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

Authors: Innes, Kim E. | Montgomery, Caitlin | Selfe, Terry Kit | Wen, Sijin | Khalsa, Dharma Singh | Flick, Madison

Article Type: Research Article

Abstract: Background: Recent studies suggest meditation and music listening (ML) may improve cognitive and psychosocial outcomes in adults with subjective cognitive decline (SCD). However, lack of a usual care group has limited conclusions. Objective: To assess the: 1) feasibility of incorporating an enhanced usual care (EUC) comparator in a trial of Kirtan Kriya meditation (KK) and ML for adults experiencing SCD; and 2) preliminary effects of active treatment (KK/ML) versus an EUC program. Methods: Forty participants with SCD were randomized 1:1:2 to a 12-week KK, ML, or EUC program. KK and ML participants were asked to practice …12 minutes/day; EUC participants were given a comprehensive educational packet regarding healthy aging and strategies for improving/maintaining brain health and asked to record any activities or strategies used. Feasibility was assessed using measures of retention, adherence, treatment expectancies, and participant satisfaction, as well as information from exit questionnaires and daily practice/activity logs. Cognitive functioning, stress, mood, sleep-quality, and health-related quality of life (QOL) were measured pre- and post-intervention using well-validated instruments. Results: Thirty-two participants (80%) completed the 3-month study, with retention highest in the EUC group (p  < 0.05). Active treatment participants averaged 6.0±0.4 practice sessions/week, and EUC participants, 7.5±0.6 brain health activities/week. Treatment expectancies were similar across groups. EUC participants indicated high satisfaction with the program and study. Despite limited study power, the active treatment group showed significantly greater gains in subjective memory functioning (ps≤0.025) and nonsignificant improvements in cognitive performance (TMT-B), perceived stress, QOL, and mood (ps≤0.08) compared to the EUC group. Conclusion: Findings of this pilot feasibility trial suggest incorporation of an EUC program is feasible, and that participation in a simple 12-week relaxation program may be helpful for adults with SCD versus engagement in an EUC program. Show more

Keywords: Acceptability, Alzheimer’s disease, cognition, memory complaints, mind-body therapy, mood, quality of life, stress, subjective cognitive impairment

DOI: 10.3233/ADR-200249

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 187-206, 2021

Authors: Sabbagh, Marwan | Miller, Justin | Jones, Stephen | Ritter, Aaron | Shi, Jiong | DeCourt, Boris | Wint, Dylan

Article Type: Research Article

Abstract: Background: Informant-based measures are effective screening tools for cognitive impairment. The Alzheimer’s Questionnaire (AQ) is a subjective, informant-based measure that detects amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) with high sensitivity and specificity and has been shown to predict amyloid burden. Objective: To determine whether informant-based report of cognitive decline correlates with hippocampal volume changes in MCI and AD. Methods: Retrospective chart review of 139 clinically referred patients with clinical diagnoses of aMCI or mild dementia due to AD was conducted. Diagnostic status (clinical diagnosis made by a neurologist), NeuroQuant measured MRI brain with …percentile rank hippocampal volume, Montreal Cognitive Assessment (MoCA) total, AQ-Total score, and demographic variables were extracted from medical records. Spearman correlation was used to assess the relationship between hippocampal volume and AQ-Total. The AQ was used to assign diagnostic status. Thus, the relationship between the AQ and diagnostic status was excluded. Results: The sample include 88 female and 51 male participants. The mean age was 74.37±9.45, mean MOCA was 22.65±4.18, mean education was 14.80±3.35, and mean AQ score was 10.54±5.22. Hippocampal volume and the AQ correlation was r  = –0.33 [95%CI –0.47 to –0.17], p  < 0.0001. Conclusion: In a mixed-clinical sample of patients presenting to an outpatient memory disorders center, higher endorseme-nts of functional impairments by caregivers were significantly associated with smaller hippocampal volumes. When used in conjunction with other available measures, these findings further support the role of the AQ in clinical decision-making and demonstrate an additional relationship between clinical measures and volumetric MRI. Show more

Keywords: Alzheimer’s disease, Alzheimer’s Questionnaire, hippocampal volume, informant-based measures, screening tools

DOI: 10.3233/ADR-200260

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 207-211, 2021

Authors: Khan, Hafiz | Rafiq, Aamrin | Palle, Komaraiah | Faysel, Mohammad | Gabbidon, Kemesha | Chowdhury, Mohammed | Reddy, P. Hemachandra

Article Type: Research Article

Abstract: Background: The prevalence of cognitive dysfunction increases in elderly due to cardiovascular disease related risk factors in rural communities like West Texas. Objective: The purpose of this study was to find risk factors of cardiovascular disease (CVD) related to cognitive dysfunction and their impact on elderly adults in rural West Texans. Methods: Statistical methods such as Pearson’s chi-squared and a multinomial logistic regression were utilized to analyze data. We used SPSS software to detect and understand the nature of the risk factors. Results: A summary of statistics was obtained by using Pearson’s chi-squared test …for categorical variables. CVD, diabetes mellitus, and depression were significantly associated with cognitive dysfunction for both males and females (p  = 0.0001), whereas anxiety was found to be significantly associated with cognitive dysfunction for females (p  = 0.0001). Age group and race/ethnicity were significantly associated with cognitive dysfunction for both males and females (p  = 0.0001). By performing a multinomial logistic regression method and controlling for confounders, the significant risk factors (p  <  0.05)— age (65– 84 years), diabetes, and memory loss for age-associated cognitive impairment; diabetes for cognitive impairment no dementia; age (65– 84, ≥85 years), CVD, diabetes, depression, memory loss, non-Hispanic Whites, and Black/African-Americans for mild cognitive impairment; and age, memory loss, non-Hispanic Whites, Black/African-Americans, and male gender were found for dementia. Conclusion: CVD related risk factors in developing cognitive dysfunction exist and integrating such risk variables may guide relevant policy interventions to reduce Alzheimer’s incidence or dementia in rural communities in West Texans. Show more

Keywords: Alzheimer’s disease, cardiovascular disease, cognitive dysfunction FRONTIER database

DOI: 10.3233/ADR-200278

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 213-226, 2021

Authors: Gorantla, Nalini V. | Das, Rashmi | Mulani, Fayaj A. | Thulasiram, Hirekodathakallu V. | Chinnathambi, Subashchandrabose

Article Type: Correction

DOI: 10.3233/ADR-219001

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 227-227, 2021

Authors: Lopatko Lindman, Karin | Weidung, Bodil | Olsson, Jan | Josefsson, Maria | Johansson, Anders | Eriksson, Sture | Hallmans, Göran | Elgh, Fredrik | Lövheim, Hugo

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ), the key constituent of Alzheimer’s disease (AD) plaques, has antimicrobial properties. Objective: To investigate the association between plasma Aβ and antibodies against the AD-related pathogens herpes simplex virus (HSV), cytomegalovirus (CMV), and C. pneumoniae . Methods: Plasma from 339 AD cases, obtained on average 9.4 years (±4.00) before diagnosis, and their matched controls were analyzed for Aβ40 and Aβ42 concentrations with Luminex xMAP technology and INNOBIA plasma Aβ-form assays. Enzyme-linked immunosorbent assays were utilized for analyses of anti-HSV immunoglobulin (Ig) G, anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae …IgG. Follow-up samples were available for 150 of the cases. Results: Presence and levels of anti-HSV1 IgG, anti-HSV2 IgG, anti-CMV IgG, and anti-C. pneumoniae IgG did not correlate with concentrations of Aβ42 or Aβ40 in cases or controls. Conclusion: Levels of plasma Aβ were not associated with antibodies against different AD-related pathogens. Show more

Keywords: Alzheimer’s disease, amyloid-β peptides, Chlamydophila pneumoniae, cytomegalovirus, dementia, Herpes simplex, nested case-control study

DOI: 10.3233/ADR-210008

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 229-235, 2021

Authors: Olsen, Ingar

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) has been associated with periodontitis, which starts as gingivitis. Similar to periodontitis, gingivitis bacteria, bacterial products, and inflammatory mediators can travel to the brain via the blood stream and promote brain inflammation. Periodontal pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, both associated with AD, have been found in dental plaque of children already at the age of 3. It is suggested that these bacteria during long-term exposure may drive microglia (brain resident macrophage cells) into a pro-inflammatory M1 phase where they contribute to AD rather than protect against it. This notion comes from studies …in mice showing that microglia actually can “remember” previous inflammatory challenge and become “trained” or “tolerant” to toxins like lipopolysaccharide. If gingivitis has an impact on AD, which should be verified, AD prophylaxis should start already at this pre-periodontitis stage with removal of supragingival plaque. Show more

Keywords: Bacteria, bacteremia, inflammation, microglia, periodontitis, systemic

DOI: 10.3233/ADR-210006

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 237-241, 2021

Authors: Tombini, Mario | Assenza, Giovanni | Ricci, Lorenzo | Lanzone, Jacopo | Boscarino, Marilisa | Vico, Carlo | Magliozzi, Alessandro | Di Lazzaro, Vincenzo

Article Type: Review Article

Abstract: Increasing evidence coming from both experimental and humans’ studies strongly suggest the existence of a link between epilepsy, in particular temporal lobe epilepsy (TLE), and Alzheimer’s disease (AD). Patients with mild cognitive impairment and AD are more prone to have seizures, and seizures seem to facilitate amyloid-β and tau deposits, thus promoting neurodegenerative processes. Consistent with this view, long-lasting drug-resistant TLE and AD have been shown to share several pathological and neuroimaging features. Even if studies addressing prevalence of interictal and subclinical epileptiform activity in these patients are not yet conclusive, their findings raise the possibility that epileptiform activity might …negatively impact memory and hasten cognitive decline, either directly or by association with unrecognized silent seizures. In addition, data about detrimental effect of network hyperexcitability in temporal regions in the premorbid and early stages ofADopen up newtherapeutic opportunities for antiseizure medications and/or antiepileptic strategies that might complement or enhance existing therapies, and potentially modify disease progression. Here we provide a review of evidence linking epileptiform activity, network hyperexcitability, and AD, and their role promoting and accelerating neurodegenerative process. Finally, the effects of antiseizure medications on cognition and their optimal administration in patients with AD are summarized. Show more

Keywords: Alzheimer’s disease, antiseizure medications, cognition, epilepsy, epileptiform activity, network hyperexcitability

DOI: 10.3233/ADR-200286

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 243-261, 2021

Authors: Pahrudin Arrozi, Aslina | Yanagisawa, Daijiro | Kato, Tomoko | Akatsu, Hiroyasu | Hashizume, Yoshio | Kaneda, Daita | Tooyama, Ikuo

Article Type: Research Article

Abstract: Background: Emerging evidence indicates that the misfolded tau protein can propagate aggregates between cells in a prion-like manner. This prion activity has been typically studied in brain extracts of patients with Alzheimer’s disease (AD), but not in the olfactory region that can be a potential biomarker in AD. Objective: To investigate the prion seeding activity of tau in nasal mucosa tissues using a cell culture model of tau propagation. Methods: Brain and nasal mucosa homogenates were added to HEK293T cells expressing three repeat or four-repeat domains of tau with the L266V, V337M (3RD* VM) and P301L …and V377M mutations (4RD* LM) fused to the enhanced green fluorescence protein (EGFP) respectively. We also measured the level of phosphorylated tau (p-tau), total tau (t-tau), and p-tau/t-tau ratio and performed correlation analysis between tau prion activity and the level of tau. Results: We found that brain and nasal tissue homogenates from patients with AD significantly induced tau aggregation in HEK293T cells either expressing tau 3RD* VM-EGFP or 4RD* LM-EGFP compared with control brain and nasal tissue homogenates. The levels of p-tau and p-tau/t-tau ratio were significantly increased in the brain of patients with AD; however, no significant difference was found in nasal tissue compared with their respective control tissue homogenates. Conclusion: These results suggest that the nasal tissues contain tau seeds, similar to the brain, albeit without changes in the levels of p-tau and t-tau. Therefore, a cellular bioassay using nasal tissues would have great potential as an AD biomarker because of the usefulness of nasal tissue biopsy. Show more

Keywords: Alzheimer’s disease, nasal extracts, tau aggregation, tau propagation

DOI: 10.3233/ADR-210298

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 263-274, 2021

Authors: Bezuch, Natalia | Bradburn, Steven | Robinson, Andrew C. | Pendleton, Neil | Payton, Antony | Murgatroyd, Chris

Article Type: Research Article

Abstract: Background: The APOE ɛ4 allele is the strongest known genetic risk factor for sporadic Alzheimer’s disease (AD). The neighboring TOMM40 gene has also been implicated in AD due to its close proximity to APOE . Objective: Here we tested whether methylation of the TOMM40-APOE locus may influence ApoE protein levels and AD pathology. Methods: DNA methylation levels across the TOMM40-APOE locus and ApoE levels were measured in superior frontal gyrus tissues of 62 human brains genotyped for APOE and scored for AD neuropathology. Results: Methylation levels within the TOMM40 …CpG island in the promoter or APOE CpG island in Exon 4 did not differ between APOE ɛ4 carriers versus non-carriers. However, APOE ɛ4 carriers had significantly higher methylation the APOE promoter compared with non-carriers. Although DNA methylation at TOMM40 , APOE promoter region, or APOE did not differ between AD pathological groups, there was a negative association between TOMM40 methylation and CERAD scores. ApoE protein concentrations did not significantly different between APOE ɛ4 carriers and non-carriers, or between AD pathological groups. Finally, there was no correlation between ApoE protein concentrations and DNA methylation levels. Conclusion: APOE gene methylation may not be affected by genotype, relate to AD pathology or ApoE protein levels in the superior frontal gyrus, though, DNA methylation at the ApoE promoter differed between genotype. DNA methylation at TOMM40 associated with amyloid-β plaques and longitudinal fluid intelligence. In sum, these results suggest a complicated regulation of the TOMM40-APOE locus in the brain in controlling ApoE protein levels and AD neuropathology. Show more

Keywords: Alzheimer’s disease, APOE, DNA methylation, frontal gyrus, neuropathology, TOMM40

DOI: 10.3233/ADR-201000

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 275-282, 2021

Authors: Mold, Matthew John | O’Farrell, Adam | Morris, Benjamin | Exley, Christopher

Article Type: Research Article

Abstract: Background: Familial Alzheimer’s disease (fAD) is driven by genetic predispositions affecting the expression and metabolism of the amyloid-β protein precursor. Aluminum is a non-essential yet biologically-reactive metal implicated in the etiology of AD. Recent research has identified aluminum intricately and unequivocally associated with amyloid-β in senile plaques and, more tentatively, co-deposited with neuropil-like threads in the brains of a Colombian cohort of donors with fAD. Objective: Herein, we have assessed the co-localization of aluminum to immunolabelled phosphorylated tau to probe the potential preferential binding of aluminum to senile plaques or neurofibrillary tangles in the same Colombian kindred. …Methods: Herein, we have performed phosphorylated tau-specific immunolabelling followed by aluminum-specific fluorescence microscopy of the identical brain tissue sections via a sequential labelling method. Results: Aluminum was co-localized with immunoreactive phosphorylated tau in the brains of donors with fAD. While aluminum was predominantly co-located to neurofibrillary tangles in the temporal cortex, aluminum was more frequently co-deposited with cortical senile plaques. Conclusion: These data suggest that the co-deposition of aluminum with amyloid-β precedes that with neurofibrillary tangles. Extracellularly deposited amyloid-β may also be more immediately available to bind aluminum versus intracellular aggregates of tau. Therapeutic approaches to reduce tau have demonstrated the amelioration of its synergistic interactions with amyloid-β, ultimately reducing tau pathology and reducing neuronal loss. These data support the intricate associations of aluminum in the neuropathology of fAD, of which its subsequent reduction may further therapeutic benefits observed in ongoing clinical trials in vivo . Show more

Keywords: Aluminum in human brain tissue, amyloid-β , familial Alzheimer’s disease, neurofibrillary tangles, senile plaques, tau

DOI: 10.3233/ADR-210011

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 283-294, 2021