Journal of Alzheimer's Disease - Volume 87, issue 4

Authors: Libon, David J. | Swenson, Rod | Lamar, Melissa | Price, Catherine C. | Baliga, Ganesh | Pascual-Leone, Alvaro | Au, Rhoda | Cosentino, Stephanie | Andersen, Stacy L.

Article Type: Review Article

Abstract: Neuropsychological assessment using the Boston Process Approach (BPA) suggests that an analysis of the strategy or the process by which tasks and neuropsychological tests are completed, and the errors made during test completion convey much information regarding underlying brain and cognition and are as important as overall summary scores. Research over the last several decades employing an analysis of process and errors has been able to dissociate between dementia patients diagnosed with Alzheimer’s disease, vascular dementia associated with MRI-determined white matter alterations, and Parkinson’s disease; and between mild cognitive impairment subtypes. Nonetheless, BPA methods can be …labor intensive to deploy. However, the recent availability of digital platforms for neuropsychological test administration and scoring now enables reliable, rapid, and objective data collection. Further, digital technology can quantify highly nuanced data previously unobtainable to define neurocognitive constructs with high accuracy. In this paper, a brief review of the BPA is provided. Studies that demonstrate how digital technology translates BPA into specific neurocognitive constructs using the Clock Drawing Test, Backward Digit Span Test, and a Digital Pointing Span Test are described. Implications for using data driven artificial intelligence-supported analytic approaches enabling the creation of more sensitive and specific detection/diagnostic algorithms for putative neurodegenerative illness are also discussed. Show more

Keywords: Backward digit span test, Boston Process Approach, clock drawing test, cognitive vital signs, digit span test, digital assessment, digital neuropsychological assessment

DOI: 10.3233/JAD-220096

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1419-1432, 2022

Authors: Salehipour, Arash | Bagheri, Motahareh | Sabahi, Mohammadmahdi | Dolatshahi, Mahsa | Boche, Delphine

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-β (Aβ), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach. Considering the distinction between added and combination therapies, one can conclude that most trials fall under the category of added therapies. For combination therapy to have an actual impact …on the course of AD, it is likely necessary to target multiple mechanisms including but not limited to Aβ and tau pathology. Several challenges have to be addressed regarding combination therapy, including choosing the correct agents, the best time and stage of AD to intervene, designing and providing proper protocols for clinical trials. This can be achieved by a cooperation between the pharmaceutical industry, academia, private research centers, philanthropic institutions, and the regulatory bodies. Based on all the available information, the success of combination therapy to tackle complicated disorders such as cancer, and the blueprint already laid out on how to implement combination therapy and overcome its challenges, an argument can be made that the field has to move cautiously but quickly toward designing new clinical trials, further exploring the pathological mechanisms of AD, and re-examining the previous studies with combination therapies so that effective treatments for AD may be finally found. Show more

Keywords: Alzheimer’s disease, clinical trials, combination therapy, treatment

DOI: 10.3233/JAD-215680

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1433-1449, 2022

Authors: Preethy, Senthilkumar | Ranganathan, Natarajan | Raghavan, Kadalraja | Dedeepiya, Vidyasagar Devaprasad | Ikewaki, Nobunao | Abraham, Samuel J.K.

Article Type: Review Article

Abstract: A new paradigm of cell therapy-based approaches as a solution to several diseases caused by damage or loss of cells/tissues leading to organ failure heralded the birth of a new branch in medicine called regenerative medicine (RM), which was further fueled by in vitro cell expansion and tissue engineering (TE) technologies, including the ability to grow embryonic stem cells, induce pluripotent stem cells, and so on. RM addresses organ failure by repair, regeneration, or restoration, rejuvenation using cells, stem cells, or progenitor cells as tools having added cell-derived products also as a tool, and extracellular matrix component–based support, either …direct or indirect (e.g., matrix induced autologous chondrocyte implantation) using scaffolds. Now, the main objective of RM is to solve the functional loss of cells that have evolved from cells as tools to cell-derived factors and scaffolds per se as tools. In this context, an important yet indispensable group of cells that constitute the major portion of the human body in terms of the number of cells having several essential roles to play, both directly and indirectly, starting from digestion and the immune system to the growing evidence of influencing neuronal function, aging, and carcinogenesis has been ignored. We would like to focus on these in this review as they should essentially be considered as a tool of RM, especially for neurological disorders for their vital role. What we are indicating is the second genome or the gut microbiome. Show more

Keywords: Cells, gut microbiota, paracrine, regenerative medicine, scaffolds, second genome, tools

DOI: 10.3233/JAD-220313

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1451-1460, 2022

Authors: Cato, Sarah | Ramer, Stephanie | Hajjar, Ihab | Kulshreshtha, Ambar

Article Type: Short Communication

Abstract: This study investigated Alzheimer’s disease (AD) mortality trends by urbanization level and geographical location in the U.S. The CDC’s WONDER database was used to investigate AD mortality from 1999–2019 stratified by urbanization level, census division, race, and sex. Data showed that while AD mortality increased across the U.S., rural areas, particularly in the South, had higher mortality compared to urban counterparts. AD mortality was higher among the female and White population. Data suggested that the urban-rural discrepancy is widening over time. Identifying health disparities underlying the urban-rural discrepancy in AD mortality is critical for allocating social and public health resources.

Keywords: Alzheimer’s disease, census, healthcare disparities, mortality, race, rural health, sex, urban health, urbanization

DOI: 10.3233/JAD-215586

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1461-1466, 2022

Authors: Valletta, Martina | Canevelli, Marco | D’Antonio, Fabrizia | Trebbastoni, Alessandro | Talarico, Giuseppina | Campanelli, Alessandra | Sepe Monti, Micaela | Di Vita, Antonella | Salati, Emanuela | Imbriano, Letizia | Margiotta, Roberta | Barbetti, Sonia | Diana, Sofia | Buscarnera, Simona | Toccaceli Blasi, Marco | Salzillo, Martina | Pugliese, Giuseppe | Vanacore, Nicola | Bruno, Giuseppe

Article Type: Short Communication

Abstract: This study aimed to explore the prevalence and safety of SARS-CoV-2 vaccination in individuals with dementia. Patients with mild cognitive impairment or dementia were recruited at a tertiary memory clinic, from March 15 to September 15, 2021. Information on COVID-19 vaccination and adverse events experienced after vaccine administration were collected from caregivers. Two-hundred-seventy subjects were finally recruited. Among them, 253 (93.7%) had received the vaccine and only 69 (27.3%) experienced adverse events. Cognitive and behavioral changes following immunization were only rarely reported. COVID-19 vaccination is safe and well-tolerated in patients with cognitive impairment who should be prioritized in the vaccination …campaign. Show more

Keywords: Cognitive impairment, COVID-19, dementia, SARS-CoV-2, vaccination, vaccines

DOI: 10.3233/JAD-220077

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1467-1474, 2022

Authors: Bose, Arpita | Dutta, Manaswita | Dash, Niladri S. | Nandi, Ranita | Dutt, Aparna | Ahmed, Samrah

Article Type: Short Communication

Abstract: Features of linguistic impairment in Alzheimer’s disease (AD) are primarily derived from English-speaking patients. Little is known regarding such deficits in linguistically diverse speakers with AD. We aimed to detail linguistic profiles (speech rate, dysfluencies, syntactic, lexical, morphological, semantics) from two connected speech tasks–Frog Story and picture description–in Bengali-speaking AD patients. The Frog Story detected group differences on all six linguistic levels, compared to only three with picture description. Critically, Frog Story captured the language-specific differences between the groups. Careful consideration should be given to the choice of connected speech tasks for dementia diagnosis in linguistically diverse populations.

Keywords: Alzheimer’s disease, Bengali, connected speech, picture description, semantic, speech analysis, story narration

DOI: 10.3233/JAD-220166

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1475-1481, 2022

Authors: Bommarito, Giulia | Garibotto, Valentina | Frisoni, Giovanni B. | Ribaldi, Federica | Stampacchia, Sara | Assal, Frédéric | Armand, Stéphane | Allali, Gilles | Griffa, Alessandra

Article Type: Short Communication

Abstract: We conducted a cross-sectional pilot study to explore the biological substrate of the Motoric Cognitive Risk (MCR) syndrome in a Memory Clinic cohort, using a multimodal imaging approach. Twenty participants were recruited and classified as MCR+/−. Amyloid- and tau-PET uptakes, temporal atrophy, white matter hyperintensities, lateral ventricular volume (LVV), and diffusion tensor parameters were compared between groups. No significant differences were found in imaging features related to Alzheimer’s disease or gross vascular damage. MCR+ patients had increased LVV and altered diffusion parameters in the superior corona radiata. Ventricular enlargement and microstructural damage of the surrounding white matter tracts could contribute …to MCR pathophysiology. Show more

Keywords: Alzheimer’s disease, diffusion MRI, gait disorder, lateral ventricles, vascular dementia

DOI: 10.3233/JAD-215461

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1483-1490, 2022

Authors: LoBue, Christian | Kelley, Brendan J. | Hart Jr., John | Helphrey, Jessica | Schaffert, Jeff | Cullum, C. Munro | Peters, Matthew E. | Douglas, Peter M. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: Few studies have examined an association between mild traumatic brain injury (mTBI) and Alzheimer’s disease (AD). For this reason, we compared an AD dementia group with an mTBI history (n  = 10) to a matched AD control group (n  = 20) on measures of cognitive function, cerebral glucose metabolism, and markers of amyloid and tau deposition. Only a trend and medium-to-large effect size for higher phosphorylated and total tau was identified for the mTBI group. A history of mTBI may be associated with greater tau in AD, indicating a potential pathway for increasing risk for AD, though further evaluation with larger samples …is needed. Show more

Keywords: Biomarkers, concussion, dementia, neurodegeneration, risk factor, tau formation, traumatic brain injury

DOI: 10.3233/JAD-220112

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1491-1496, 2022

Authors: Orive, Gorka | Lopera, Francisco | Carro, Eva

Article Type: Editorial

DOI: 10.3233/JAD-220144

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1497-1501, 2022

Authors: Kalari, Mohadeseh | Abbasi, Zeinab | Shasaltaneh, Marzieh Dehghan | Khaleghian, Ali | Moosavi-Nejad, Zahra

Article Type: Research Article

Abstract: Background: Acetylcholinesterase (AChE) regulates the transmission of neural messages by hydrolyzing acetylcholine in synaptic spaces. Objective: The effects of many AChE inhibitors have been evaluated in the treatment of Alzheimer’s disease, but the present study examined a synthetic complex containing cobalt (SC) for the first time in the field of enzyme activity to evaluate enzyme inhibitory function. Methods: Ellman’s test was applied. AChE function was assessed in the presence of SC through docking and molecular dynamics analyses. The second structure of AChE was studied through circular dichroism (CD) spectroscopy. Results: Several enzymatic methods …were utilized for the kinetics of AChE, which indicated the non-Michaelis and positive homotropic behavior of AChE in the absence of inhibitors (Hill coefficient = 1.33). However, the existence of inhibitors did not eliminate this homotropic state, and even AChE had a more sigmoidal shape than the galantamine at the presence of SC. Based on the CD spectroscopy results, AChE structure changed in the existence of inhibitors and substrates. Bioinformatics analysis revealed SC bonding to the channel of active site AChE. The number of hydrogen bonds was such that the flexibility of the enzyme protein structure due to inhibitor binding reduced AChE function. Conclusion: The results reflected that AChE exhibited a non-Michaelis and positive homotropic behavior, leading to a more inhibitory effect on the SC than the galantamine. The positive homotropic behavior of AChE was intensified due to the alteration in AChE protein structure by binding SC to hydrophobic region in the active site pathway and impressing Trp84. Show more

Keywords: Acetylcholinesterase, Alzheimer’s disease, enzyme kinetics, galantamine, inhibitor

DOI: 10.3233/JAD-215588

Citation: Journal of Alzheimer's Disease, vol. 87, no. 4, pp. 1503-1516, 2022