Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

Authors: Hack, Erica E. | Dubin, Joel A. | Fernandes, Myra A. | Costa, Sanduni M. | Tyas, Suzanne L.

Article Type: Research Article

Abstract: Background: Multilingualism is associated with enhanced executive function and may thus prevent cognitive decline and reduce the risk of dementia. Objective: To determine whether multilingualism is associated with delayed onset or reduced risk of dementia. Methods: Dementia was diagnosed according to DSM-IV criteria in the Nun Study, a longitudinal study of religious sisters aged 75+ years. Multilingualism was self-reported. Dementia likelihood was determined in 325 participants using discrete-time survival analysis; sensitivity analyses (n  = 106) incorporated additional linguistic measures (idea density and grammatical complexity). Results: Multilingualism did not delay the onset of dementia. However, participants …speaking four or more languages (but not two or three) were significantly less likely to develop dementia than monolinguals (OR = 0.13; 95% CI = 0.01, 0.65, adjusted for age, apolipoprotein E, and transition period). This significant protective effect of speaking four or more languages weakened (OR = 0.53; 95% CI = 0.06, 4.91) in the presence of idea density in models adjusted for education and apolipoprotein E. Conclusion: Linguistic ability broadly was a significant predictor of dementia, although it was written linguistic ability (specifically idea density) rather than multilingualism that was the strongest predictor. The impact of language on dementia may extend beyond number of languages spoken to encompass other indicators of linguistic ability. Further research to identify the characteristics of multilingualism most salient for risk of dementia could clarify the value, target audience, and design of interventions to promote multilingualism and other linguistic training as a strategy to reduce the risk of dementia and its individual and societal impacts. Show more

Keywords: Cognitive reserve, cohort studies, dementia, epidemiology, language, multilingualism, risk, survival analysis

DOI: 10.3233/JAD-181302

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Nudelman, Kelly N.H. | Lin, Jue | Lane, Kathleen A. | Nho, Kwangsik | Kim, Sungeun | Faber, Kelley M. | Risacher, Shannon L. | Foroud, Tatiana M. | Gao, Sujuan | Davis, Justin W. | Weiner, Michael W. | Saykin, Andrew J. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Although shorter telomeres have been associated with Alzheimer’s disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression. Objective: To investigate the association of telomere length change with AD diagnosis and progression. Methods: In 653 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere versus single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N = 1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used …to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre- to post-conversion to MCI or AD to telomere change in participants with stable diagnoses. Results: Shorter telomeres were associated with older age (Effect Size (ES) = –0.23) and male sex (ES = –0.26). Neither baseline T/S ratio (ES = –0.036) nor T/S ratio change (ES = 0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES = –0.186). Conclusions: Although AD compared to controls showed small, non-significant effects for baseline T/S ratio and T/S ratio shortening, we did observe a larger, though still non-significant effect for greater telomere shortening in converters compared to non-converters. Although our results do not support telomere shortening as a robust biomarker of AD progression, further investigation in larger samples and for subgroups of participants may be informative. Show more

Keywords: Alzheimer’s disease, longitudinal, progression, shortening, telomere

DOI: 10.3233/JAD-190010

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Jo, Hyunjin | Kim, Minkyeong | Park, Seongbeom | Park, Jong Eun | Cho, Soo Hyun | Kim, Seung Joo | Jang, Hyemin | Jung, Yong Hee | Kim, Junpyo | Na, Duk L. | Seo, Sang Won | Cho, Jin Whan | Kim, Hee Jin

Article Type: Short Communication

Abstract: Alzheimer’s disease patients with presenilin 1 (PSEN1 ) mutations commonly show parkinsonism in addition to dementia. Yet, whether these patients show dopaminergic deficit and response to L-dopa is largely unknown. We report a 43-year-old woman with a PSEN1 mutation (A434T) who showed right side dominant parkinsonism. As disease progressed, she developed bilateral parkinsonism which was markedly relieved by L-dopa. Amyloid (Florbetaben) positron-emission tomography (PET) showed cortical florbetaben uptake, relatively sparing the striatum. Initial dopamine transporter (FP-CIT) PET showed asymmetrically decreased FP-CIT uptake in the left striatum. We suggest that in Alzheimer’s disease patients with PSEN1 mutation, parkinsonism may …be relieved by L-dopa when it is associated with presynaptic dopaminergic deficit. Show more

Keywords: Alzheimer’s disease, FP-CIT PET, L-dopa, parkinsonism, presenilin 1

DOI: 10.3233/JAD-190469

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-6, 2019

Authors: Cullen, Stephanie | Borrie, Michael | Carroll, Susan | Sarquis-Adamson, Yanina | Pieruccini-Faria, Frederico | McKay, Scott | Montero-Odasso, Manuel

Article Type: Research Article

Abstract: Background: Poor dual-task gait (walking while performing a cognitively demanding task) has been linked to progression to dementia in older adults with mild cognitive impairment (MCI). However, many of these findings come from research environments; gait performance across the cognitive spectrum has not previously been studied in a clinical setting. Objective: To examine whether patients from a memory clinic show differences in usual and dual-task gait speed and dual-task cost (DTC) based on cognitive diagnosis. Methods: Patients in the Aging Brain Memory clinic (London, ON) performed a usual gait walk and three dual-task gait walks: counting …backwards by ones, naming animals, and counting backwards by seven (serial sevens) out loud. Patients were timed with a stopwatch over a six-meter path marked on the floor. One-way ANOVA was performed to evaluate associations between gait speed and DTC (% ) across groups. Results: One hundred ninety-four patients with subjective cognitive impairment (SCI; n  = 46), MCI (n  = 77), or dementia (n  = 71) were assessed. Performance in usual (p  <  0.001) and dual-task gait speed (counting gait p  <  0.001; naming animals p  <  0.001; serial sevens p  = 0.004) decreased across the spectrum of cognitive impairment. Patients with dementia had significantly higher DTC in both counting gait (p  = 0.02) and naming animals (p  = 0.04) conditions compared with patients with SCI and MCI, who had statistically similar DTC in all conditions. Conclusion: Dual-task gait performance significantly declines across the cognitive spectrum in a clinical setting. Dual-task gait testing may be used in conjunction with traditional assessments for diagnosing cognitive impairments. Show more

Keywords: Aging, cognition, dual-task gait, gait

DOI: 10.3233/JAD-181196

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2019

Authors: Calderón-Garcidueñas, Lilian | Kulesza, Randy J. | Mansour, Yusra | Aiello-Mora, Mario | Mukherjee, Partha S. | González-González, Luis Oscar

Article Type: Research Article

Abstract: A major impediment in early diagnosis of Alzheimer’s disease (AD) is the lack of robust non-invasive biomarkers of early brain dysfunction. Metropolitan Mexico City (MMC) children and young adults show hyperphosphorylated tau, amyloid-β, and α -synuclein within auditory and vestibular nuclei and marked dysmorphology in the ventral cochlear nucleus and superior olivary complex. Based on early involvement of auditory brainstem centers, we believe brainstem auditory evoked potentials can provide early AD biomarkers in MMC young residents. We measured brainstem auditory evoked potentials in MMC clinically healthy children (8.52±3.3 years) and adults (21.08±3.0 years, 42.48±8.5 years, and 71.2±6.4 years) compared to …clean air controls (6.5±0.7 years) and used multivariate analysis adjusting for age, gender, and residency. MMC children had decreased latency to wave I, delays in waves III and V, and longer latencies for interwave intervals, consistent with delayed central conduction time of brainstem neural transmission. In sharp contrast, young adults have significantly shortened interwave intervals I–III and I–V. By the 5th decade, wave V and interval I–V were significantly shorter, while the elderly cohort had significant delay in mean latencies and interwave intervals. Compensatory plasticity, increased auditory gain, cochlear synaptopathy, neuroinflammation, and AD continuum likely play a role in the evolving distinct auditory pathology in megacity urbanites. Understanding auditory central and peripheral dysfunction in the AD continuum evolving and progressing in pediatric and young adult populations may shed light on the complex mechanisms of AD development and help identify strong noninvasive biomarkers. AD evolving from childhood in air pollution environments ought to be preventable. Show more

Keywords: Air pollution, alpha synuclein, Alzheimer’s disease continuum, auditory nuclei, auditory plasticity, auditory gain, brainstem auditory evoked potentials, children, hyperphosphorylated tau, combustion and friction-derived nanoparticles

DOI: 10.3233/JAD-190405

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2019

Authors: Nocera, Joe R. | Arsik, Idil | Keskinocak, Pinar | Lepley-Flood, Amy | Lah, James J. | Levey, Allan I. | Esper, Greg J.

Article Type: Short Communication

Abstract: There is increasing interest in gait evaluations in clinical settings given the associations between gait and health outcomes. However, efforts examining implementation of gait evaluation in neurological clinics are lacking. Herein, gait implementation within a cognitive neurology clinic is presented. Over a 21-month period, a gait evaluation was collected on 81% of eligible patients (n  = 2,622; mean age 73.2±9.5; age range 49–94 years; 47% female). Patients and staff reported being satisfied with the gait assessment. These finding have implications for gait evaluations in clinical settings and for clinical research aimed at understanding the impact of cognitive symptomatology on gait.

Keywords: Cognition, dementia, gait, implementation

DOI: 10.3233/JAD-190106

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Mattos, Meghan K. | Sereika, Susan M. | Beach, Scott R. | Kim, Hyejin | Klunk, William E. | Knox, Melissa | Nadkarni, Neelesh K. | Parker, Lisa S. | Roberts, J. Scott | Schulz, Richard | Tamres, Lisa | Lingler, Jennifer H.

Article Type: Review Article

Abstract: As calls for transparency in human subjects research grow, investigators conducting Alzheimer’s disease (AD) biomarker research are increasingly required to consider their ethical obligations regarding the return of AD biomarker test results to research participants. When disclosing these test results to potentially vulnerable participants, investigators may face unique challenges to identify adverse events, particularly psychological events. The purpose of this paper is to describe our research team’s experience with developing and implementing a process for enhanced adverse event monitoring following the return of amyloid-β (Aβ) imaging results to research participants with mild cognitive impairment (MCI). Ethical and logistical considerations are …presented along with preliminary findings from an ongoing randomized controlled trial of Aβ imaging results disclosure in MCI. Following receipt of amyloid imaging results, participants underwent 14 days of adverse event monitoring using ecological momentary assessment (EMA), a strategy to capture health, behaviors, and mood as they occur in participants’ natural settings in real time. EMA telephone calls were placed at random during waking hours to screen for mood changes. Investigators were alerted for positive depression, anxiety, suicidal ideation screenings, or for two days of failed call attempts. Preliminary feasibility of twenty-four participants with MCI who participated in EMA mood assessments was successfully completed 83% (SD = 0.4) of the time over 14 days with no alerts for anxiety or depression screening items. EMA, when used with standard adverse event monitoring, is a promising and novel approach to maximize early detection of negative psychological reactions following AD biomarker results disclosed in research settings. Show more

Keywords: Amyloid, cognitive dysfunction, ecological momentary assessment, ethics, research subjects

DOI: 10.3233/JAD-190091

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2019

Authors: Brito-Aguilar, Rafael

Article Type: Review Article

Abstract:  Dementia has become a major public health concern around the world. Dementia risk factors are significantly different among countries. The number of new cases of dementia anticipated each year worldwide is almost 7.7 million, one new case every four seconds. There are 3.6 million (46%) new cases per year in Asia, 2.3 million (31%) in Europe, 1.2 million (16%) in the Americas, and 0.5 million (7%) in Africa. Latin American and Caribbean low and middle-income countries are at high risk. Air pollution is an important risk modifiable factor for dementia across the world, and the recent report of the Alzheimer’s …disease continuum in children and young adults residing in Metropolitan Mexico City along with the presence of cognitive impairment in 55% of the young adult population residing in Mexican cities with fine particulate matter concentrations above the current USEPA annual standard of 12 μg/m3 makes this a severe public health problem in progress. It is imperative to keep generating epidemiological data on dementia worldwide and their relationship with air pollutants to improve the strategies to face all the challenges associated with dementia and Alzheimer’s disease in particular. Alzheimer’s disease is a fatal disease, we have no cure, and we ought to invest in protecting our citizens by intervening in modifiable environmental factors. Show more

Keywords: Air pollution, Alzheimer’s disease, Alzheimer’s disease continuum, dementia, fine particulate matter, Latin America, Mexico, nanoparticles, prevalence

DOI: 10.3233/JAD-190177

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-5, 2019

Authors: Bernstein, Alissa | Harrison, Krista L. | Dulaney, Sarah | Merrilees, Jennifer | Bowhay, Angela | Heunis, Julia | Choi, Jeff | Feuer, Julie E. | Clark, Amy M. | Chiong, Winston | Lee, Kirby | Braley, Tamara L. | Bonasera, Stephen J. | Ritchie, Christine | Dohan, Dan | Miller, Bruce L. | Possin, Katherine L.

Article Type: Research Article

Abstract: Background: Care navigation is an approach to personalized care management and care coordination that can help overcome barriers to care. Care navigation has not been extensively studied in dementia, where health care workforce innovations are needed as a result of increasing disease prevalence and resulting costs to the health care system. Objective: To identify facilitators and barriers to care navigation in dementia and to assess dementia caregiver satisfaction with care navigation. Methods: Methods include qualitative research (interviews, focus groups, observations) with “Care Team Navigators” (CTNs) who were part of a dementia care navigation program, the Care …Ecosystem, and a quantitative survey with caregivers about their experiences with CTNs. Transcripts were analyzed to identify themes within the data. Results: CTNs identified the following facilitators to care navigation in dementia: working closely with caregivers; providing emotional support; tailoring education and resources; and coordinating with a clinical team around issues ranging from clinical questions to financial and legal decision-making. The barriers CTNS identified included burn-out, the progressive nature of the disease; coordinating with primary care providers; and identifying resources for dyads who are low-income, do not speak English, or live in rural areas. Caregivers across both sites highly rated CTNs, though satisfaction was higher among those in Nebraska and Iowa. Conclusions: Innovative approaches to care delivery in dementia are crucial. Care navigation offers a feasible model to train unlicensed people to deliver care as a way to deliver larger-scale support for the growing population of adults living with dementia and their caregivers. Show more

Keywords: Care navigation, caregivers, dementia, health care workforce

DOI: 10.3233/JAD-180957

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2019

Authors: Guo, Si | Xu, Jing-Jing | Wei, Na | Han, Jun-Ya | Xue, Rui | Xu, Po-Shi | Gao, Chuan-Yu

Article Type: Research Article

Abstract: Vascular dementia (VaD) is caused by chronic decreases in brain blood flow and accounts for 15–20% of dementia cases worldwide. In contrast to Alzheimer’s disease (AD), no effective drug treatments are currently available for VaD. Previous studies have suggested that oxidative stress and neuroinflammation in the brain play important roles in the pathogenesis of VaD. Honokiol (HKL) is a well-known bioactive and nutraceutical compound that can act as an antioxidant and anti-inflammatory molecule. HKL can protect against memory impairments in AD mouse models. In this study, we explored whether the application of HKL was also protective against the insult of …chronic cerebral hypoperfusion (CCH) in rats. We found that HKL supplementation prevented the memory impairments in the inhibitory avoidance step-down and Morris water maze tasks in CCH rats. HKL also suppressed the levels of oxidative stress and inflammation in CCH rats. Moreover, HKL prevented dendritic spines abnormalities in CCH rats. We also found that HKL inhibited the activity of GSK-3β , which may be critical for the neuroprotective activity of HKL. Thus, our study demonstrated the protective role of HKL in VaD. Show more

Keywords: GSK-3β, Honokiol, inflammation, memory impairments, oxidative stress, vascular dementia

DOI: 10.3233/JAD-190324

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2019