Journal of Alzheimer's Disease Reports - Volume 5, issue 1

Authors: Panegyres, Peter K.

Article Type: Research Article

Abstract: Background: Dementia is a major global health problem and the search for improved therapies is ongoing. The study of young onset dementia (YOD)—with onset prior to 65 years—represents a challenge owing to the variety of clinical presentations, pathology, and gene mutations. The advantage of the investigation of YOD is the lack of comorbidities that complicate the clinical picture in older adults. Here we explore the origins of YOD. Objective: To define the clinical diversity of YOD in terms of its demography, range of presentations, neurological examination findings, comorbidities, medical history, cognitive findings, imaging abnormalities both structural and functional, …electroencephagraphic (EEG) data, neuropathology, and genetics. Methods: A prospective 20-year study of 240 community-based patients referred to specialty neurology clinics established to elucidate the nature of YOD. Results: Alzheimer’s disease (AD; n  = 139) and behavioral variant frontotemporal (bvFTD; n  = 58) were the most common causes with a mean age of onset of 56.5 years for AD (±1 SD 5.45) and 57.1 years for bvFTD (±1 SD 5.66). Neuropathology showed a variety of diagnoses from multiple sclerosis, Lewy body disease, FTD-MND, TDP-43 proteinopathy, adult-onset leukoencephalopathy with axonal steroids and pigmented glia, corticobasal degeneration, unexplained small vessel disease, and autoimmune T-cell encephalitis. Non-amnestic forms of AD and alternative forms of FTD were discovered. Mutations were only found in 11 subjects (11/240 = 4.6%). APOE genotyping was not divergent between the two populations. Conclusion: There are multiple kinds of YOD, and most are sporadic. These observations point to their stochastic origins. Show more

Keywords: Neurodegeneration, sporadic onset, stochasticity, young onset dementia

DOI: 10.3233/ADR-210309

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 663-679, 2021

Authors: Ambegaonkar, Anjay | Ritchie, Craig | de la Fuente Garcia, Sofia

Article Type: Review Article

Abstract: Background: Communication difficulties are one of the primary symptoms associated with dementia, and mobile applications have shown promise as tools for facilitating communication in patients with dementia (PwD). The literature regarding mobile health (mHealth) applications, especially communications-based mHealth applications, is limited. Objective: This review aims to compile the existing literature on communications-based mobile applications regarding dementia and assess their opportunities and limitations. A PICO framework was applied with a Population consisting of PwD, Interventions consisting of communication technology, focusing primarily on mobile applications, Comparisons between patient well-being with and without technological intervention, and Outcomes that vary but can …include usability of technology, quality of communication, and user acceptance. Methods: Searches of PubMed, IEEE XPLORE, and ACM Digital Library databases were conducted to establish a comprehensive understanding of the current literature on dementia care as related to 1) mobile applications, 2) communication technology, and 3) communications-based mobile applications. Applying certain inclusion and exclusion criteria, yielded a set of articles (n  = 11). Results: The literature suggests that mobile applications as tools for facilitating communication in PwD are promising. Mobile applications are not only feasible socially, logistically, and financially, but also produce meaningful communication improvements in PwD and their caregivers. However, the number of satisfactory communications-based mobile applications in the mHealth marketplace and their usability is still insufficient. Conclusion: Despite favorable outcomes, more research involving PwD using these applications are imperative to shed further light on their communication needs and on the role of mHealth. Show more

Keywords: Caregiver, communication, dementia, mobile applications

DOI: 10.3233/ADR-200259

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 681-692, 2021

Authors: Hakim, Md A. | Behringer, Erik J.

Article Type: Research Article

Abstract: Background: As the sixth-leading cause of death in the United States, Alzheimer’s disease (AD) entails deteriorating endothelial control of blood flow throughout the brain. In particular, reduced inward-rectifying K+ (KIR ) channel function in animal models of aging and AD compromises endothelial function and optimal perfusion of brain parenchyma. Deficient endothelial KIR channels may result from aberrant interaction with plasma membrane cholesterol as a primary regulator of membrane fluidity and ion channels. Objective: We tested the hypothesis that mild methyl-β-cyclodextrin (MβCD) treatment to reduce membrane cholesterol may restore endothelial KIR channel function in brain endothelium …of old AD mice. Methods: Membrane potential was continuously measured in isolated endothelial tubes from posterior cerebral arteries of young (1 to 3 months) and old (16 to 19 months) female 3xTg-AD mice before and after mild treatment with the cholesterol-removing agent MβCD (1 mmol/L). Elevated extracellular potassium ([K+ ]E ; 15 mmol/L) and NS309 (1μmol/L) activated KIR and Ca2+ -activated K+ (SKCa /IKCa ) channels respectively before and after MβCD treatment. Results: SKCa /IKCa channel function for producing hyperpolarization remained stable regardless of age group and MβCD treatment (Δ Vm : ∼–33 mV). However, as deficient during AD, KIR channel function was restored (Δ Vm : –9±1 mV) versus pre-MβCD conditions (–5±1 mV); a progressive effect that reached –14±1 mV hyperpolarization at 60 min following MβCD washout. Conclusion: In female animals, MβCD treatment of brain endothelium selectively restores KIR versus SKCa /IKCa channel function during AD. Thus, the endothelial cholesterol-KIR channel interface is a novel target for ameliorating perfusion of the AD brain. Show more

Keywords: Alzheimer’s disease, brain endothelium, cholesterol, K+ ion channels

DOI: 10.3233/ADR-210016

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 693-703, 2021

Authors: Yunusa, Ismaeel | Alsahali, Saud | Rane, Amey | Eguale, Tewodros

Article Type: Research Article

Abstract: Background: Pharmacological treatment of Alzheimer’s disease (AD) involves symptomatic improvement of cognition using cholinesterase inhibitors (ChEIs) and memantine. The cost-effectiveness of these medications will guide decision-makers in making judicious use of scarce healthcare resources, particularly during the advanced disease stages. Objective: To evaluate the cost-effectiveness of ChEIs, memantine, and ChEI-memantine combinations in persons with moderate-to-severe AD from the US healthcare perspective. Methods: This pharmacoeconomic evaluation study used a state-transition Markov cohort model to simulate the costs and effectiveness of ChEI-memantine combinations compared with monotherapies of ChEI (donepezil, galantamine and rivastigmine) and memantine in persons with moderate-to-severe …AD over a lifetime horizon with a 1-year cycle length. We estimated expected quality-adjusted life-years (QALYs), costs (in 2020 $US), net monetary benefits, and incremental cost-effectiveness ratios (ICERs). We discounted future costs and QALYs at the rate of 3%. Results: In this study, donepezil monotherapy, galantamine-memantine combination, and rivastigmine transdermal patch formed the cost-effectiveness frontier. Findings suggests that rivastigmine transdermal patch is the optimal treatment strategy at a willingness-to-pay (WTP) threshold of $150,000/QALY (ICER = $93,307/QALY [versus donepezil monotherapy]). Results across subgroups by age and sex also suggest that the rivastigmine transdermal patch is the optimal treatment strategy with the highest net benefit. Conclusion: From the US healthcare perspective, we found that, for persons with moderate-to-severe AD at a WTP threshold of $150,000/QALY, the rivastigmine transdermal patch is the most cost-effective pharmacological treatment option. Given that the transdermal patch is a preferred route of administration for persons with AD and their caregivers due to its convenience, our findings provide additional incentives for its use. Show more

Keywords: Alzheimer’s disease, cholinesterase inhibitors, cost-effectiveness analysis, donepezil, memantine, quality-adjusted life years, rivastigmine

DOI: 10.3233/ADR-210307

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 705-713, 2021

Authors: Giannouli, Vaitsa | Tsolaki, Magda

Article Type: Short Communication

Abstract: Neuropsychological assessment in amnestic mild cognitive impairment (aMCI) becomes complicated when education-literacy is taken into consideration. This study sought to explore the potential influence of literacy/illiteracy and education on financial capacity in patients with multiple-domain aMCI. Six groups consisting of aMCI (illiterate-no formal education, literate with low education, and literate with high education) and non-demented controls were examined. Literacy has an effect on financial capacity, as the illiterate aMCI group alone had the lowest scores in a financial capacity test resembling the performance of patients with mild Alzheimer’s disease. In controls there was a similar pattern, but all three healthy …groups regardless of education scored above the cut-off score for incapacity. Show more

Keywords: Amnestic mild cognitive impairment, financial capacity, literacy/illiteracy

DOI: 10.3233/ADR-210033

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 715-719, 2021

Authors: Elwishahy, Abdelrahman | Antia, Khatia | Bhusari, Sneha | Ilechukwu, Nkorika Chiamaka | Horstick, Olaf | Winkler, Volker

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a chronic neurodegenerative disease that accounts for more than 50% of all dementia cases worldwide. There is wide consensus on the risk factors of AD; however, a clear etiology remains unknown. Evidence suggests that the inflammatory-mediated disease model, such as that found with periodontal disease due to Porphyromonas gingivalis (P. gingivalis ), plays a role in AD progression. Objective: This study aims to systematically review the literature on the association between P. gingivalis to AD, and to identify the homogeneity of the methods used across studies to measure P. gingivalis …involvement in AD. Methods: We systematically searched studies on Cochrane library, Ovid Medline, PubMed, Web of Science, WHOLIS, Google Scholar databases, and reference lists of identified studies. Results: 6 studies out of 636 identified records fulfilled all eligibility criteria. Results showed no clear pathophysiology of AD due to P. gingivalis and its various virulence factors. No consensus was found in the literature pertaining to the method of measurement of AD or P. gingivalis and its virulence factors. Conclusion: The included studies suggest that P. gingivalis bacteria play a role in the process of systemic inflammation which leads to cerebrospinal fluid inflammation and indirectly cause hastening of AD onset and progression. Our included studies revealed heterogeneity in the methodologies of measurement of AD and/or P. gingivalis and its virulence factors, which opens discussion about the benefits and weakness of possible standardization. Show more

Keywords: Alzheimer’s disease, dementia, geriatrics, P. gingivalis , periodontitis, systematic review

DOI: 10.3233/ADR-200237

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 721-732, 2021

Authors: Paley, Elena L.

Article Type: Research Article

Abstract: The author discussed recently the possible molecular mechanisms that cause the COVID-19 disease symptoms. Here the analysis of the recent experimental data supports the hypothesis that production of the gut microbial tryptamine can be induced by the SARS-CoV-2 fecal viral activity due to the selective pressure or positive selection of tryptamine-producing microorganisms. In this report, the author suggests that the mechanism of microbial selection bases on the abilities of tryptamine to affect the viral nucleic acid. In other words, the gut microorganisms producing tryptamine are more resistant to SARS-CoV-2 fecal viral activity than microorganisms producing no tryptamine. Earlier we demonstrated …the induction of neurodegeneration by tryptamine in human cells and mouse brain. Furthermore, we were able to uncover the human gut bacteria associated with Alzheimer’s disease (AD) using PCR testing of human fecal samples with the new-designed primers targeting the tryptophan-tryptamine pathway. Likely, SARS-CoV-2 is one of the selective pressure factors in the cascade accelerating the neurodegenerative process in AD. This suggestion is consistent with a higher proportion of AD patients among COVID-19 related victims. Gut microbial tryptamine increase due to the viral infection-induced dysbiosis can synergize and potentiate the tryptamine cytotoxicity, necrotizing ability and other properties as a virulence factor. Show more

Keywords: Alzheimer’s disease, COVID-19, dysbiosis, human gut microbiome biogenic amines, necrotizing ability, PCR testing, SARS-CoV-2, tryptamine-induced model of neurodegeneration, tryptophanyl-tRNA synthetase

DOI: 10.3233/ADR-210032

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 733-738, 2021

Authors: O’Caoimh, Rónán | Calnan, Mareeta | Dhar, Arup | Molloy, D. William

Article Type: Research Article

Abstract: Background: Although caregiver burden is common among carers of people with dementia, little is known about its prevalence and predictors among caregivers of patients attending memory clinics. Objective: To examine carer and patient-specific characteristics associated with caregiver burden across the cognitive spectrum in a memory clinic population. Methods: Consecutive patients referred to a university hospital geriatric memory clinic were included. Caregiver burden was scored using the Caregiver Burden Score (CBS), (modified Zarit), with scores≥15/30 suggesting burden. BPSD were measured with the dysfunctional behaviour rating instrument (DBRI). Cognition was screened using the Montreal Cognitive Assessment (MoCA) and …Quick Mild Cognitive Impairment (Qmci ) screen. Results: In all, 351 patients were included, median age 77 (±11) years; 65.5% were female. The prevalence of caregiver burden was 33.6% overall, increasing from 10.8% in subjective cognitive decline (SCD), to 15% in mild cognitive impairment (MCI) and 43% in dementia; CBS scores were significantly higher in dementia (p  < 0.001). Caregivers with burden were significantly younger (p  = 0.045) and were more likely to be adult children (p  = 0.007). The CBS weakly correlated with the stage of cognitive impairment (r  = 0.16) but had moderate correlation with MoCA (r  = –0.54) and Qmci scores (r  = –0.60). After adjustment for co-variates, DBRI scores alone independently predicted burden (odds ratio 1.23;1.11–1.35, p  < 0.001). Conclusion: Caregiver burden is associated with the stage of cognitive impairment, with higher prevalence proportions in those with dementia compared with MCI and SCD. Only the severity of neuropsychiatric symptoms independently predicted caregiver burden in this population and its presence should prompt assessment for burden. Show more

Keywords: Caregiver burden, carers, dementia, memory clinic, mild cognitive impairment, predictors, prevalence

DOI: 10.3233/ADR-201003

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 739-747, 2021

Authors: Habiba, Umma | Ozawa, Makiko | Chambers, James K. | Uchida, Kazuyuki | Descallar, Joseph | Nakayama, Hiroyuki | Summers, Brian A. | Morley, John W. | Tayebi, Mourad

Article Type: Research Article

Abstract: Background: Canine cognitive dysfunction (CCD) is a progressive syndrome recognized in mature to aged dogs with a variety of neuropathological changes similar to human Alzheimer’s disease (AD), for which it is thought to be a good natural model. However, the presence of hyperphosphorylated tau protein (p-Tau) in dogs with CCD has only been demonstrated infrequently. Objective: The aim of the present study was to investigate the presence of p-Tau and amyloid-β oligomer (Aβo) in cerebral cortex and hippocampus of dogs with CCD, with focus on an epitope retrieval protocol to unmask p-Tau. Methods: Immunohistochemical and immunofluorescence …analysis of the cortical and hippocampal regions of five CCD-affected and two nondemented aged dogs using 4G8 anti-Aβp, anti-Aβ1 - 42 nanobody (PrioAD13) and AT8 anti-p-Tau (Ser202, Thr205) antibody were used to demonstrate the presence of Aβ plaques (Aβp) and Aβ1 - 42 oligomers and p-Tau deposits, respectively. Results: The extracellular Aβ senile plaques were of the diffuse type which lack the dense core normally seen in human AD. While p-Tau deposits displayed a widespread pattern and closely resembled the typical human neuropathology, they did not co-localize with the Aβp. Of considerable interest, however, widespread intraneuronal deposition of Aβ1 - 42 oligomers were exhibited in the frontal cortex and hippocampal region that co-localized with p-Tau. Conclusion: Taken together, these findings reveal further shared neuropathologic features of AD and CCD, supporting the case that aged dogs afflicted with CCD offer a relevant model for investigating human AD. Show more

Keywords: Alzheimer’s disease, Aβ1 - 42 oligomers, amyloid-β plaques, canine cognitive dysfunction, hyperphosphorylated tau

DOI: 10.3233/ADR-210035

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 749-760, 2021

Authors: Hu, Chaur-Jong | Chiu, Ming-Jang | Pai, Ming-Chyi | Yan, Sui-Hing | Wang, Pei-Ning | Chiu, Pai-Yi | Lin, Chin-Hsien | Chen, Ta-Fu | Yang, Fu-Chi | Huang, Kuo-Lun | Hsu, Yi-Ting | Hou, Yi-Chou | Lin, Wei-Che | Lu, Cheng-Hsien | Huang, Li-Kai | Yang, Shieh-Yueh

Article Type: Research Article

Abstract: Background: In Alzheimer’s disease (AD), cognitive impairment begins 10–15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-β 1-42×total tau protein higher than 455 pg2 /ml2 are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD). Objective: The prevalence of high-risk for dementia in cognitively normal controls is explored by assaying plasma biomarkers. Methods: 422 subjects with normal cognition were enrolled around Taiwan. …Plasma Aβ1-40 , Aβ1-42 , and T-Tau levels were assayed using immunomagnetic reduction to assess the risk of dementia. Results: The results showed that 4.6% of young adults (age: 20–44 years), 8.5% of middle-aged adults (age: 45–64 years), and 7.3% of elderly adults (age: 65–90 years) had HRAD. The percentage of individuals with HRAD dramatically increased in middle-aged and elderly adults compared to young adults. Conclusion: The percentage of HRAD in cognitively normal subjects are approximately 10%, which reveals that the potentially public-health problem of AD in normal population. Although the subject having abnormal levels of Aβ or tau is not definitely going on to develop cognitive declines or AD, the risk of suffering cognitive impairment in future is relatively high. Suitable managements are suggested for these high-risk cognitively normal population. Worth noting, attention should be paid to preventing cognitive impairment due to AD, not only in elderly adults but also middle-aged adults. Show more

Keywords: Alzheimer’s disease, immunomagnetic reduction, normal cognition, plasma biomarkers

DOI: 10.3233/ADR-210310

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 761-770, 2021