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

Authors: Wang, Ge | Li, Wei

Article Type: Research Article

Abstract: Background: It is inconclusive on how sex affects the risk of developing mild cognitive impairment (MCI) or dementia. Objective: To investigate how sex affects the risk of developing MCI or dementia. Methods: A secondary data analysis was performed on data collected from participants enrolled at Alzheimer’s Disease Research Centers funded by National Institute on Aging. There were two inclusion criteria: 1) participants were free of dementia at the baseline visit; 2) every participant must have at least one follow-up visit. A Cox proportional hazards model was used to investigate how sex affects the risk of developing …cognitive impairments. Results: During a follow-up period of more than 10 years, male participants had a slightly higher incidence than female participants for either MCI or dementia. Not surprisingly, a higher prevalence was observed in male than female participants for either MCI or dementia. However, male participants had a higher mortality rate than their female counterparts. Conclusion: The male sex is associated with a higher risk for developing cognitive impairments along the aging process. Show more

Keywords: Dementia, incidence, mild cognitive impairment, prevalence, sex

DOI: 10.3233/ADR-200275

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 1-6, 2021

Authors: Shin, Jisu | Yang, Seung-Hoon | Du, Young Eun | Park, Keunwan | Kim, DaWon | Shin, Daniel | Kim, Jungwoo | Kim, Seong-Hwan | Kim, Yun Kyung | Shin, Jongheon | Oh, Dong-Chan | Kim, YoungSoo

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is characterized by the aggregation of two pathological proteins, amyloid-β (Aβ) and tau, leading to neuronal and cognitive dysfunction. Clearance of either Aβ or tau aggregates by immunotherapy has become a potential therapy, as these aggregates are found in the brain ahead of the symptom onset. Given that Aβ and tau independently and cooperatively play critical roles in AD development, AD treatments might require therapeutic approaches to eliminate both aggregates together. Objective: We aimed to discover a chemical drug candidate from natural sources for direct dissociation of both insoluble Aβ and tau aggregates through …in vitro assessments. Methods: We isolated four borrelidin chemicals from a saltern-derived halophilic actinomycete strain of rare genus Nocardiopsis and simulated their docking interactions with Aβ fibrils. Then, anti-cytotoxic, anti-Aβ, and anti-tau effects of borrelidins were examined by MTT assays with HT22 hippocampal cell line, thioflavin T assays, and gel electrophoresis. Results: When HT22 cells were exposed to Aβ aggregates, the treatment of borrelidins alleviates the Aβ-induced toxicity. These anti-cytotoxic effects can be derived from the inhibitory functions of borrelidins against the Aβ aggregation as shown in thioflavin T and gel electrophoretic analyses. Among them, especially borrelidin, which exhibits the highest probability of docking, not only dissociates Aβ aggregates but also directly regulates tau aggregation. Conclusion: Borrelidin dissociates insoluble Aβ and tau aggregates together and our findings support the view that it is possible to develop an alternative chemical approach mimicking anti-Aβ or anti-tau immunotherapy for clearance of both aggregates. Show more

Keywords: Alzheimer’s disease, amyloid-β, borrelidin, natural products, tau

DOI: 10.3233/ADR-200247

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 7-13, 2021

Authors: Chávez-Fumagalli, Miguel A. | Shrivastava, Pallavi | Aguilar-Pineda, Jorge A. | Nieto-Montesinos, Rita | Del-Carpio, Gonzalo Davila | Peralta-Mestas, Antero | Caracela-Zeballos, Claudia | Valdez-Lazo, Guillermo | Fernandez-Macedo, Victor | Pino-Figueroa, Alejandro | Vera-Lopez, Karin J. | Lino Cardenas, Christian L.

Article Type: Research Article

Abstract: Background: The present systematic review and meta-analysis of diagnostic test accuracy summarizes the last three decades in advances on diagnosis of Alzheimer’s disease (AD) in developed and developing countries. Objective: To determine the accuracy of biomarkers in diagnostic tools in AD, for example, cerebrospinal fluid, positron emission tomography (PET), and magnetic resonance imaging (MRI), etc. Methods: The authors searched PubMed for published studies from 1990 to April 2020 on AD diagnostic biomarkers. 84 published studies were pooled and analyzed in this meta-analysis and diagnostic accuracy was compared by summary receiver operating characteristic statistics. Results: …Overall, 84 studies met the criteria and were included in a meta-analysis. For EEG, the sensitivity ranged from 67 to 98%, with a median of 80%, 95% CI [75, 91], tau-PET diagnosis sensitivity ranged from 76 to 97%, with a median of 94%, 95% CI [76, 97]; and MRI sensitivity ranged from 41 to 99%, with a median of 84%, 95% CI [81, 87]. Our results showed that tau-PET diagnosis had higher performance as compared to other diagnostic methods in this meta-analysis. Conclusion: Our findings showed an important discrepancy in diagnostic data for AD between developed and developing countries, which can impact global prevalence estimation and management of AD. Also, our analysis found a better performance for the tau-PET diagnostic over other methods to diagnose AD patients, but the expense of tau-PET scan seems to be the limiting factor in the diagnosis of AD in developing countries such as those found in Asia, Africa, and Latin America. Show more

Keywords: Alzheimer’s disease, diagnosis, meta-analysis, systematic review

DOI: 10.3233/ADR-200263

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 15-30, 2021

Authors: Stites, Shana D. | Largent, Emily A. | Johnson, Rebecca | Harkins, Kristin | Karlawish, Jason

Article Type: Research Article

Abstract: Background: As a result of caring for a person with dementia, caregivers of persons with Alzheimer’s disease (AD) may be uniquely aware of public stigma for persons with AD. Objective: The purpose of this study was to compare self-identified caregivers and non-caregivers’ expectations of public stigma experienced by persons living with dementia. Methods: Analysis of data from a survey of 910 adults (median age = 49 years) who read a vignette about a man with mild stage dementia. Multivariable ordered logistic regression was used to examine how AD caregiver status associated with responses on a modified Family …Stigma in Alzheimer’s Disease Scale (FS-ADS). Results: 9%(n  = 82) of respondents self-identified as a current or former primary caregiver of a person with AD, about the same as the national estimate of informal caregivers (8.8%). Compared to non-caregivers, AD caregivers were more likely to report stronger reactions on all seven domains of the FS-ADS (all p  <  0.05). As compared to AD caregivers with less factual knowledge about caregiving, AD caregivers with more knowledge expected the person with dementia to experience less social distance (p  <  0.05). In addition, female AD caregivers reported fewer negative aesthetic attributions than male AD caregivers (p  <  0.05). Conclusion: Compared to non-caregivers, respondents who self-identified as an AD caregiver gave responses that suggest they perceived more stigma of dementia among members of the public. Their reactions were attenuated by AD knowledge and being female. The findings have key implications for interventions to reduce AD stigma. Show more

Keywords: Alzheimer’s disease, caregivers, public survey, stigma

DOI: 10.3233/ADR-200206

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 31-39, 2021

Authors: Andrews, Murray | Ross, Ryan | Malhotra, Atul | Ancoli-Israel, Sonia | Brewer, James B. | Banks, Sarah J. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: The increasing prevalence of Alzheimer’s disease (AD) and lack of effective medications has led to a need to identify modifiable risk factors as targets for interventions. Objective: In this cross-sectional study, we sought to determine whether worse sleep quality is associated with increased pathological tau, and whether this relationship is affected by amyloid pathology. Methods: 66 male participants underwent Florbetapir (AV45) positron emission tomography (PET) and Flortaucipir (FTP) PET and completed the Pittsburgh Sleep Quality Index questionnaire (PSQI) as part of the Department of Defense Alzheimer’s Disease Neuroimaging Initiative, a multicenter study collecting data from …Vietnam War veterans, some of whom have a history of post-traumatic stress disorder, or non-penetrating traumatic brain injury. AV45 PET was used to determine the presence of significant amyloid pathology. We used regression models to determine the effects of amyloid pathology and PSQI on tau deposition in brain regions associated with Braak stages. Results: Among the 66 participants, 14 individuals were amyloid positive (21%) and 52 were amyloid negative (79%). In regions associated with Braak stages III-IV, there was a significant interaction of amyloid status on PSQI (β= 0.04, p  = 0.003) with higher PSQI correlating with higher FTP SUVr in amyloid-positive individuals only (β= 0.031, p  = 0.005). Conclusion: Our study found that an AD profile of tau deposition was associated with an interaction between self-reported sleep quality and amyloid pathology such that worse self-reported sleep was related to higher tau in regions usually associated with AD progression, but only in individuals with high cerebral amyloid deposition. Show more

Keywords: Amyloid, mild cognitive impairment, positron emission tomography, preclinical AD, sleep, tau

DOI: 10.3233/ADR-200245

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 41-48, 2021

Authors: Lehrer, Steven | Rheinstein, Peter H.

Article Type: Research Article

Abstract: Background: Cognitive problems are common in breast cancer patients. The apolipoprotein E4 (APOE4 ) gene, a risk factor for Alzheimer’s disease (AD), may be associated with cancer-related cognitive decline. Objective: To further evaluate the effects of the APOE4 allele, we studied a cohort of patients from the UK Biobank (UKB) who had breast cancer; some also had AD. Methods: Our analysis included all subjects with invasive breast cancer. Single nucleotide polymorphism (SNP) data for rs 429358 and rs 7412 was used to determine APOE genotypes. Cognitive function as numeric memory was assessed with an …online test (UKB data field 20240). Results: We analyzed data from 2,876 women with breast cancer. Of the breast cancer subjects, 585 (20%) carried the APOE4 allele. Numeric memory scores were significantly lower in APOE4 carriers and APOE4 homozygotes than non-carriers (p  = 0.046). 34 breast cancer subjects (1.1%) had AD. There was no significant difference in survival among genotypes ɛ 3/ɛ 3, ɛ 3/ɛ 4, and ɛ 4/ɛ 4. Conclusion: UKB data suggest that cognitive problems in women with breast cancer are, for the most part, mild, compared with other sequelae of the disease. AD, the worst cognitive problem, is relatively rare (1.1%) and, when it occurs, APOE genotype has little impact on survival. Show more

Keywords: APOE , chemobrain, dementia, heterozygote

DOI: 10.3233/ADR-200266

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 49-53, 2021

Authors: Falck, Ryan S. | Crockett, Rachel A. | Davis, Jennifer C. | Khan, Karim M. | Liu-Ambrose, Teresa

Article Type: Research Article

Abstract: Background: Poor sleep is common among older adults at risk for dementia and may be due to circadian dysregulation. Light is the most important external stimulus to the circadian clock and bright light therapy (BLT) has been used for >20 years to help realign circadian rhythms. However, the ability of field methods (e.g., actigraphy) to accurately determine the type and intensity of light is unknown. Objective: We examined the ability of the MotionWatch8 (MW8) light sensor to determine: 1) light versus dark, 2) electrical light versus daylight, and 3) device-based BLT versus light which was not BLT. …Methods: We tested the MW8 under 17 daily light scenarios. Light exposure data was collected for 5 minutes during each scenario. Concurrently, we measured light exposure using the LT40 Light Meter, a sensitive measure of light intensity. We then developed individual cut-points using receiver operator characteristics analyses to determine optimal MW8 cut-points for 1) light versus dark; 2) electrical light versus daylight; and 3) light from a BLT box versus light which was not BLT. Bland-Altman plots tested the precision of the MW8 compared to the LT40. Results: The MW8 accurately discriminated light versus dark (>32 lux), and electrical light versus daylight (<323 lux). However, the MW8 had poor accuracy for 1) discriminating BLT from light which was not BLT; and 2) low precision compared to the LT40. Conclusion: The MW8 appears to be able to discern light versus dark and electrical light versus daylight; however, there remains a need for accurate field methods capable of measuring light exposure. Show more

Keywords: Actigraphy, light, luxometer, measurement, sleep

DOI: 10.3233/ADR-200242

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 55-63, 2021

Authors: Dake, Manmohi D. | De Marco, Matteo | Blackburn, Daniel J. | Wilkinson, Iain D. | Remes, Anne | Liu, Yawu | Pikkarainen, Maria | Hallikainen, Merja | Soininen, Hilkka | Venneri, Annalena

Article Type: Research Article

Abstract: Background: How the relationship between obesity and MRI-defined neural properties varies across distinct stages of cognitive impairment due to Alzheimer’s disease is unclear. Objective: We used multimodal neuroimaging to clarify this relationship. Methods: Scans were acquired from 47 patients clinically diagnosed with mild Alzheimer’s disease dementia, 68 patients with mild cognitive impairment, and 57 cognitively healthy individuals. Voxel-wise associations were run between maps of gray matter volume, white matter integrity, and cerebral blood flow, and global/visceral obesity. Results: Negative associations were found in cognitively healthy individuals between obesity and white …matter integrity and cerebral blood flow of temporo-parietal regions. In mild cognitive impairment, negative associations emerged in frontal, temporal, and brainstem regions. In mild dementia, a positive association was found between obesity and gray matter volume around the right temporoparietal junction. Conclusion: Obesity might contribute toward neural tissue vulnerability in cognitively healthy individuals and mild cognitive impairment, while a healthy weight in mild Alzheimer’s disease dementia could help preserve brain structure in the presence of age and disease-related weight loss. Show more

Keywords: Alzheimer’s disease, body mass index, neuroimaging, overweight

DOI: 10.3233/ADR-200267

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 65-77, 2021

Authors: Olsen, Ingar

Article Type: Research Article

Abstract: Iron accumulates in the brain of subjects with Alzheimer’s disease (AD). Here it promotes the aggregation of amyloid-β plaques in which it is abundant. Iron induces amyloid-β neurotoxicity by damaging free radicals and causing oxidative stress in brain areas with neurodegeneration. It can also bind to tau in AD and enhance the toxicity of tau through co-localization with neurofibrillary tangles and induce accumulation of these tangles. Porphyromonas gingivalis is a key oral pathogen in the widespread biofilm-induced disease “chronic” periodontitis, and recently, has been suggested to have an important role in the pathogenesis of AD. P. gingivalis has …an obligate requirement for iron. The current paper suggests that P. gingivalis seeks the AD brain, where it has been identified, to satisfy this need. If this is correct, iron chelators binding iron could have beneficial effects in the treatment of AD. Indeed, studies from both animal AD models and humans with AD have indicated that iron chelators, e.g., lactoferrin, can have such effects. Lactoferrin can also inhibit P. gingivalis growth and proteinases and its ability to form biofilm. Show more

Keywords: Biofilm, brain, immunity, iron dysregulation, iron requirement, senescence

DOI: 10.3233/ADR-200272

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 79-86, 2021

Authors: Zenuni, Henri | Grillo, Piergiorgio | Sancesario, Giulia Maria | Bernardini, Sergio | Mercuri, Nicola Biagio | Schirinzi, Tommaso

Article Type: Short Communication

Abstract: Systemic comorbidity precipitates the risk for dementia. To comprehend the underlying mechanisms into a therapeutic perspective, we analyzed how comorbidity affects neurodegeneration-related cerebrospinal fluid (CSF) biomarkers of 55 cognitively intact subjects. The Charson Comorbidity Index (CCI) was correlated with CSF amyloid-β42 (Aβ42 ), amyloid-β40 , total-tau, 181-phosphorylated-tau (p-tau), the Aβ42 /p-tau ratio, neurogranin, and lactate. The age-related brain lesions at imaging were also considered. CCI had a raw association with Aβ42 /p-tau and p-tau, and a stronger, age-independent correlation with lactate. These preliminary findings suggested that, in normal subjects, systemic comorbidity might increase CNS oxidative stress and, together with …aging, contribute to develop an Alzheimer’s disease-like biochemical profile. Show more

Keywords: Cerebrospinal fluid biomarkers, comorbidity, neurodegeneration, neuroprotection, oxidative stress

DOI: 10.3233/ADR-200280

Citation: Journal of Alzheimer's Disease Reports, vol. 5, no. 1, pp. 87-92, 2021