Journal of Alzheimer's Disease - Volume 72, issue 3

Authors: Poptsi, Eleni | Tsardoulias, Emmanouil | Moraitou, Despina | Symeonidis, Andreas L. | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are acknowledged stages of the clinical spectrum of Alzheimer’s disease (AD), and cognitive control seems to be among the first neuropsychological predictors of cognitive decline. Existing tests are usually affected by educational level, linguistic abilities, cultural differences, and social status, constituting them error-prone when differentiating between the aforementioned stages. Creating robust neuropsychological tests is therefore prominent. Objective: The design of a novel psychometric battery for the cognitive control and attention assessment, free of demographic effects, capable to discriminate cognitively healthy aging, SCD, MCI, and mild Dementia (mD). …Methods: The battery initial hypothesis was tuned using iterations of administration on random sampling healthy older adults and people with SCD, MCI, and mD, from the area of Thessaloniki, Greece. This resulted in the first release of the REflexes MEasurement DEviceS for Alzheimer battery (REMEDES for Alzheimer-R4Alz). Results: The first release lasts for almost an hour. The battery was design to assess working memory (WM) including WM storage, processing, and updating, enriched by episodic buffer recruitment. It was also designed to assess attention control abilities comprising selective, sustained, and divided attention subtasks. Finally, it comprises an inhibitory control, a task/rule switching or set-shifting, and a cognitive flexibility subtask as a combination of inhibition and task/rule switching abilities. Conclusion: The R4Alz battery is an easy to use psychometric battery with increasing difficulty levels and assumingly ecological validity, being entertaining for older adults, potentially free of demographic effects, and promising as a more accurate and early diagnosis tool of neurodegeneration. Show more

Keywords: Attentional control, cognitive control, dementia, healthy aging, mild cognitive impairment, psychometric assessment, subjective cognitive decline

DOI: 10.3233/JAD-190798

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 783-801, 2019

Authors: Kim, Hong-Bae | Park, Byoungjin | Shim, Jae-Yong

Article Type: Research Article

Abstract: Background: Prevalence of both anemia and cognitive impairment tends to increase with age. Individual studies have recently shown that anemia could be associated with cognitive impairment. Objective: To investigate the association between anemia and cognitive impairment including dementia. Methods: Two of the authors systematically searched PubMed, EMBASE, and the Cochrane library to retrieve observational studies reporting a relationship between anemia and cognitive impairment from 1964 to July 10, 2019. Case-control and cohort studies were included, and odds ratios (ORs) or relative risks (RRs) with 95% confidence intervals (CIs) for the risk of cognitive impairment were calculated …using a random-effects model. Results: In total, 16 observational studies including eight case-control studies and eight cohort studies were included in the final analysis. Anemia was significantly linked to cognitive impairment (OR or RR 1.51; 95% CI: 1.32–1.73) in a random-effects meta-analysis, albeit with medium heterogeneity (I2  = 47.8%). Meta-estimates of dementia from prospective population-based cohort studies were similar (RR 1.46; 95% CI: 1.22–1.76) without substantial heterogeneity (I2  = 23.2%). Conclusion: Our meta-analysis indicates that anemia is associated with cognitive impairment. Further prospective research is warranted to determine the cause-effect relationship of anemia with cognitive impairment and whether treatment of anemia might reduce the risk of dementia. Show more

Keywords: Anemia, cognitive impairment, dementia, meta-analysis, observational study, systematic review

DOI: 10.3233/JAD-190521

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 803-814, 2019

Authors: Chen, Bing | Zheng, Weiming

Article Type: Research Article

Abstract: Upregulation of Rho-associated protein kinase 2 (ROCK2) hallmarks the progression of neurodegenerative diseases. However, the molecular mechanisms underlying the regulation of ROCK2 expression are not clear and thus addressed in the current study. We generated a subacute model of Parkinson’s disease in mice with a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) method. The MPTP model was validated by impaired rotational behavior of the mice upon apomorphine exposure, astrocytic activation, and reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Moreover, MPTP induced increases in ROCK2 protein but not in ROCK2 mRNA. Further analysis showed that MPTP inhibited the expression of microRNA-291 (miR-291), which suppressed ROCK2 …mRNA via 3’-UTR-binding in neuronal cells to increase ROCK2 protein. Intracranial injection of miR-291 four days before MPTP alleviated the impaired rotational behavior of the mice upon apomorphine exposure, MPTP-induced astrocytic activation, and the reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Together, these data suggest that miR-291 has a protective role in neurodegeneration, likely through regulation of ROCK2. Show more

Keywords: MicroRNA-291, neurodegenerative disease, ROCK2

DOI: 10.3233/JAD-190832

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 815-822, 2019

Authors: Ji, Yangfei | Wang, Dan | Zhang, Boai | Lu, Hong

Article Type: Research Article

Abstract: Background: Parkinson’s disease (PD) is the second most prevalent progressive neurodegenerative disease, second only to Alzheimer’s disease, with motor disorders and cognitive impairment. Bergenin (Berg), extracted from the herb of Saxifrage stolonifera Curt. (Hu-Er-Cao), has anti-tumor, anti-inflammation, anti-oxidative stress, and neuroprotective properties. Objective: In this study, we wanted to investigate the effects of Berg on PD and the underlying mechanisms. Methods: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to introduce PD symptoms in mice. The expression levels of tyrosine hydroxylase, dopamine, and Iba-1 were examined. The levels of a series of inflammatory mediators were measured by qPCR. In …addition, the PI3K/Akt signaling pathway was investigated to illustrate the underlying mechanism. In vitro , PC12 cells subjected to lipopolysaccharide (LPS) were treated with Berg. Results: We found that MPTP injection introduced motor deficits, apoptosis of neurons and inflammation, as well as inhibited the PI3K/Akt signaling pathway. However, Berg treatment suppressed the MPTP-induced alterations. In vitro , Berg attenuated the cytotoxic effects on PC12 cells induced by the culture supernatants derived from LPS-induced microglial cells. Conclusion: Berg attenuated the PD symptoms via activating the PI3K/Akt signaling pathway in vivo and in vitro . Show more

Keywords: Alzheimer’s disease, bergenin, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), Parkinson’s disease, PI3K/Akt signaling pathway

DOI: 10.3233/JAD-190870

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 823-833, 2019

Authors: Nakanishi, Miharu | Yamasaki, Syudo | Nishida, Atsushi | Richards, Marcus

Article Type: Research Article

Abstract: Background: There is growing interest in public health strategies to modify dementia risk in midlife to reduce the burden of cognitive impairment in subsequent decades. Risk reduction messages should include key recommendations for women in response to the high prevalence of dementia observed in this population. Midlife is a critical period for dementia-related brain changes and psychosocial crises. Psychological well-being can improve resilience to crises, yet it is not well understood with respect to dementia risk reduction. Objective: This study aimed to examine the association between midlife psychological well-being and cognitive function in later life in women. …Methods: The study included 703 women from the British 1946 birth cohort in the Medical Research Council’s National Survey of Health and Development. Psychological well-being at 52 years was assessed using the Ryff Scales of Psychological Well-being over six dimensions: autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance. Cognitive function at 69 years was measured using the Addenbrooke’s Cognitive Examination, Third Edition. Results: After controlling for cognitive ability at eight years, educational attainment by 26 years, occupational attainment and marital status by 53 years, depression, smoking, and physical exercise at 60–64 years, there was a significant association between greater personal growth and lower self-acceptance at 52 years, and better cognition at 69 years. However, there was no association between cognition and the other four Ryff scales. Conclusion: Most aspects of midlife psychological well-being, except for personal growth and self-acceptance, were not prospectively associated with cognition. Show more

Keywords: Cohort studies, dementia, psychological well-being, risk factors, women

DOI: 10.3233/JAD-190590

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 835-843, 2019

Authors: Richards, Emma | Bayer, Antony | Tree, Jeremy J. | Hanley, Claire | Norris, Jade E. | Tales, Andrea

Article Type: Research Article

Abstract: In this study, reaction time (RT), intraindividual variability (IIV), and errors, and the effects of practice and processing load upon such function, were compared in patients with subcortical ischemic vascular cognitive impairment (SIVCI) [n  = 27] and cognitively healthy older adults (CH) [n  = 26]. Compared to CH aging, SIVCI was characterized by a profile of significantly slowed RT, raised IIV, and higher error levels, particularly in the presence of distracting stimuli, indicating that the integrity and/or accessibility of the additional functions required to support high processing load, serial search strategies, are reduced in SIVCI. Furthermore, although practice speeded RT in SIVCI, …unlike CH, practice did not lead to an improvement in IIV. This indicates that improvement in RT in SIVCI can in fact mask an abnormally high degree of IIV. Because IIV appears more related to disease, function, and health than RT, its status and potential for change may represent a particularly meaningful, and relevant, disease characteristic of SIVCI. Finally, a high level of within-group variation in the above measures was another characteristic of SIVCI, with such processing heterogeneity in patients with ostensibly the same diagnosis, possibly related to individual variation in pathological load. Detailed measurement of RT, IIV, errors, and practice effects therefore reveal a degree of functional impairment in brain processing not apparent by measuring RT in isolation. Show more

Keywords: Intra-individual variability, methodology, reaction time, subcortical ischemic vascular cognitive impairment

DOI: 10.3233/JAD-190889

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 845-857, 2019

Authors: Richards, Emma | Bayer, Antony | Hanley, Claire | Norris, Jade E. | Tree, Jeremy J. | Tales, Andrea

Article Type: Research Article

Abstract: Slowed behavioral reaction time is associated with pathological brain changes, including white matter lesions, the common clinical characteristic of subcortical ischemic vascular cognitive impairment (SIVCI). In the present study, reaction time (RT) employing Trails B of the Trail Making Test, with responses capped at 300 s, was investigated in SIVCI (n  = 27) compared to cognitively healthy aging (CH) (n  = 26). RT was significantly slowed in SIVCI compared to CH (Cohen’s d effect size = 1.26). Furthermore, failure to complete Trails B within 300 s was also a characteristic of SIVCI although some ostensibly cognitively healthy older adults also failed to complete within this time …limit. Within the SIVCI group, RT did not differ significantly with respect to whether the patients were classified as having moderate/severe or mild, periventricular white matter changes visible on their diagnostic CT/MRI scans. This, together with the high degree of overlap in RT between the two SIVCI subgroups, raises the possibility that using visible ratings scales in isolation may lead to the underestimation of disease level. Show more

Keywords: Methodology, reaction time, subcortical ischemic vascular cognitive impairment, Trail Making Test

DOI: 10.3233/JAD-190823

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 859-865, 2019

Authors: Yokokawa, Kazuki | Iwahara, Naotoshi | Hisahara, Shin | Emoto, Miho C. | Saito, Taro | Suzuki, Hiromi | Manabe, Tatsuo | Matsumura, Akihiro | Matsushita, Takashi | Suzuki, Syuuichirou | Kawamata, Jun | Sato-Akaba, Hideo | Fujii, Hirotada G. | Shimohama, Shun

Article Type: Research Article

Abstract: Mesenchymal stem cells (MSC) are increasingly being studied as a source of cell therapy for neurodegenerative diseases, and several groups have reported their beneficial effects on Alzheimer’s disease (AD). In this study using AD model mice (APdE9), we found that transplantation of MSC via the tail vein improved spatial memory in the Morris water maze test. Using electron paramagnetic resonance imaging to evaluate the in vivo redox state of the brain, we found that MSC transplantation suppressed oxidative stress in AD model mice. To elucidate how MSC treatment ameliorates oxidative stress, we focused on amyloid-β (Aβ) pathology and microglial …function. MSC transplantation reduced Aβ deposition in the cortex and hippocampus. Transplantation of MSC also decreased Iba1-positive area in the cortex and reduced activated ameboid shaped microglia. On the other hand, MSC transplantation accelerated accumulation of microglia around Aβ deposits and prompted microglial Aβ uptake and clearance as shown by higher frequency of Aβ-containing microglia. MSC transplantation also increased CD14-positive microglia in vivo , which play a critical role in Aβ uptake. To confirm the effects of MSC on microglia, we co-cultured the mouse microglial cell line MG6 with MSC. Co-culture with MSC enhanced Aβ uptake by MG6 cells accompanied by upregulation of CD14 expression. Additionally, co-culture of MG6 cells with MSC induced microglial phenotype switching from M1 to M2 and suppressed production of proinflammatory cytokines. These data indicate that MSC treatment has the potential to ameliorate oxidative stress through modification of microglial functions, thereby improving Aβ pathology in AD model mice. Show more

Keywords: Alzheimer’s disease, CD14, electron paramagnetic resonance imaging, mesenchymal stem cells, microglia, oxidative stress

DOI: 10.3233/JAD-190817

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 867-884, 2019

Authors: Lo Giudice, Maria | Mihalik, Balázs | Turi, Zsófia | Dinnyés, András | Kobolák, Julianna

Article Type: Research Article

Abstract: Despite numerous efforts and studies over the last three decades, Alzheimer’s disease (AD) remains a disorder not fully understood and incurable so far. Development of induced pluripotent stem cell (iPSC) technology to obtain terminally differentiated neurons from adult somatic cells revolutionized the study of AD, providing a powerful tool for modelling the disease and for screening candidate drugs. Indeed, iPSC reprogramming allowed generation of neurons from both sporadic and familial AD patients with the promise to recapitulate the early pathological mechanisms in vitro and to identify novel targets. Interestingly, NPS 2143, a negative allosteric modulator of the calcium sensing …receptor, has been indicated as a possible therapeutic for AD. In the present study, we assessed the potential of our iPSC-based familial AD cellular model as a platform for drug testing. We found that iPSC-derived neurons respond to treatment with γ -secretase inhibitor, modifying the physiological amyloid-β protein precursor (AβPP) processing and amyloid-β (Aβ) secretion. Moreover, we demonstrated the expression of calcium sensing receptor (CaSR) protein in human neurons derived from healthy and familial AD subjects. Finally, we showed that calcilytic NPS 2143 induced a changing of Aβ and sAβPPα secreted into conditioned media and modulation of CaSR and PSEN1 expression at the plasma membrane of AD neurons. Overall, our findings suggest that NPS 2143 affects important AD processes in a relevant in vitro system of familial AD. Show more

Keywords: Alzheimer’s disease, amyloid, calcium-sensing receptor, calcilytic, induced pluripotent stem cell-derived neurons, sAβPPα

DOI: 10.3233/JAD-190602

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 885-899, 2019

Authors: Geier, David A. | Kern, Janet K. | Homme, Kristin G. | Geier, Mark R.

Article Type: Research Article

Abstract:  Cognitive health is an emerging public health concern for the aging American population. Mercury (Hg) is a toxic element that can cause nervous system damage. This hypothesis-testing study evaluated the relationship between blood ethyl-Hg levels and cognitive decline in an older adult and elderly American population. A total of 1,821,663 weighted-persons between 60–80 years old with detectable blood ethyl-Hg levels within the 2011–2012 National Health and Nutritional Examination Survey were examined. Those persons with blood ethyl-Hg levels greater than the median were deemed the higher ethyl-Hg exposure group and those with ethyl-Hg levels less than the median were deemed the …lower ethyl-Hg exposure group. Three tests were utilized to measure cognitive function: 1) Consortium to Establish a Registry for Alzheimer’s Disease – Word List Learning (CERAD W-L) delayed recall test, 2) animal fluency test, and 3) Digit Symbol Substitution Test. Each cognitive test score was categorized as higher for those with scores greater than the median and lower for those with scores less than the median. Survey logistic regression modeling with covariates was used to analyze the data for the relationship between blood ethyl-Hg levels and cognitive function scores. Significantly increased risks for lower animal fluency test (odds ratio (OR) = 13.652, p  = 0.0029) and CERAD W-L delayed recall test (OR = 6.401, p  = 0.0433) scores were observed among the higher ethyl-Hg exposure group as compared to the lower ethyl-Hg exposure group. This study supports the hypothesis that increased ethyl-Hg exposure is associated with significant cognitive decline in older adult and elderly Americans. Show more

Keywords: Ethylmercury, merthiolate, methylmercury, thiomersal

DOI: 10.3233/JAD-190894

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 901-910, 2019

Authors: Boccardi, Virginia | Paolacci, Lucia | Remondini, Daniel | Giampieri, Enrico | Poli, Giulia | Curti, Nico | Cecchetti, Roberta | Villa, Alfredo | Ruggiero, Carmelinda | Brancorsini, Stefano | Mecocci, Patrizia

Article Type: Research Article

Abstract: Background: Elevated peripheral levels of different cytokines and chemokines in subjects with Alzheimer’s disease (AD), as compared with healthy controls (HC), have emphasized the role of inflammation in such a disease. Considering the cross-talking between the central nervous system and the periphery, the inflammatory analytes may provide utility as biomarkers to identify AD at earlier stages. Objective: Using an advanced statistical approach, we can discriminate the interactive network of cytokines/chemokines and propose a useful tool to follow the progression and evolution of AD, also in light of sex differences. Methods: A cohort of 289 old-age subjects …was screened for cytokine and chemokine profiling, measured in plasma, after a thorough clinical and neuropsychological evaluation. A custom algorithm based on Fisher linear discriminant analysis was applied to ascertain a classification signature able to discriminate HC from mild cognitive impairment (MCI) and AD. Results: We observed that a joint expression of three proteins (a “signature” composed by IFN-α 2, IL-1α , TNFα ) can discriminate HC from AD with an accuracy of 65.24%. Using this signature on MCI samples, 84.93% of them were classified as “non-HC”. Stratifying MCI samples by sex, we observed that 87.23% of women were classified as “non-HC”, and only 57.69% of males. Indeed, in a scatter plot of IFN-α 2 and IL-1α , the HC group was better separated from MCI and AD in women as compared with men. Conclusion: These findings suggest that AD is accompanied by a peripheral inflammatory response that can already be present in MCI subjects, thus providing a mean for detecting this at-risk status and allow an anticipated intervention. Show more

Keywords: Cytokines, dementia, inflammation, markers, sex

DOI: 10.3233/JAD-190480

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 911-918, 2019

Authors: Clark, Lindsay R. | Norton, Derek | Berman, Sara E. | Johnson, Sterling C. | Bendlin, Barbara B. | Wieben, Oliver | Turski, Patrick | Carlsson, Cynthia | Asthana, Sanjay | Gleason, Carey E. | Johnson, Heather M.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) has a higher prevalence among African Americans. Targeting cardiovascular and metabolic risk factors may be potential mechanisms to modify AD risk and address racial/ethnic disparities in AD dementia. Objective: This study investigated relationships among cardiovascular and metabolic risk factors, APOE genotype, AD biomarkers, and intracranial arterial blood flow in Whites and African Americans enriched for AD risk. Methods: 399 cognitively unimpaired adults from the Wisconsin Alzheimer’s Disease Research Center completed physical and neuroimaging examinations. A 4D Flow MRI sequence (phase-contrast vastly under sampled isotropic projection imaging) measured intracranial arterial flow in …the Circle of Willis. Linear mixed-effects regression models estimated relationships between risk factors and intracranial arterial flow and tested interactions with racial group, APOE genotype, and AD biomarkers, with separate models per risk factor. Results: Higher fasting glucose was associated with lower intracranial arterial flow; no additional relationships between flow and risk factors were observed. Main effects of racial group were observed, without an interaction, indicating lower flow in African Americans compared to Whites. In race-stratified analyses, higher glucose and triglycerides were associated with lower flow for African Americans, but not for Whites. No main effects or interactions among risk factors, APOE , or AD biomarkers, and flow were observed. Conclusion: Elevated fasting glucose and triglycerides were associated with lower intracranial arterial flow; these relationships were more prominent in African Americans. Targeting metabolic risk factors may impact intracranial arterial health. Additional research is needed to determine if this will impact disparities in dementia prevalence. Show more

Keywords: African Americans, aging, Alzheimer’s disease, Apolipoprotein E4, cerebrovascular circulation, glucose, metabolic syndrome, neuroimaging, risk factors

DOI: 10.3233/JAD-190645

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 919-929, 2019

Authors: Schelter, Bjoern O. | Shiells, Helen | Baddeley, Thomas C. | Rubino, Christopher M. | Ganesan, Harish | Hammel, Jeffrey | Vuksanovic, Vesna | Staff, Roger T. | Murray, Alison D. | Bracoud, Luc | Riedel, Gernot | Gauthier, Serge | Jia, Jianping | Bentham, Peter | Kook, Karin | Storey, John M.D. | Harrington, Charles R. | Wischik, Claude M.

Article Type: Research Article

Abstract: Background: Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials in mild to moderate Alzheimer’s disease (AD) comparing doses in the range 150–250 mg/day with 8 mg/day intended as a control. Objective: To determine how drug exposure is related to treatment response. Methods: A sensitive plasma assay for the drug was used in a population pharmacokinetic analysis of samples from 1,162 of the 1,686 patients who participated in either of the Phase III trials with available samples and efficacy outcome data. Results: There are steep concentration-response …relationships for steady state plasma levels in the range 0.3–0.8 ng/ml at the 8 mg/day dose. Using a threshold based on the lower limit of quantitation of the assay on Day 1, there are highly significant differences in cognitive decline and brain atrophy in patients with above threshold plasma levels, both for monotherapy and add-on therapy, but with effect sizes reduced by half as add-on. Plasma concentrations in the range 4–21 ng/ml produced by the high doses are not associated with any additional benefit. Conclusions: Hydromethylthionine has pharmacological activity on brain structure and function at the 8 mg/day dose as monotherapy or as add-on to symptomatic treatments. This combined with a plateau at higher doses is consistent with the lack of dose-response seen in the Phase III trials. Treatment benefit is predicted to be maximal at 16 mg/day as monotherapy. A placebo-controlled trial in mild/moderate AD is now ongoing to confirm efficacy at this dose. Show more

Keywords: Acetylcholinesterase inhibitor, Alzheimer’s disease, clinical trials, drug interaction, leucomethylthioninium, population pharmacokinetics, hydromethylthionine

DOI: 10.3233/JAD-190772

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 931-946, 2019

Authors: Huang, Nayan | Li, Wenjie | Rong, Xiangjiang | Champ, Mei | Wei, Lian | Li, Mo | Mu, Haiyan | Hu, Yueqing | Ma, Zongjuan | Lyu, Jihui

Article Type: Research Article

Abstract: Background: Tai Chi exercise is a non-pharmacological therapy that has received increased attention in recent years. A Tai Chi program has been specifically modified for older people with cognitive impairments by the research team. Objective: We aim to assess the effects of this Tai Chi program on mild dementia. Methods: Eighty older people with mild dementia were recruited and randomly assigned to a Tai Chi group or a control group. The Tai Chi group practiced the Tai Chi program three times a week for 10 months, while the control group continued receiving routine treatments. All participants …were assessed for cognitive function, behavior/mood, and activities of daily living at baseline, 5 months, and 10 months. Results: The Tai Chi group performed better than the control group. Repeated measures ANOVA revealed a significant group×time interaction in the Montreal Cognitive Assessment (MoCA). Further analysis of sub-items of the MoCA showed a significant time effect in naming and abstraction. It was statistically significant in both main effect of time and group×time interaction in the Neuropsychiatric Inventory (NPI) and Geriatric Depression Scale (GDS). Paired sample t test showed the Tai Chi group scored lower at 5 and 10 months in the NPI and at 10 months in the GDS compared with baseline. The Tai Chi group scored lower than the control group at 10 months in the NPI and GDS. Conclusion: The results suggest this Tai Chi program may help improve cognitive function and mental well-being for older adults with mild dementia. Show more

Keywords: Behavioral and psychological symptoms, cognitive function, dementia, depressive mood, Tai Chi

DOI: 10.3233/JAD-190487

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 947-956, 2019

Authors: Fuchsberger, Tanja | Yuste, Raquel | Martinez-Bellver, Sergio | Blanco-Gandia, Mari-Carmen | Torres-Cuevas, Isabel | Blasco-Serra, Arantxa | Arango, Román | Miñarro, Jose | Rodríguez-Arias, Marta | Teruel-Marti, Vicent | Lloret, Ana | Viña, Jose

Article Type: Research Article

Abstract: Glutamate excitotoxicity has long been related to Alzheimer’s disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, …we observed a decrease in the AMPA receptor subunit GluA1 and they had impaired long-term potentiation. The Hebb-Williams Maze revealed that they had memory deficits. We show here for the first time that oral MSG supplementation can accelerate AD-like pathophysiology in a mouse model of AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, glutamate excitotoxicity, long-term potentiation, memory, p-tau

DOI: 10.3233/JAD-190274

Citation: Journal of Alzheimer's Disease, vol. 72, no. 3, pp. 957-975, 2019