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

Authors: Jackson, Jordan M. | Bay, Allison A. | Barter, Jolie Denise | Ni, Liang | Caudle, William Michael | Serra, Monica C. | Wharton, Whitney | Hackney, Madeleine E.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a prevalent neurodegenerative disease. Treatments are necessary to target people at high risk for AD. Inflammation, particularly tumor necrosis factor alpha (TNFα ), appears to be an important marker associated with the development of AD pathophysiology. Consuming a high-fat diet induces tissue expression of TNFα . Objective: This study investigates the relationship between nutrition, circulating inflammation, and cognition in African American women (age: M  = 59.5 (±8.20) [42–73] years) at risk for developing AD. Methods: Participants were split into high-fat and low-fat groups based on total dietary fat consumption self-reported on the …Lower Mississippi Delta Nutrition Intervention Research Initiative Food Frequency Questionnaire (Delta NIRI FFQ). Results: A high-fat diet was associated with increased blood serum TNFα (p  = 0.02) compared to the low-fat diet. In addition, global cognition scores were 9.0% better in those who consumed a higher fat diet (p  = 0.04). No significant differences across groups were noted for executive function, dual-tasking, and visuospatial performance. Conclusion: These results indicate that there may be multiple biological pathways involved in AD development, suggesting the need for more holistic approaches to mitigate AD-development risk. Show more

Keywords: African American, Alzheimer’s disease, cognition, executive function, inflammation, nutrition, tumor necrosis alpha

DOI: 10.3233/ADR-200224

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 345-352, 2020

Authors: Moura, Eric L.R. | dos Santos, Hellin | Celes, Ana Paula M. | Bassani, Taysa B. | Souza, Leonardo C. | Vital, Maria A.B.F.

Article Type: Research Article

Abstract: Background: It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways. Objective: The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals. Methods: The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with …AZ1 formulation (Instanth® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n  = 6–10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was evaluated at day 28 using the object recognition test and the spatial version of the Y-maze test. At day 30, the rats were anesthetized with chloral hydrate (400 mg/kg, i.p) and euthanized in order to evaluate IBA1 in the hippocampus. The differences were analyzed using one-way ANOVA with Bonferroni’s or Kruskal Wallis with Dunn’s post-hoc test. Results/Conclusion: STZ-lesioned rats present memory impairment besides the increased microglial activation. The treatment with AZ1 formulation reversed the memory impairment observed in the object recognition test and Y-maze and also reduced IBA1 in CA1 and DG. Show more

Keywords: Alzheimer’s disease, IBA1, Instanth® NEO, object recognition test, streptozotocin, Y maze

DOI: 10.3233/ADR-200175

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 353-363, 2020

Authors: Young, John K.

Article Type: Research Article

Abstract: One unexplained feature of Alzheimer’s disease (AD) is that the lateral entorhinal cortex undergoes neurodegeneration before other brain areas. However, this brain region does not have elevated levels of amyloid peptides in comparison with undamaged regions. What is the cause of this special vulnerability of the entorhinal cortex? One special feature of the lateral entorhinal cortex is that it projects to newborn neurons that have undergone adult neurogenesis in the dentate gyrus of the hippocampus. Neurogenesis is abnormal in human AD brains, and modulation of neurogenesis in experimental animals influences the course of AD. This complex process of neurogenesis may …expose axon terminals originating from neurons of the entorhinal cortex to a unique combination of molecules that can enhance toxic effects of amyloid. Retrograde degeneration of neurons with axons terminating in the dentate gyrus provides a likely explanation for the spatial patterns of neuronal cell death seen in AD. Specialized astrocytes in the dentate gyrus participate in adult neurogenesis and produce fatty acid binding protein7 (FABP7). These FABP7+ cells undergo an aging-related mitochondrial pathology that likely impairs their functions. This age-related abnormality may contribute to the impairment in neurogenesis seen in aging and Alzheimer’s disease. Also, a compromised function of these astrocytes likely results in local elevations of palmitic acid, iron, copper, and glucose, which all enhance the toxicity of amyloid peptides. Treatments that modulate neurogenesis or diminish the production of these toxic substances may prove more successful than treatments that are solely aimed at reducing the amyloid burden alone. Show more

Keywords: Alzheimer’s disease, astrocytes, copper, entorhinal cortex, FABP7, Gomori-positive, neurogenesis

DOI: 10.3233/ADR-200218

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 365-371, 2020

Authors: Lehrer, Steven | Rheinstein, Peter H.

Article Type: Research Article

Abstract: Background: The cause of Alzheimer’s disease (AD) is poorly understood. Neurotropic microbes, particularly herpesviruses, might set off chronic neuroinflammation. Amyloid-β (Aβ) has antimicrobial properties and could represent a brain defense against infection. Objective: We searched for protein sequence alignment between herpes simplex virus type I (HSV-1) HSV-2, and Aβ. Methods: Protein data bank (pdb) structures for Aβ, HSV-1, and HSV-2 were searched on the RCSB Protein Data Bank. The protein structures were superimposed and aligned on PYMOL v 2.3.4. Results: For HSV-1 and Aβ, amino acid residues ser549 – his569 of HSV-1 aligned closely …with residues asp7 - asn27 of Aβ. For HSV-2 and Aβ, amino acid residues of HSV-2 aligned less closely than those of HSV-1 with residues of Aβ. Conclusion: Conjugating and binding to the same alpha helix in the HSV-1 protease, Aβ could be marking HSV-1 for attack by the immune system, providing a rapid inherited immune response to a destructive neurotropic virus that would otherwise require the more time-consuming involvement of T-cells, B-cells, and the adaptive immune system. But older people do not respond to viral infections as well as younger individuals. When HSV-1 infection advances in an old person, more and more amyloid is produced, forming an adhesive web. As the brain tries to hold the pathologic process in check, neuroinflammation increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome. Show more

Keywords: Alignment, Alzheimer’s disease, amyloid-β, protein, virus

DOI: 10.3233/ADR-200231

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 373-377, 2020

Authors: Andreev, Alexander | Erdinc, Burak | Shivaraj, Kiran | Schmutz, Julia | Levochkina, Olga | Bhowmik, Dhrity | Farag, Fady | Money, Kelli M. | Primavera, Louis H. | Gotlieb, Vladimir | Sahni, Sonu

Article Type: Research Article

Abstract: Background: Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer’s disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively. Objective: To study an association between ADRD and anemia of chronic inflammation. Methods: We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were …performed using a Mann–Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population. Results: There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p -value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p  < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p  < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p  < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2–8.4] and 13% [95% CI: 9.8–16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8–22.1]. Conclusion: We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease and related dementia, anemia, anemia of chronic inflammation, dementia

DOI: 10.3233/ADR-200178

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 379-391, 2020

Authors: Kudoh, Chiaki | Hori, Tomokatsu | Yasaki, Shunji | Ubagai, Ryu | Tabira, Takeshi

Article Type: Short Communication

Abstract: We conducted a multicenter, randomized, double-blind, placebo-controlled prospective trial examining a supplement containing ferulic acid and Angelica archangelica extract (Feru-guard ® ) for mild cognitive impairment (MCI). In the intention-to-treat population, Mini-Mental State Examination (MMSE) scores were significantly better at 24 weeks (p  = 0.041) in the active group. In the per protocol population, MMSE was significantly better in the active group at 24 weeks (p  = 0.008), and mixed effect models for repeated measures (MMRM) showed significant difference (p  = 0.016). ADAS-Jcog was significantly better at 24 (p  = 0.035) and 48 weeks (p  = 0.015) in the active group, and MMRM was significant …(p  = 0.031). Thus, Feru-guard ® may be useful for MCI. Show more

Keywords: Angelica archangelica, dementia, dietary supplement, double-blind randomized trial, ferulic acid, mild cognitive impairment

DOI: 10.3233/ADR-200211

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 393-398, 2020

Authors: Ben Zaken, Sara | Radomysky, Zorian | Koren, Gideon

Article Type: Research Article

Abstract: Background: High magnesium intake has been associated with a decreased risk of dementia. In contrast, other research has found that both low and high serum magnesium levels were associated with an increased risk of Alzheimer’s disease and mixed dementia. Hence, presently the role of magnesium levels in dementia is unclear. Objective: To investigate a possible association between serum magnesium concentrations and dementia in a large population-based sample. Methods: Maccabi Healthcare Service in Israel provides healthcare to over 2 million citizens. Maccabi maintains a registry with approximately 26,000 diagnosed dementia patients. We focused on patients of both …sexes with Alzheimer’s disease or mixed dementia aged 65 or older, excluding patients with clinical diagnoses that could affect serum magnesium level, or with other causes of cognitive decline. Our control group consisted of patients of the same age and sex without dementia. Results: No significant differences were found in mean, mode, and median magnesium levels between the dementia and control groups. However, there were marginally but significantly more cases with low magnesium levels among dementia patients than among controls: A total of 9.4% of tests done in patients with dementia and 7.81% done in non-dementia subjects were hypomagnesemic (p  <  0.00001). Conclusion: Despite similar means and medians of serum magnesium in dementia and controls, the proportion of lower than normal magnesium test results was slightly higher among dementia patients. It is possible that patients with dementia have more episodes of hypomagnesemia than controls, despite similar overall mean levels of magnesium. Show more

Keywords: Alzheimer’s disease, magnesium, mixed dementia, serum magnesium

DOI: 10.3233/ADR-200220

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 399-404, 2020

Authors: Trindade, Paula Gasparini Emery | Santos, Raquel Luiza | Johannessen, Aud | Neto, Jose Pedro Simões | Dourado, Marcia Cristina Nascimento

Article Type: Research Article

Abstract: Background: Awareness of functional status may underlie specific profiles and differences related to stage severity in individuals with Alzheimer’s disease (AD). Objective: This study aimed to assess self-reported experiences of awareness of functional activity in people with mild and moderate AD. Methods: This is a mixed methods approach. The qualitative part was conducted through semi-structured interviews concerning the experiences and awareness of deficits in 38 older adults with mild or moderate AD. The quantitative approach included a comparison between groups with regard to concerns of awareness and clinic and demographic data. Results: Impairment on …awareness of disease and awareness of functional deficits was observed even in the mild stages of AD. There was also a noticeable progression of impairments of both kinds of awareness from mild to moderate stage of disease. The majority of participants with mild and moderate AD were partially aware of their functional deficits. Both groups of participants reported some negative impact; however, they were not able to entirely describe their functional status. Also, deficits to recognize the need for help with hygiene and general tasks were observed. Significant differences were found in awareness of need for help with general tasks and awareness of need for help with hygiene tasks. Conclusion: People with mild and moderate AD may describe their aware of the disease better than specific functional deficits, and most of them can provide some reports concerning to the impact of the disease. Show more

Keywords: Activities of daily living, awareness, cognition, dementia, disease

DOI: 10.3233/ADR-200227

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 405-415, 2020

Authors: Pradeep, Sushma | Jain, Anisha S. | Dharmashekara, Chandan | Prasad, Shashanka K. | Kollur, Shiva Prasad | Syed, Asad | Shivamallu, Chandan

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) was first described in 1907 and got its name after Alois Alzheimer, a German psychiatrist and neuropathologist. This disease starts slow, increasing gradually to worsen in the due course of time. AD is mainly characterized by the associated dementia, which is a decline of cognitive effects such as memory, praxis, and orientation. The dementia is further highlighted by the presence of psychological and behavioral symptoms. Additionally, AD is also associated with the multiple interconnected pathways linked neuropathological changes such as the formation of neurofibrillary tangles and amyloid-β plaques inside the brain. AD therapeutics have been of prime …concern over the decades, resulting in the elucidation of promising therapeutic targets. The requirement of AD stage dependent optimized conditions has necessitated a combinatorial approach toward treatment. The priority in AD research has remained to develop disease-modifying and development-reducing drugs for treatment regimens followed during the early and later stages, respectively. Show more

Keywords: Dementia, neuropathologist, plaques, psychiatrist, tangles

DOI: 10.3233/ADR-200228

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 417-429, 2020

Authors: Franco-Macías, Emilio | Rodrigo-Herrero, Silvia | Luque-Tirado, Andrea | Méndez-Barrio, Carlota | Medina-Rodriguez, Manuel | Graciani-Cantisán, Eugenia | Sánchez-Arjona, María Bernal | Maillet, Didier

Article Type: Research Article

Abstract: Background: Memory tests focused on binding may be more sensitive to diagnose Alzheimer’s disease (AD) at an early phase. TMA-93 examines relational binding by images. Objective: Evaluate the reliability (internal consistency and inter-rater and test-retest reliability) and feasibility of the TMA-93 in a clinic setting with low-educated individuals and limited face-to-face time per patient. Methods: The study was undertaken in a neurology outpatient clinic of a hospital in Southern Spain. The internal consistency of the TMA-93 was estimated in 35 patients with amnestic mild cognitive impairment (aMCI) and 40 healthy controls (HCs). The inter-rater reliability (by …two raters) and feasibility (by recording the percentage of participants who completed the test, and by timing the administration time) were evaluated in HCs (n  = 16), aMCI patients (n  = 18), and mild dementia patients (n  = 15). The test-retest reliability for the TMA-93 total score was studied in 51 HCs tested by the same examiner 2–4 months apart. The internal consistency was estimated by Cronbach’s alpha. The inter-rater and test-retest reliability was quantified by the intraclass correlation coefficient (ICC). The administration time was compared by diagnosis. Results: The internal consistency was “optimal” (Cronbach’s alpha = 0.936). The test-retest reliability was “good” [ICC = 0.802 (CI 95%  = 0.653–0.887)]. The inter-rater reliability was “optimal” [ICC = 0.999, (CI 95%  = 0.999–1)]. All participants completed the test. The administration time ranged from less than 3 min in HCs to 6 min in aMCI patients, and 7 min in mild dementia patients. Conclusion: Good feasibility and reliability support using the TMA-93 for examining visual relational binding, particularly in the context of low-educational attainment and limited time per patient. Show more

Keywords: Binding, feasibility, inter-rater reliability, internal consistency, mild cognitive impairment, test-retest reliability, TMA-93

DOI: 10.3233/ADR-200215

Citation: Journal of Alzheimer's Disease Reports, vol. 4, no. 1, pp. 431-440, 2020