Authors: Zaletel, Ivan | Schwirtlich, Marija | Perović, Milka | Jovanović, Mirna | Stevanović, Milena | Kanazir, Selma | Puškaš, Nela

Article Type: Research Article

Abstract: Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer’s disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a …severe and very early development of amyloid pathology. Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine. Show more

Keywords: Amyloid plaque, dementia, familial Alzheimer’s disease, neural differentiation, neurogenesis, SOXB1, SOXB2 5xFAD, transcription factor

DOI: 10.3233/JAD-180277

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 963-976, 2018