Journal of Alzheimer's Disease - Volume 82, issue 1

Authors: Yin, Xuejun | Xie, Qixing | Huang, Lieyu | Liu, Liming | Armstrong, Elizabeth | Zhen, Miaomiao | Ni, Jingnian | Shi, Jing | Tian, Jingzhou | Cheng, Wei

Article Type: Research Article

Abstract: Background: In China, family caregivers play a major role in caring for people living with Alzheimer’s disease (PLWAD), but little is known about the burden this creates. Objective: This study aimed to investigate the burden among family caregivers of PLWAD and the factors influenced it. Methods: Family caregivers of PLWAD were recruited from a hospital in China from January 2018 to July 2018. All data were collected online using the Chinese version of the Zarit Burden Interview (ZBI), and the participants’ sociodemographic and caregiving details were obtained. T -tests and Kruskal-Wallis H (K) tests were used …to compare ZBI scores between groups. Factors related to the caregiver psychological burden were analyzed using multiple linear regression analysis. Results: A total of 300 participants were assessed, of which 213 (71.00%) were female. More than half of the caregivers were the patient’s daughter (51.0%, n  = 153). The average ZBI score of the caregivers was 43.05 (13.42). The level of burden was influenced by age, the relationship of the caregiver to the patient, the severity of AD, the caregiver’s retirement status, the income level of the caregiver, and the caring time. Regression analysis showed that retired caregivers were more likely to have higher levels of burden and that burden increased with AD severity. Conclusion: Most family caregivers of PLWAD have a considerable caregiver psychological burden. The findings increase the understanding of factors that influence family caregiver burden, and pave the way for potential interventions, such as social support and caregiver empowerment, to reduce their burden. Show more

Keywords: Alzheimer’s disease, China, family caregivers, psychological burden, Zarit Burden Interview

DOI: 10.3233/JAD-210025

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 285-291, 2021

Authors: Duan, Wenna | Zhou, Grace D. | Balachandrasekaran, Arvind | Bhumkar, Ashish B. | Boraste, Paresh B. | Becker, James T. | Kuller, Lewis H. | Lopez, Oscar L. | Gach, H. Michael | Dai, Weiying

Article Type: Research Article

Abstract: Background: This is the first longitudinal study to assess regional cerebral blood flow (rCBF) changes during the progression from normal control (NC) through mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Objective: We aim to determine if perfusion MRI biomarkers, derived from our prior cross-sectional study, can predict the onset and cognitive decline of AD. Methods: Perfusion MRIs using arterial spin labeling (ASL) were acquired in 15 stable-NC, 14 NC-to-MCI, 16 stable-MCI, and 18 MCI/AD-to-AD participants from the Cardiovascular Health Study (CHS) cognition study. Group comparisons, predictions of AD conversion and time to conversion, and Modified …Mini-Mental State Examination (3MSE) from rCBF were performed. Results: Compared to the stable-NC group: 1) the stable-MCI group exhibited rCBF decreases in the right temporoparietal (p  = 0.00010) and right inferior frontal and insula (p  = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p  = 0.00062 and 0.0035). Compared to the NC-to-MCI group, the stable-MCI group exhibited a rCBF decrease in the right hippocampus region (p  = 0.0053). The baseline rCBF values in the posterior cingulate cortex (PCC) (p  = 0.0043), bilateral superior medial frontal regions (BSMF) (p  = 0.012), and left inferior frontal (p  = 0.010) regions predicted the 3MSE scores for all the participants at follow-up. The baseline rCBF in the PCC and BSMF regions predicted the conversion and time to conversion from MCI to AD (p  < 0.05; not significant after multiple corrections). Conclusion: We demonstrated the feasibility of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline. Show more

Keywords: Alzheimer’s disease, arterial spin labeling, cerebral blood flow, longitudinal study, mild cognitive impairment, prediction

DOI: 10.3233/JAD-210199

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 293-305, 2021

Authors: Zhang, Hongqiao | D’Agostino, Carla | Forman, Henry Jay | Cacciottolo, Mafalda | Thorwald, Max | Mack, William J. | Liu, Qinghai | Shkirkova, Kristina | Lamorie-Foote, Krista | Sioutas, Constantinos | Pirhadi, Milad | Mack, Wendy Jean | Morgan, Todd E. | Finch, Caleb E.

Article Type: Research Article

Abstract: Background: Air pollution is widely associated with accelerated cognitive decline at later ages and risk of Alzheimer’s disease (AD). Correspondingly, rodent models demonstrate the neurotoxicity of ambient air pollution and its components. Our studies with nano-sized particulate matter (nPM) from urban Los Angeles collected since 2009 have shown pro-amyloidogenic and pro-inflammatory responses. However, recent batches of nPM have diminished induction of the glutamate receptor GluA1 subunit, Iba1, TNFα , Aβ42 peptide, and white matter damage. The same methods, materials, and mouse genotypes were used throughout. Objective: Expand the nPM batch comparisons and evaluate archived brain samples to …identify the earliest change in nPM potency. Methods: Batches of nPM were analyzed by in vitro cell assays for NF-κ B and Nrf2 induction for comparison with in vivo responses of mouse brain regions from mice exposed to these batches, analyzed by PCR and western blot. Results: Five older nPM batches (2009–2017) and four recent nPM batches (2018, 2019) for NF-κ B and Nrf2 induction showed declines in nPM potency after 2017 that paralleled declines of in vivo activity from independent exposures in different years. Conclusion: Transcription-based in vitro assays of nPM corresponded to the loss of in vivo potency for inflammatory and oxidative responses. These recent decreases of nPM neurotoxicity give a rationale for evaluating possible benefits to the risk of dementia and stroke in Los Angeles populations. Show more

Keywords: Air pollution, Alzheimer’s disease, microglia, mouse brain, ultrafine particulate matter

DOI: 10.3233/JAD-201577

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 307-316, 2021

Authors: Tahmi, Mouna | Rippon, Brady | Palta, Priya | Sherwood, Greysi | Hernandez, Gabriela | Soto, Luisa | Ceballos, Fernando | Pardo, Michelle | Laing, Krystal | Igwe, Kay | He, Hengda | Teresi, Jeanne A. | Moreno, Herman | Razlighi, Qolamreza | Brickman, Adam M. | Luchsinger, José A.

Article Type: Research Article

Abstract: Background: The National Institute on Aging (NIA)/Alzheimer’s Association (AA) 2018 framework conceptualizes Alzheimer’s disease (AD) biologically. Evidence of brain amyloid by biomarkers defines AD pathologic change and the Alzheimer’s continuum. The presence of tau or neurodegeneration in the absence of amyloid defines non-AD pathologic change. Objective: To examine the relation of in vivo amyloid and neurodegeneration with verbal learning, one of the cognitive abilities affected early in AD, in late middle age. Methods: This was a cross-sectional study of amyloid and neurodegeneration biomarkers in a community-based cohort of 350 late-middle aged Hispanics without dementia (mean …age: 64.15±3.34; 72.0%women). Amyloid (A) was measured as global standardized uptake value ratio (SUVR) with 18 F-Florbetaben positron emission tomography (PET). Neurodegeneration (N) was ascertained as cortical thickness (CT) in AD signature areas using brain magnetic resonance imaging. We examined A/N continuously, categorically, by A/N profiles, and profile categories. The amyloid threshold for positivity was defined using the K means method. The CT threshold was defined as 2 standard deviations below the mean CT. Verbal learning was ascertained using total recall and delayed recall in the Buschke Selective Reminding test (SRT). Results: Higher cortical thickness was associated with higher performance in SRT delayed recall. Amyloid SUVR was not related to SRT performance. The low CT category was associated with lower performance in SRT delayed recall, while Amyloid categories were not related to any SRT score. The non-AD pathologic change group (A-N+) performed worse in SRT delayed recall compared to the Normal A/N profile group (A-N-). Conclusion: In late middle-aged Hispanics without dementia, non-AD pathologic change, but not the Alzheimer’s continuum, was related to verbal learning. Show more

Keywords: A/T/(N), amyloid, cognition, Hispanics, neurodegeneration, NIA-AA

DOI: 10.3233/JAD-201304

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 317-325, 2021

Authors: Barthelson, Karissa | Dong, Yang | Newman, Morgan | Lardelli, Michael

Article Type: Research Article

Abstract: Background: The most common cause of early-onset familial Alzheimer’s disease (EOfAD) is mutations in PRESENILIN 1 (PSEN1 ) allowing production of mRNAs encoding full-length, but mutant, proteins. In contrast, a single known frameshift mutation in PSEN1 causes familial acne inversa (fAI) without EOfAD. The molecular consequences of heterozygosity for these mutation types, and how they cause completely different diseases, remains largely unexplored. Objective: To analyze brain transcriptomes of young adult zebrafish to identify similarities and differences in the effects of heterozygosity for psen1 mutations causing EOfAD or fAI. Methods: RNA sequencing was performed …on mRNA isolated from the brains of a single family of 6-month-old zebrafish siblings either wild type or possessing a single, heterozygous EOfAD-like or fAI-like mutation in their endogenous psen1 gene. Results: Both mutations downregulate genes encoding ribosomal subunits, and upregulate genes involved in inflammation. Genes involved in energy metabolism appeared significantly affected only by the EOfAD-like mutation, while genes involved in Notch, Wnt and neurotrophin signaling pathways appeared significantly affected only by the fAI-like mutation. However, investigation of direct transcriptional targets of Notch signaling revealed possible increases in γ -secretase activity due to heterozygosity for either psen1 mutation. Transcriptional adaptation due to the fAI-like frameshift mutation was evident. Conclusion: We observed both similar and contrasting effects on brain transcriptomes of the heterozygous EOfAD-like and fAI-like mutations. The contrasting effects may illuminate how these mutation types cause distinct diseases. Show more

Keywords: Alzheimer’s disease, acne inversa, gamma-secretase, Presenilin 1, RNA-seq, zebrafish

DOI: 10.3233/JAD-210128

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 327-347, 2021

Authors: Fernández-Aguilar, Luz | Lora, Yaiza | Satorres, Encarnación | Ros, Laura | Melendez, Juan C. | Latorre, Jose Miguel

Article Type: Research Article

Abstract: Background: No studies have been conducted to date on the dimensional and discrete classification of emotions to study the emotional reactivity of older adults with Alzheimer’s disease (AD). Additionally, the presentation of film clips with affective content is currently one of the most effective and widely used Mood Induction Procedures (MIPS). However, it has been scarcely used in AD patients. Objective: Based on the dimensional and discrete models of emotion, this study examines the emotional reactivity of older adults with AD, using a popular set of film clips to induce emotions. Methods: We compared the responses …of older adults aged over 65-years with mild to moderate AD (n  = 15) and a healthy comparison group (n  = 17) to six target emotions: disgust, fear, anger, sadness, amusement, and tenderness. Results: The results showed significant differences in the reactivity of fear, anger, and sadness between AD patients and healthy comparison group. However, the responses of the two groups to positive film clips were similar. Only in the amusement clip did the AD participants show a higher intensity response. Conclusion: These findings suggest that the characteristic loss of cognitive abilities in AD is related to a reduction in the ability to react to emotional stimuli, especially negative ones. However, these abilities seem to be preserved when it comes to positive emotions. Future research is necessary to investigate whether the positivity effect is present in AD patients. Show more

Keywords: Dementia, emotion reactivity, film clip, mood induction, older adults

DOI: 10.3233/JAD-210233

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 349-360, 2021

Authors: Bernstein, Adam S. | Rapcsak, Steven Z. | Hornberger, Michael | Saranathan, Manojkumar | the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Increasing evidence suggests that thalamic nuclei may atrophy in Alzheimer’s disease (AD). We hypothesized that there will be significant atrophy of limbic thalamic nuclei associated with declining memory and cognition across the AD continuum. Objective: The objective of this work was to characterize volume differences in thalamic nuclei in subjects with early and late mild cognitive impairment (MCI) as well as AD when compared to healthy control (HC) subjects using a novel MRI-based thalamic segmentation technique (THOMAS). Methods: MPRAGE data from the ADNI database were used in this study (n  = 540). Healthy control (n  = 125), …early MCI (n  = 212), late MCI (n  = 114), and AD subjects (n  = 89) were selected, and their MRI data were parcellated to determine the volumes of 11 thalamic nuclei for each subject. Volumes across the different clinical subgroups were compared using ANCOVA. Results: There were significant differences in thalamic nuclei volumes between HC, late MCI, and AD subjects. The anteroventral, mediodorsal, pulvinar, medial geniculate, and centromedian nuclei were significantly smaller in subjects with late MCI and AD when compared to HC subjects. Furthermore, the mediodorsal, pulvinar, and medial geniculate nuclei were significantly smaller in early MCI when compared to HC subjects. Conclusion: This work highlights nucleus specific atrophy within the thalamus in subjects with early and late MCI and AD. This is consistent with the hypothesis that memory and cognitive changes in AD are mediated by damage to a large-scale integrated neural network that extends beyond the medial temporal lobes. Show more

Keywords: Alzheimer’s disease, Alzheimer’s disease neuroimaging initiative, mild cognitive impairment, Papez circuit, thalamic nuclei, thalamus, thalamus optimized multi-atlas segmentation, THOMAS

DOI: 10.3233/JAD-201583

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 361-371, 2021

Authors: McGrath, Ryan | Robinson-Lane, Sheria G. | Clark, Brian C. | Suhr, Julie A. | Giordani, Bruno J. | Vincent, Brenda M.

Article Type: Research Article

Abstract: Background: Dementia screening is an important step for appropriate dementia-related referrals to diagnosis and treat possible dementia. Objective: We sought to estimate the prevalence of no reported dementia-related diagnosis in a nationally representative sample of older Americans with a cognitive impairment consistent with dementia (CICD). Methods: The weighted analytical sample included 6,036,224 Americans aged at least 65 years old that were identified as having a CICD without history of stroke, cancers, neurological conditions, or brain damage who participated in at least one-wave of the 2010–2016 Health and Retirement Study. The adapted Telephone Interview of Cognitive Status …assessed cognitive functioning. Those with scores≤6 were considered as having a CICD. Healthcare provider dementia-related diagnosis was self-reported. Age, sex, educational achievement, and race and ethnicity were also self-reported. Results: The overall estimated prevalence of no reported dementia-related diagnosis for older Americans with a CICD was 91.4%(95%confidence interval (CI): 87.7%–94.1%). Persons with a CICD who identified as non-Hispanic black had a high prevalence of no reported dementia-related diagnosis (93.3%; CI: 89.8%–95.6%). The estimated prevalence of no reported dementia-related diagnosis was greater in males with a CICD (99.7%; CI: 99.6%–99.8%) than females (90.2%; CI: 85.6%–93.4%). Moreover, the estimated prevalence of no reported dementia-related diagnosis for non-high school graduates with a CICD was 93.5%(CI: 89.3%–96.1%), but 90.9%(CI: 84.7%–94.7%) for those with at least a high school education. Conclusion: Dementia screening should be encouraged during routine geriatric health assessments. Continued research that evaluates the utility of self-reported dementia-related measures is also warranted. Show more

Keywords: Aging, cognitive dysfunction, geriatric assessment, geriatrics, healthcare disparities

DOI: 10.3233/JAD-201212

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 373-380, 2021

Authors: Fieldhouse, Jay L.P. | Gossink, Flora T. | Feenstra, Thomas C. | de Boer, Sterre C.M. | Lemstra, Afina W. | Prins, Niels D. | Bouwman, Femke | Koene, Ted | Rhodius-Meester, Hanneke F.M. | Gillissen, Freek | Teunissen, Charlotte E. | van der Flier, Wiesje M. | Scheltens, Philip | Dols, Annemieke | Vijverberg, Everard G.B. | Pijnenburg, Yolande A.L.

Article Type: Research Article

Abstract: Background: Behavioral variant frontotemporal dementia (bvFTD) is generally considered a young-onset dementia, although age at onset is highly variable. While several studies indicate clinical differences regarding age at onset, no biomarker validated cohort studies with updated clinical criteria have been performed. Objective: We aimed to examine behavior, cognition, and mortality over the full age spectrum in a cohort of bvFTD patients with neuroimaging, genetic, or histopathological confirmation and exclusion of positive Alzheimer’s disease biomarkers or severe cerebrovascular damage. Methods: In total, 315 patients with a clinical diagnosis of probable or definite bvFTD were included from the …Amsterdam Dementia Cohort and grouped into quartiles by age-at-diagnosis. Neuropsychiatric symptoms and cognitive functioning were assessed with the neuropsychiatric inventory, the geriatric depression scale and a neuropsychological test battery. Data on mortality was obtained from the Dutch municipal register. Associations between age-at-diagnosis and clinical features and mortality risk were examined. Results: Age-at-diagnosis ranged from 26 to 85 years and established quartiles with mean ages of 52±6, 61±2, 66±2, and 74±3 years. In the total sample, 44.4%exceeded an age of 65 years at time of diagnosis. Earlier age-at-diagnosis was associated with more severe behavioral symptoms, while later age-at-diagnosis was associated with more severe memory impairment. Unexpectedly, mortality risk was not associated with age-at-diagnosis. Conclusion: In bvFTD, symptom profile is associated with age-at-diagnosis. This should be taken into account with regard to diagnostics, patient management, and trial design. Additionally, based on our sample, the prevalence of late-onset bvFTD is higher than generally thought. Show more

Keywords: Behavior, cognition, frontotemporal dementia, late-onset, mortality, young-onset

DOI: 10.3233/JAD-210179

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 381-390, 2021

Authors: Tawfik, Heba M. | Desouki, Rehab R. | Singab, Hamdi A. | Hamza, Sarah A. | El Said, Salma M.S.

Article Type: Research Article

Abstract: Background: Frailty affects up to 51%of the geriatric population in developing countries which leads to increased morbidity and mortality. Objective: To determine the association between pre-operative frailty through multidimentional assessment score, and the incidence of post-operative complications and to validate Robinson score in geriatric Egyptian patients undergoing elective cardiac surgery. Methods: We recruited 180 elderly participants aged 60 years old and above, who underwent elective cardiac surgery. They were divided into frail, pre-frail, and non-frail groups after application of Robinson score (which includes cognitive and functional and fall risk assessment, number of comorbidities, and different laboratory …data). Type and duration of operations and the presence and severity of complications at days 3 and 7 post-surgery, and the 30-day readmission rate were assessed. Results: Operation duration and the occurrence of postoperative complications at days 3 and 7 were lowest in non-frail and highest in the frail group (p  < 0.001 for both). Length of hospital stay and 30-day readmission rate also increased in the frail group. A positive, moderate correlation between frailty and blood transfusion (r  = 0.405) and functional dependence (r  = 0.552) was found at day-3 post-surgery. Finally, logistic regression analysis identified a 6-fold increase in postoperative complications in the frail group (OR = 6). Conclusion: Preoperative frailty was associated with higher incidence of postoperative complications among geriatric patients undergoing elective cardiac surgery. Frailty assessment by Robinson score can be considered as an accurate tool to predict postoperative complications during preoperative assessment of elderly patients. Show more

Keywords: Cardiac surgery, frailty, geriatric, postoperative complications, Robinson score

DOI: 10.3233/JAD-201479

Citation: Journal of Alzheimer's Disease, vol. 82, no. 1, pp. 391-399, 2021