Journal of Alzheimer's Disease Reports - Volume 4, issue 1

Authors: Nakanishi, Miharu | Niimura, Junko | Ziylan, Canan | Bakker, Ton TJEM | Granvik, Eva | Nägga, Katarina | Shindo, Yumi | Nishida, Atsushi

Article Type: Research Article

Abstract: Background: There are no studies on how the same psychosocial dementia care program is adapted to both in-home and residential care settings. Objective: To evaluate the time investment required by professionals to implement a psychosocial dementia care program to manage neuropsychiatric symptoms. Methods: A prospective observational study design was used. The program consisted of 1) a one-day training course, 2) three interdisciplinary discussion meetings in five months, and 3) a web-based tool for the continued assessment of neuropsychiatric symptoms. Care professionals implemented the intervention in in-home (19 in-home care management agencies and 14 multiple in-home service …providers) and residential care settings (19 group homes and eight nursing homes) in Japan from October 2019 to February 2020. The level of neuropsychiatric symptoms for the participants was evaluated using the Neuropsychiatric Inventory (NPI: 0–144). The time investment was reported by participating professionals. A total of 125 persons with dementia were included at baseline. Results: Neuropsychiatric symptoms were significantly decreased at the final follow-up in all types of providers (Cohen’s drm  = 0.44–0.61). The mean (SD) time required for the five-month implementation was 417.9 (219.8) minutes. There was a mean (SD) decrease of 8.6 (14.0) points in the total NPI score among the 103 persons with completed interventions. The time investment was significantly lower in in-home care management agencies than in group homes, and lower in follow-ups than at baseline assessment. Conclusion: The program implementation may incur a substantial time investment regardless of setting. An additional benefit scheme to reward the time investment would be helpful to encourage implementation until the follow-ups. Show more

Keywords: Behavioral symptoms, dementia, group homes, home care agencies, nursing homes, psychosocial support systems

DOI: 10.3233/ADR-200235

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 441-453, 2020

Authors: El Haj, Mohamad | Larøi, Frank | Gallouj, Karim

Article Type: Short Communication

Abstract: While social distancing may be deemed necessary in order to avoid COVID-19 infections, the lockdown may impact mental health of patients with Alzheimer’s disease (AD). We present a case study involving hallucinations in a patient with AD who lives in a nursing home during the COVID-19 crisis. We compared this patient’s hallucination scores before and during the lockdown. We observed increased hallucinations during, compared to before, the lockdown. These increased hallucinations can be attributed to a number of elements such as the decreased in daily activities, social distancing, lack of physical contact with family members, and loneliness during the lockdown.

Keywords: Alzheimer’s disease, COVID-19, hallucinations, social distancing

DOI: 10.3233/ADR-200241

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 455-458, 2020

Authors: Wu, Zimu | Phyo, Aung Zaw Zaw | Al-harbi, Tagrid | Woods, Robyn L. | Ryan, Joanne

Article Type: Review Article

Abstract: Background: Cognitive aging is a dynamic process in late life with significant heterogeneity across individuals. Objective: To review the evidence for latent classes of cognitive trajectories and to identify the associated predictors and outcomes. Methods: A systematic search was performed in MEDLINE and EMBASE for articles that identified two or more cognitive trajectories in adults. The study was conducted following the PRISMA statement. Results: Thirty-seven studies were included, ranging from 219 to 9,704 participants, with a mean age of 60 to 93.4 years. Most studies (n  = 30) identified distinct cognitive trajectories using latent class …growth analysis. The trajectory profile commonly consisted of three to four classes with progressively decreasing baseline and increasing rate of decline—a ‘stable-high’ class characterized as maintenance of cognitive function at high level, a ‘minor-decline’ class or ‘stable-medium’ class that declines gradually over time, and a ‘rapid-decline’ class with the steepest downward slope. Generally, membership of better classes was predicted by younger age, being female, more years of education, better health, healthier lifestyle, higher social engagement and lack of genetic risk variants. Some factors (e.g., education) were found to be associated with cognitive function over time only within individual classes. Conclusion: Cognitive aging in late life is a dynamic process with significant inter-individual variability. However, it remains unclear whether similar patterns of cognitive aging are observed across all cognitive domains. Further research into unique factors which promote the maintenance of high-cognitive function is needed to help inform public policy. Show more

Keywords: Cognitive function, longitudinal, older adults, prospective, risk factors, trajectory

DOI: 10.3233/ADR-200232

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 459-478, 2020

Authors: Robbins, James | Busquets, Oriol | Tong, Ming | de la Monte, Suzanne M.

Article Type: Research Article

Abstract: Background: Brain insulin resistance and deficiency are well-recognized abnormalities in Alzheimer’s disease (AD) and likely mediators of impaired energy metabolism. Since apolipoprotein E (APOE ) is a major risk factor for late-onset AD, it was of interest to examine its potential contribution to altered insulin-linked signaling networks in the brain. Objective: The main goal was to evaluate the independent and interactive contributions of AD severity and APOE ɛ 4 dose on brain expression of insulin-related polypeptides and inflammatory mediators of metabolic dysfunction. Methods: Postmortem fresh frozen frontal lobe tissue from banked cases with known APOE …genotypes and different AD Braak stages were used to measure insulin network polypeptide immunoreactivity with a commercial multiplex enzyme-linked immunosorbent assay (ELISA). Results: Significant AD Braak stage and APOE genotype-related abnormalities in insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucaton-like peptide-1 (GLP-1), leptin, ghrelin, glucagon, resistin, and plasminogen activator inhibitor-1 (PAI-1) were detected. The main factors inhibiting polypeptide expression and promoting neuro-inflammatory responses included AD Braak stage and APOE ɛ 4/ɛ 4 rather than ɛ 3/ɛ 4. Conclusion: This study demonstrates an expanded role for impaired expression of insulin-related network polypeptides as well as neuroinflammatory mediators of brain insulin resistance in AD pathogenesis and progression. In addition, the findings show that APOE has independent and additive effects on these aberrations in brain polypeptide expression, but the impact is decidedly greater for APOE ɛ 4/ɛ 4 than ɛ 3/ɛ 4. Show more

Keywords: Alzheimer’s disease, APOE, Braak stage, human brain, incretins, insulin resistance, leptin, multiplex ELISA, neurodegeneration, neuroinflammation

DOI: 10.3233/ADR-200238

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 479-493, 2020

Authors: Klawitter, Lukus | Mahoney, Sean J. | Dahl, Lindsey | Hackney, Kyle J. | Herrmann, Stephen D. | Edwards, Bradley | McGrath, Ryan

Article Type: Short Communication

Abstract: Handgrip dynamometers are used to assess handgrip strength (HGS), and low HGS is linked to poor cognitive function. Although HGS is a reliable measure of muscle function, it is only measuring maximal grip force. Other aspects of muscle function such as force control, fatigability, and steadiness are unaccounted for in current HGS protocols. This pilot study sought to determine the role of maximal HGS, submaximal HGS force control, HGS fatigability, and HGS neuromuscular steadiness on cognitive function in older adults. Our findings indicate that these additional HGS measurements could factor into detecting poorer cognitive functioning, while also evolving HGS protocols.

Keywords: Aging, geriatrics, geriatric assessment, mental status and dementia tests, muscle strength, muscle weakness, nervous system diseases

DOI: 10.3233/ADR-200225

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 495-499, 2020

Authors: Kanagasingam, Shalini | Chukkapalli, Sasanka S. | Welbury, Richard | Singhrao, Sim K.

Article Type: Review Article

Abstract: Porphyromonas gingivalis (P. gingivalis ) is one of the several important bacterial pathogens associated with the sporadic Alzheimer’s disease (AD). Different serotypes are either capsulated or are non-capsulated. It has been demonstrated that P. gingivalis (non-capsulated) can reproduce the neurodegenerative AD-like changes in vitro , and a capsular P. gingivalis (strain W83) could reproduce the cardinal hallmark lesions of AD in a wild-type mouse model. All P. gingivalis forms express proteolytically active proteases that enable cleavage of the amyloid-β protin precursor (AβPP) and tau resulting in the formation of amyloid-β and neurofibrillary tangles. Tau is an …established substrate for gingipains, which can cleave tau into various peptides. Some of the P. gingivalis fragmented tau protein peptides contain “VQIINK” and “VQIVYK” hexapeptide motifs which map to the flanking regions of the microtubule binding domains and are also found in paired helical filaments that form NFTs. P. gingivalis can induce peripheral inflammation in periodontitis and can also initiate signaling pathways that activate kinases, which in turn, phosphorylate neuronal tau. Periodontal disease related inflammation has metabolic implications for an individual’s peripheral and brain health as patients suffering from generalized periodontitis often have related co-morbidities and are “at risk” of developing AD. The aim here is to discuss the role of P. gingivalis behind such associations with the backdrop of huge efforts to test P. gingivalis virulence factors clinically (GAIN Trial: Phase 2/3 Study of COR388 in Subjects with AD) with inhibitors, which may lead to an intervention by reducing the pathogenic bacterial load. Show more

Keywords: Alzheimer’s disease, gingipains, periodontal disease, Porphyromonas gingivalis

DOI: 10.3233/ADR-200250

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 501-511, 2020

Authors: Garba, Asabe E. | Grossberg, George T. | Enard, Kimberly R. | Jano, Fabian J. | Roberts, Emma N. | Marx, Charlotte A. | Buchanan, Paula M.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the 6th leading cause of death in the United States and has no cure or progression prevention. The Cognitive Reserve (CR) theory poses that constant brain activity earlier in life later helps to deter pathological changes in the brain, delaying the onset of disease symptoms. Objective: To determine the reliability and validity of the Cognitive Reserve Index questionnaire (CRIq) in AD patients. Methods: Primary data collection was done using the CRIq to quantify CR in 90 participants. Correlations and multivariable linear regressions were used to assess reliability and validity. …Results: Reliability was tested in 34 participants. A Pearson correlation coefficient of 0.89 (p  < 0.001) indicated a strong positive correlation. Validity was tested in 33 participants. A Pearson correlation coefficient of 0.30 (p  = 0.10) indicated an insignificant weak positive correlation. Conclusion: The CRIq was found reliable. Gaining a better understanding of how CR tools can be used in various cognitive populations will help with the establishment of a research tool that is universally accepted as a true CR measure. Show more

Keywords: Alzheimer’s disease, cognitive reserve, reliability and validity, surveys and questionnaires, wechsler scales

DOI: 10.3233/ADR-200244

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 513-524, 2020

Authors: Madsen, Steven J. | DiGiacomo, Phillip S. | Zeng, Yitian | Goubran, Maged | Chen, Yuanxin | Rutt, Brian K. | Born, Donald | Vogel, Hannes | Sinclair, Robert | Zeineh, Michael M.

Article Type: Research Article

Abstract: Background: Recent evidence suggests that the accumulation of iron, specifically ferrous Fe2+ , may play a role in the development and progression of neurodegeneration in Alzheimer’s disease (AD) through the production of oxidative stress. Objective: To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology. Methods: We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of …specific iron-rich regions of interest. Results: Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit. Conclusion: These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aβ, tau, iron, and other putative metals, such as zinc. Show more

Keywords: Alzheimer’s disease, correlative microscopy, histopathology, iron, neuroinflammation, oxidative stress, specimen MRI

DOI: 10.3233/ADR-200234

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 525-536, 2020

Authors: Rangon, Claire-Marie | Krantic, Slavica | Moyse, Emmanuel | Fougère, Bertrand

Article Type: Review Article

Abstract: Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer’s disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem …autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory “storm”. The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19. Show more

Keywords: Brainstem, dysautonomia, heart rate variability, neuro-immune axis, pulmonary ventilation, vagus nerve, vagus nerve stimulation

DOI: 10.3233/ADR-200273

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 537-551, 2020