Journal of Alzheimer's Disease - Volume 71, issue 1

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. 71, no. 1, pp. 1-5, 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. 71, no. 1, pp. 7-13, 2019

Authors: Verwey, Nicolaas A. | Teunissen, Charlotte E. | Hoozemans, Jeroen J.M. | Rozemuller, Annemieke J.M. | Scheltens, Philip | Pijnenburg, Yolande A.L.

Article Type: Short Communication

Abstract: To investigate amyloid-β (Aβ) in frontotemporal dementia (FTD), cerebrospinal fluid (CSF) Aβ38 , Aβ40 , and Aβ42 in frontotemporal lobar degeneration (FTLD; N = 18 genetically and/or pathologically confirmed and N = 8 FTD with concomitant amyotrophic lateral sclerosis) were compared with Alzheimer’s disease (AD; pathological or Pittsburgh-compound-B Positron-emission-tomography (PIB-PET) positive; N = 25) and controls (N = 24). For all the Aβ subtypes, group difference was seen and post-hoc analysis revealed lower levels in FTLD compared to controls (p ≤0.05). Aβ42/40 ratio showed no difference between FTLD and controls; however, a difference was seen between AD versus FTLD (p  < 0.01). This is an intriguing …finding, suggesting a possible role of Aβ in FTLD pathogenesis. Show more

Keywords: Alzheimer’s disease, amyloid, frontotemporal dementia, frontotemporal lobar degeneration

DOI: 10.3233/JAD-190344

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 15-20, 2019

Authors: Ruthirakuhan, Myuri | Herrmann, Nathan | Andreazza, Ana C. | Verhoeff, Nicolaas Paul L.G. | Gallagher, Damien | Black, Sandra E. | Kiss, Alex | Lanctôt, Krista L.

Article Type: Research Article

Abstract: Background: Agitation is a prevalent and difficult-to-treat symptom of Alzheimer’s disease (AD). The endocannabinoid system (ECS) has been a target of interest for the treatment of agitation. However, ECS signaling may interact with AD-related changes in brain cholesterol metabolism. Elevated brain cholesterol, reflected by reduced serum 24-S-hydroxycholesterol (24S-OHC), is associated with reduced membrane fluidity, preventing ligand binding to cannabinoid receptor 1. Objective: To assess whether 24S-OHC was associated with agitation severity and response to nabilone. Methods: 24S-OHC was collected from AD patients enrolled in a clinical trial on nabilone at the start and end of each …phase. This allowed for the cross-sectional and longitudinal investigation between 24S-OHC and agitation (Cohen Mansfield Agitation Inventory, CMAI). Post-hoc analyses included adjustments for baseline standardized Mini-Mental Status Exam (sMMSE), and analyses with CMAI subtotals consistent with the International Psychogeriatric Association (IPA) definition for agitation (physical aggression and nonaggression, and verbal aggression). Results: 24S-OHC was not associated with CMAI scores cross-sectionally or longitudinally, before and after adjusting for baseline sMMSE. However, 24S-OHC was associated with greater CMAI IPA scores at baseline (F(1,36) = 4.95, p  = 0.03). In the placebo phase only, lower 24S-OHC at baseline was associated with increases in CMAI IPA scores (b = –35.2, 95% CI –65.6 to –5.0, p  = 0.02), and decreases in 24S-OHC were associated with increases in CMAI IPA scores (b = –20.94, 95% CI –57.9 to –4.01, p  = 0.03). Conclusion: 24S-OHC was associated with agitation severity cross-sectionally, and longitudinally in patients with AD. However, 24S-OHC did not predict treatment response, and does not change over time with nabilone. Show more

Keywords: Alzheimer’s disease, behavioral symptoms, biomarkers, geriatric psychiatry

DOI: 10.3233/JAD-190202

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 21-31, 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. 71, no. 1, pp. 33-43, 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 S. | 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. 71, no. 1, pp. 45-55, 2019

Authors: Arendash, Gary | Cao, Chuanhai | Abulaban, Haitham | Baranowski, Rob | Wisniewski, Gary | Becerra, Lino | Andel, Ross | Lin, Xiaoyang | Zhang, Xiaolin | Wittwer, David | Moulton, Jay | Arrington, John | Smith, Amanda

Article Type: Research Article

Abstract: Background: Small aggregates (oligomers) of the toxic proteins amyloid-β (Aβ) and phospho-tau (p-tau) are essential contributors to Alzheimer’s disease (AD). In mouse models for AD or human AD brain extracts, Transcranial Electromagnetic Treatment (TEMT) disaggregates both Aβ and p-tau oligomers, and induces brain mitochondrial enhancement. These apparent “disease-modifying” actions of TEMT both prevent and reverse memory impairment in AD transgenic mice. Objective: To evaluate the safety and initial clinical efficacy of TEMT against AD, a comprehensive open-label clinical trial was performed. Methods: Eight mild/moderate AD patients were treated with TEMT in-home by their caregivers for 2 …months utilizing a unique head device. TEMT was given for two 1-hour periods each day, with subjects primarily evaluated at baseline, end-of-treatment, and 2 weeks following treatment completion. Results: No deleterious behavioral effects, discomfort, or physiologic changes resulted from 2 months of TEMT, as well as no evidence of tumor or microhemorrhage induction. TEMT induced clinically important and statistically significant improvements in ADAS-cog, as well as in the Rey AVLT. TEMT also produced increases in cerebrospinal fluid (CSF) levels of soluble Aβ1-40 and Aβ1-42 , cognition-related changes in CSF oligomeric Aβ, a decreased CSF p-tau/Aβ1-42 ratio, and reduced levels of oligomeric Aβ in plasma. Pre- versus post-treatment FDG-PET brain scans revealed stable cerebral glucose utilization, with several subjects exhibiting enhanced glucose utilization. Evaluation of diffusion tensor imaging (fractional anisotropy) scans in individual subjects provided support for TEMT-induced increases in functional connectivity within the cognitively-important cingulate cortex/cingulum. Conclusion: TEMT administration to AD subjects appears to be safe, while providing cognitive enhancement, changes to CSF/blood AD markers, and evidence of stable/enhanced brain connectivity. Show more

Keywords: Amyloid-β, brain electromagnetic waves, cognitive enhancement, FDG-PET, functional MRI

DOI: 10.3233/JAD-190367

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 57-82, 2019

Authors: Nguyen, Tuan Anh | Gilmartin-Thomas, Julia | Tan, Edwin Chin Kang | Kalisch-Ellett, Lisa | Eshetie, Tesfahun | Gillam, Marianne | Reeve, Emily

Article Type: Research Article

Abstract: Background: Medication use in people with dementia and/or cognitive impairment (PWD/CI) is challenging. As medication experts, pharmacists have an important role in improving care of this vulnerable population. Objective: Systematically review evidence for the effectiveness of pharmacist-led interventions on quality use of medicines, quality of life, and health outcomes of PWD/CI. Methods: A systematic review was conducted using MEDLINE, EMBASE, PsycINFO, Allied and Complementary Medicine (AMED) and Cumulative index to Nursing and Allied Health Literature (CINAHL) databases from conception to 20 March 2017. Full articles published in English were included. Data were synthesized using a narrative …approach. Results: Nine studies were eligible for inclusion. All studies were from high-income countries and assessed pharmacist-led medication management services. There was great variability in the content and focus of services described and outcomes reported. Pharmacists were found to provide a number of cognitive services including medication reconciliation, medication review, and medication adherence services. These services were generally effective with regards to improving quality use of medicines and health outcomes for PWD/CI and their caregivers, and for saving costs to the healthcare system. Pharmacist-led medication and dementia consultation services may also improve caregiver understanding of dementia and the different aspects of pharmacotherapy, thus improving medication adherence. Conclusion: Emerging evidence suggests that pharmacist-led medication management services for PWD/CI may improve outcomes. Future research should confirm these findings using more robust study designs and explore additional roles that pharmacists could undertake in the pursuit of supporting PWD/CI. Show more

Keywords: Cognitive impairment, dementia, health outcome, impact, intervention, pharmacist, quality of life, role, systematic review

DOI: 10.3233/JAD-190162

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 83-96, 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. 71, no. 1, pp. 97-108, 2019

Authors: Reas, Emilie T. | Laughlin, Gail A. | Bergstrom, Jaclyn | Kritz-Silverstein, Donna | McEvoy, Linda K.

Article Type: Research Article

Abstract: Background: Although physical activity has been associated with better cognitive function and reduced dementia risk, its association with cognitive decline in normal aging remains uncertain. Objective: To determine whether physical activity in youth and older age are associated with age-related cognitive change. Methods: Over a period of 27 years, 2,027 community-dwelling adults (mean age 73.5; 60% women) of the Rancho Bernardo Study of Healthy Aging completed up to seven cognitive assessments, including tests of global cognitive function, executive function, verbal fluency, and episodic memory. At each visit, participants reported concurrent physical activity. At baseline (1988– 1992), …participants additionally reported physical activity as a teenager and at age 30. For each age period, participants were classified as regularly active (3+ times/week) or inactive. Results: Associations between concurrent physical activity and better cognitive function were stronger with advancing age on all tests, even after accounting for education, health, and lifestyle factors, as well as survival differences (p s < 0.05). Baseline physical activity did not predict rates of cognitive decline (p s > 0.40). Individuals who were physically active at age 30 and older age maintained the highest global cognitive function with advancing age (p  = 0.002). Conclusion: Regular physical activity is associated with better cognitive function with advancing age. Physical activity in young adulthood may contribute to cognitive reserve, which together with physical activity in later years, may act to preserve cognitive function with age. Show more

Keywords: Aging, cognitive decline, cognitive reserve, exercise, longitudinal study, physical activity

DOI: 10.3233/JAD-190491

Citation: Journal of Alzheimer's Disease, vol. 71, no. 1, pp. 109-118, 2019