Journal of Alzheimer's Disease - Volume 84, issue 3

Authors: Pacheco-Herrero, Mar | Soto-Rojas, Luis O. | Reyes-Sabater, Heidy | Garcés-Ramirez, Linda | de la Cruz López, Fidel | Villanueva-Fierro, Ignacio | Luna-Muñoz, José

Article Type: Review Article

Abstract: Neurodegenerative diseases called tauopathies, such as Alzheimer’s disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson’s disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient’s cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development …of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, neural stem cells, neurodegeneration, stem cells, tau protein, therapy

DOI: 10.3233/JAD-200863

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 917-935, 2021

Authors: Song, Xi-Jun | Zhou, He-Yan | Sun, Yu-Ying | Huang, Han-Chang

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disorder in the central nervous system, and this disease is characterized by extracellular senile plaques and intracellular neurofibrillary tangles. Amyloid-β (Aβ) peptide is the main constituent of senile plaques, and this peptide is derived from the amyloid-β protein precursor (AβPP) through the successive cleaving by β-site AβPP-cleavage enzyme 1 (BACE1) and γ-secretase. AβPP undergoes the progress of post-translational modifications, such as phosphorylation and glycosylation, which might affect the trafficking and the cleavage of AβPP. In the recent years, about 10 phosphorylation sites of AβPP were identified, and they play complex roles in glycosylation modification …and cleavage of AβPP. In this article, we introduced the transport and the cleavage pathways of AβPP, then summarized the phosphorylation and glycosylation sites of AβPP, and further discussed the links and relationship between phosphorylation and glycosylation on the pathways of AβPP trafficking and cleavage in order to provide theoretical basis for AD research. Show more

Keywords: Alzheimer’s disease, amyloid-β protein precursor, protein glycosylation, protein phosphorylation

DOI: 10.3233/JAD-210337

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 937-957, 2021

Authors: Wang, Zan | Zhang, Zhengsheng | Xie, Chunming | Shu, Hao | Liu, Duan | Zhang, Zhijun

Article Type: Short Communication

Abstract: Based on whole-brain gray matter volume (GMV), we used relevance vector regression to predict the Rey’s Auditory Verbal Learning Test Delayed Recall (AVLT-DR) scores of individual amnestic mild cognitive impairment (aMCI) patient. The whole-brain GMV pattern could significantly predict the AVLT-DR scores (r  = 0.54, p  < 0.001). The most important GMV features mainly involved default-mode (e.g., posterior cingulate gyrus, angular gyrus, and middle temporal gyrus) and limbic systems (e.g., hippocampus and parahippocampal gyrus). Therefore, our results provide evidence supporting the idea that the episodic memory deficit in aMCI patients is associated with disruption of the default-mode and limbic systems.

Keywords: Amnestic mild cognitive impairment, episodic memory, gray matter volume, machine learning, relevance vector regression

DOI: 10.3233/JAD-210579

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 959-964, 2021

Authors: Pandey, Janardan P. | Namboodiri, Aryan M. | Nietert, Paul J. | Barnes, Lisa L. | Bennett, David A.

Article Type: Short Communication

Abstract: We investigated whether FCGRIIB (rs1050501 C/T) and PILRA (rs1859788 A/G) genotypes contributed to the development of Alzheimer’s disease (AD). We genotyped 209 African American (AA) and 638 European American (EA) participants for the FCGRIIB and PILRA alleles. In the AA cohort, subjects homozygous for the C allele of FCGRIIB were more than 4 times as likely to develop AD as those homozygous for the alternative T allele. This SNP also interacted with PILRA : participants who were the carriers of the FCGRIIB C allele and PILRA A allele were 3 times as likely to …develop AD as those who lacked these alleles. Show more

Keywords: Amyloid-β, FCGRIIB, neurotoxicity, PILRA

DOI: 10.3233/JAD-215174

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 965-968, 2021

Authors: Kurkinen, Markku | Tran, Lloyd

Article Type: Editorial

DOI: 10.3233/JAD-215105

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 969-971, 2021

Authors: Farfel, Jose M. | Barnes, Lisa L. | Capuano, Ana | Sampaio, Maria Carolina de Moraes | Wilson, Robert S. | Bennett, David A.

Article Type: Research Article

Abstract: Background: Self-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without dementia. Objective: Here, we examine the association of discrimination with dementia and cognitive impairment in racially diverse older Brazilians. Methods: We included 899 participants 65 years or older (34.3% Black) from the Pathology, Alzheimer’s and Related Dementias Study (PARDoS), a community-based study of aging and dementia. A structured interview with informants of the deceased was conducted. The interview included the Clinical Dementia Rating (CDR) Scale for the diagnosis of dementia and cognitive impairment …proximate to death and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a second measure of cognitive impairment. Informant-reported discrimination was assessed using modified items from the Major and Everyday Discrimination Scales. Results: Discrimination was reported by informants of 182 (20.2%) decedents and was more likely reported by informants of Blacks than Whites (25.3% versus 17.6%, p  = 0.006). Using the CDR, a higher level of informant-reported discrimination was associated with higher odds of dementia (OR: 1.24, 95% CI 1.08 –1.42, p  = 0.002) and cognitive impairment (OR: 1.21, 95% CI: 1.06 –1.39, p  = 0.004). Similar results were observed using the IQCODE (estimate: 0.07, SE: 0.02, p  = 0.003). The effects were independent of race, sex, education, socioeconomic status, major depression, neuroticism, or comorbidities. Conclusion: Higher level of informant-reported discrimination was associated with higher odds of dementia and cognitive impairment in racially diverse older Brazilians. Show more

Keywords: Cognitive impairment, dementia, discrimination, race

DOI: 10.3233/JAD-201436

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 973-981, 2021

Authors: Tian, Tian | Qin, Xin | Wang, Yali | Shi, Yan | Yang, Xin

Article Type: Research Article

Abstract: Background: 40 Hz light flicker is a well-known non-invasive treatment that is thought to be effective in treating Alzheimer’s disease. However, the effects of 40 Hz visual stimulation on neural networks, synaptic plasticity, and learning and memory in wild-type animals remain unclear. Objective: We aimed to explore the impact of 40 Hz visual stimulation on synaptic plasticity, place cell, and learning and memory in wild-type mice. Methods: c-Fos+ cell distribution and in vivo electrophysiology was used to explore the effects of 40 Hz chronic visual stimulation on neural networks and neuroplasticity in wild-type mice. The character of c-Fos+ …distribution in the brain and the changes of corticosterone levels in the blood were used to investigate the state of animal. Place cell analysis and novel location test were utilized to examine the effects of 40 Hz chronic visual stimulation on learning and memory in wild-type mice. Results: We found that 40 Hz light flicker significantly affected many brain regions that are related to stress. Also, 40 Hz induced gamma enrichment within 15 min after light flickers and impaired the expression of long-term potentiation (LTP), while facilitated the expression of long-term depression (LTD) in the hippocampal CA1. Furthermore, 40 Hz light flicker enhanced the expression of corticosterone, rendered well-formed place cells unstable and improved animal’s learning and memory in novel local recognition test, which could be blocked by pre-treatment with the LTD specific blocker Glu2A-3Y. Conclusion: These finding suggested that 40 Hz chronic light flicker contains stress effects, promoting learning and memory in wild-type mice via LTD. Show more

Keywords: 40 Hz, Alzheimer’s disease, gamma, stress, synaptic plasticity

DOI: 10.3233/JAD-215212

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 983-993, 2021

Authors: Jeon, So Yeon | Kim, Jeong Lan

Article Type: Research Article

Abstract: Background: Being a spousal caregiver (SCG) for a patient with cognitive impairment is well known to be associated with increased risk for dementia and cognitive decline. Objective: This study examined the impact of the care-recipient’s cognitive status on lifestyle factors influencing cognitive decline in SCGs, focusing on nutritional status and blood biomarkers. Methods: Fifty-one SCGs participated (mean age 73.5±7.0 years) in this study. All participants underwent clinical assessment including the Mini Nutritional Assessment (MNA), Geriatric Depression Scale, Pittsburgh Sleep Quality Index, and International Physical Activity Questionnaire to evaluate lifestyle factors, and the Mini-Mental …State Examination to assess global cognition. Also, nutritional blood biomarkers were measured. Results: SCGs caring for a demented spouse showed significantly higher depression scores (t  = –3.608, p  = 0.001) and malnutrition risk (t  = 2.894, p  = 0.006) compared to those caring for a non-demented spouse. Decreased care recipients’ cognition was significantly correlated with higher GDS (β= –0.593, t  = –4.471, p  < 0.001) and higher MNA scores (β= 0.315, t  = 2.225, p  = 0.031) and lower level of high-density lipoprotein (HDL) cholesterol (β= 0.383, t  = 2.613, p  = 0.012) in their SCGs. Gender had moderating effects on association of care-recipients’ cognition with sleep quality (B[SE]  = 0.400[0.189], p  = 0.041) and HDL cholesterol (B[SE]  = –1.137[0.500], p  = 0.028) among SCGs. Poorer care-recipient’s cognition was associated with worse sleep quality and low HDL cholesterol among wives but not husband caregivers. Conclusion: This study provides substantial evidence that SCGs are at risk for depression and malnutrition, which can further affect cognitive decline. As such, these factors should be well assessed and monitored among SCGs for patient with cognitive impairment. Show more

Keywords: Dementia, depression, HDL cholesterol, malnutrition, spousal caregiver

DOI: 10.3233/JAD-210694

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 995-1003, 2021

Authors: Stanitsa, Evangelia | Economou, Alexandra | Beratis, Ion | Kontaxopoulou, Dionysia | Fragkiadaki, Stella | Papastefanopoulou, Vicky | Pavlou, Dimosthenis | Papantoniou, Panagiotis | Kroupis, Christos | Papatriantafyllou, John | Stefanis, Leonidas | Yannis, George | Papageorgiou, Sokratis G.

Article Type: Research Article

Abstract: Background: The driving behavior of patients with mild Alzheimer’s disease dementia (ADD) and patients with mild cognitive impairment (MCI) is frequently characterized by errors. A genetic factor affecting cognition is apolipoprotein E4 (APOE4 ), with carriers of APOE4 showing greater episodic memory impairment than non-carriers. However, differences in the driving performance of the two groups have not been investigated. Objective: To compare driving performance in APOE4 carriers and matched non-carriers. Methods: Fourteen APOE4 carriers and 14 non-carriers with amnestic MCI or mild ADD underwent detailed medical and neuropsychological assessment and participated in a …driving simulation experiment, involving driving in moderate and high traffic volume in a rural environment. Driving measures were speed, lateral position, headway distance and their SDs, and reaction time. APOE was genotyped through plasma samples. Results: Mixed two-way ANOVAs examining traffic volume and APOE4 status showed a significant effect of traffic volume on all driving variables, but a significant effect of APOE4 on speed variability only. APOE4 carriers were less variable in their speed than non-carriers; this remained significant after a Bonferroni correction. To further examine variability in the driving performance, coefficients of variation (COV) were computed. Larger headway distance COV and smaller lateral position COV were observed in high compared to moderate traffic. APOE4 carriers had smaller speed COV compared to non-carriers. Conclusion: The lower speed variability of APOE4 carriers in the absence of neuropsychological test differences indicates reduced speed adaptations, possibly as a compensatory strategy. Simulated driving may be a sensitive method for detecting performance differences in the absence of cognitive differences. Show more

Keywords: Alzheimer’s disease dementia, APOE4, driving behavior, driving simulator, mild cognitive impairment

DOI: 10.3233/JAD-210622

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 1005-1014, 2021

Authors: Largent, Emily A. | Bhardwaj, Twisha | Abera, Maramawit | Stites, Shana D. | Harkins, Kristin | Lerner, Alan J. | Bradbury, Angela R. | Karlawish, Jason

Article Type: Research Article

Abstract: Background: Current practice guidelines recommend against Apolipoprotein E (APOE ) testing. However, advances in Alzheimer’s disease (AD) research and care may soon change this. Objective: To examine longitudinally the experience of learning an APOE result and, if an ɛ4 carrier, taking a disease-specific treatment to reduce one’s risk of AD. Methods: Fifty ɛ4 carriers and 20 non-carriers completed semi-structured interviews 3 months and 15 months after APOE disclosure. Results: Individuals generally understand their APOE results. While non-carriers felt relief, ɛ4 carriers often described themselves as disappointed by …their result but nevertheless glad to know. Carriers expressed concerns about stigma and discrimination, including in the workplace. Carriers adopted new health behaviors at higher rates than non-carriers and revised their future plans to account for their increased risk of AD. Individuals participating in research were hopeful that their participation would help them or others; individuals who learned they were at increased risk for AD but who could not participate in research were disappointed. Conclusion: Providers disclosing APOE results should be sensitive to how APOE results shape emotions, self-perceptions, and attitudes about memory; raise concerns about stigma and discrimination in personal and professional relationships; influence health behaviors and decision-making; and can have follow-on effects on family members. Show more

Keywords: Amyloid, apolipoprotein E, dementia, genetic counseling, genetic testing, risk

DOI: 10.3233/JAD-210675

Citation: Journal of Alzheimer's Disease, vol. 84, no. 3, pp. 1015-1028, 2021