Journal of Alzheimer's Disease - Volume 78, issue 3

Authors: Loupy, Kelsey M. | Lee, Thomas | Zambrano, Cristian A. | Elsayed, Ahmed I. | D’Angelo, Heather M. | Fonken, Laura K. | Frank, Matthew G. | Maier, Steven F. | Lowry, Christopher A.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is an inflammatory neurodegenerative disease that may be associated with prior bacterial infections. Microbial “old friends” can suppress exaggerated inflammation in response to disease-causing infections or increase clearance of pathogens such as Mycobacterium tuberculosis , which causes tuberculosis (TB). One such “old friend” is Mycobacterium vaccae NCTC 11659, a soil-derived bacterium that has been proposed either as a vaccine for prevention of TB, or as immunotherapy for the treatment of TB when used alongside first line anti-TB drug treatment. Objective: The goal of this study was to use a hypothesis generating approach to …explore the effects of M. vaccae on physiological changes in the plasma and cerebrospinal fluid (CSF). Methods: Liquid chromatography-tandem mass spectrometry-based proteomics were performed in plasma and CSF of adult male rats after immunization with a heat-killed preparation of M. vaccae NCTC 11659 or borate-buffered saline vehicle. Gene enrichment analysis and analysis of protein-protein interactions were performed to integrate physiological network changes in plasma and CSF. We used RT-qPCR to assess immune and metabolic gene expression changes in the hippocampus. Results: In both plasma and CSF, immunization with M. vaccae increased proteins associated with immune activation and downregulated proteins corresponding to lipid (including phospholipid and cholesterol) metabolism. Immunization with M. vaccae also increased hippocampal expression of interleukin-4 (IL-4) mRNA, implicating anti-inflammatory effects in the central nervous system. Conclusion: M. vaccae alters host immune activity and lipid metabolism. These data are consistent with the hypothesis that microbe-host interactions may protect against possible infection-induced, inflammation-related cognitive impairments. Show more

Keywords: Alzheimer’s disease, ApoA-I, ApoC-II, cerebrospinal fluid, inflammation, lipid metabolism, mycobacteria, neurodegenerative disorder, neuroimmunomodulation, proteomics

DOI: 10.3233/JAD-200568

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 965-987, 2020

Authors: Gibson, Gary E. | Luchsinger, José A. | Cirio, Rosanna | Chen, Huanlian | Franchino-Elder, Jessica | Hirsch, Joseph A. | Bettendorff, Lucien | Chen, Zhengming | Flowers, Sarah A. | Gerber, Linda M. | Grandville, Thomas | Schupf, Nicole | Xu, Hui | Stern, Yaakov | Habeck, Christian | Jordan, Barry | Fonzetti, Pasquale

Article Type: Research Article

Abstract: Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer’s disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation. Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine. Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer’s …Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome. Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p  = 0.125). Worsening in CDR was 77% lower (p  = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOE ɛ 4 non-carriers. Benfotiamine significantly reduced increases in AGE (p  = 0.044), and this effect was stronger in the APOE ɛ 4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p  = 0.002). Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD. Show more

Keywords: Advanced glycation endproducts, Alzheimer’s disease, benfotiamine, glucose, inflammation, oxidative stress

DOI: 10.3233/JAD-200896

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 989-1010, 2020

Authors: Werner, Perla | AboJabel, Hanan

Article Type: Research Article

Abstract: Background Engagement in behaviors aimed at reducing the risk of developing dementia is a leading recommendation in most National Dementia Strategy programs. Objective: In an effort to advance knowledge regarding the implementation of this recommendation, the current study examined the perceptions and engagement of the adult population in Israel regarding behaviors aimed at reducing the risk of developing dementia, and its correlates. Methods: A cross-sectional survey was conducted among 502 Israeli adults aged 40 and over. Approximately half of the participants (51.2%) were female, and the majority (80.1%) were Jewish. Results: Overall, while the …percentage of participants reporting that the examined activities were important for brain health was moderate, percentages reporting engaging in these behaviors were low. The most important correlate of engagement in health behaviors was participants’ perceptions about the importance of these behaviors for their brain health. Increased age, being Jewish, and enhanced perceived susceptibility to develop dementia were also significantly associated with increased engagement in behaviors to reduce the risk of dementia. Conclusion: The results of this study emphasize the need to develop intervention programs aimed at promoting engagement in behaviors to reduce the risk of dementia development. These programs will benefit from assessing participants’ perceived importance of these behaviors, and from identifying the needs of unique groups, such as older persons and those pertaining to ethno-cultural groups. Show more

Keywords: Behavior, brain health, dementia, perceptions, prevention, risk-reduction

DOI: 10.3233/JAD-200780

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1011-1017, 2020

Authors: Reschke-Hernández, Alaine E. | Belfi, Amy M. | Guzmán-Vélez, Edmarie | Tranel, Daniel

Article Type: Research Article

Abstract: Background: Research has indicated that individuals with Alzheimer’s-type dementia (AD) can experience prolonged emotions, even when they cannot recall the eliciting event. Less is known about whether music can modify the emotional state of individuals with AD and whether emotions evoked by music linger in the absence of a declarative memory for the eliciting event. Objective: We examined the effects of participant-selected recorded music on self-reported feelings of emotion in individuals with AD, and whether these feelings persisted irrespective of declarative memory for the emotion-inducing stimuli. Methods: Twenty participants with AD and 19 healthy comparisons (HCs) …listened to two 4.5-minute blocks of self-selected music that aimed to induce either sadness or happiness. Participants reported their feelings at baseline and three times post-induction and completed recall and recognition tests for the music selections after each induction. Results: Participants with AD had impaired memory for music selections compared to HCs. Both groups reported elevated sadness and negative affect after listening to sad music and increased happiness and positive affect after listening to happy music, relative to baseline. Sad/negative and happy/positive emotions endured up to 20 minutes post-induction. Conclusion: Brief exposure to music can induce strong and lingering emotions in individuals with AD. These findings extend the intriguing phenomenon whereby lasting emotions can be prompted by stimuli that are not remembered declaratively. Our results underscore the utility of familiar music for inducing emotions in individuals with AD and may ultimately inform strategies for using music listening as a therapeutic tool with this population. Show more

Keywords: Alzheimer’s disease, dementia, feelings, emotion, memory, music

DOI: 10.3233/JAD-200889

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1019-1031, 2020

Authors: Juárez-Cedillo, Teresa | Gutiérrez-Gutiérrez, Lidia | Sánchez-Hurtado, Luis Alejandro | Martínez-Rodríguez, Nancy | Juarez-Cedillo, Enrique

Article Type: Research Article

Abstract: Background: Dementia is a persistent, progressive state of cognitive decline against which pharmacological intervention has a modest efficacy, reducing behavioral but not cognitive symptoms. Therefore, different non-pharmacological therapies have been developed; the most scientifically recognized are cognitive therapies that have improved cognitive function and daily life activities. Objective: To evaluate the effectiveness of a multicomponent cognitive stimulation therapy (SADEM) on cognitive and behavioral function and daily life activities in patients with mild stage dementia. Methods: Controlled clinical trial with pre- and post-intervention (12 months) and follow-up (24 months after) evaluations. Participants (67) diagnosed with mild dementia …were randomly assigned to intervention group (n  = 39) or control group (n  = 28). The intervention took place throughout one year and consisted of two weekly 90-minute sessions and one more a year after a monthly follow-up. Instruments were used to evaluate outcomes in cognitive, behavioral, and affective domains. Results: The results showed statistically significant differences, with improvement in the cognitive outcomes and the Dementia Index post-intervention (p  = 0.01). No progression of the disease was observed at the end of the study. Conclusion: The multicomponent intervention tested had positive effects on cognitive and behavioral functions and daily life activities in people with mild stage dementia, delaying progression for at least two years. Show more

Keywords: Cognitive stimulation therapy, dementia, functional cognition, multicomponent intervention, music therapy, SADEM

DOI: 10.3233/JAD-200574

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1033-1045, 2020

Authors: Lejko, Nena | Larabi, Daouia I. | Herrmann, Christoph S. | Aleman, André | Ćurčić-Blake, Branislava

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) is a stage between expected age-related cognitive decline and dementia. Dementias have been associated with changes in neural oscillations across the frequency spectrum, including the alpha range. Alpha is the most prominent rhythm in human EEG and is best detected during awake resting state (RS). Though several studies measured alpha power and synchronization in MCI, findings have not yet been integrated. Objective: To consolidate findings on power and synchronization of alpha oscillations across stages of cognitive decline. Methods: We included studies published until January 2020 that compared power or functional connectivity …between 1) people with MCI and cognitively healthy older adults (OA) or people with a neurodegenerative dementia, and 2) people with progressive and stable MCI. Random-effects meta-analyses were performed when enough data was available. Results: Sixty-eight studies were included in the review. Global RS alpha power was lower in AD than in MCI (ES = –0.30; 95% CI = –0.51, –0.10; k  = 6), and in MCI than in OA (ES = –1.49; 95% CI = –2.69, –0.29; k  = 5). However, the latter meta-analysis should be interpreted cautiously due to high heterogeneity. The review showed lower RS alpha power in progressive than in stable MCI, and lower task-related alpha reactivity in MCI than in OA. People with MCI had both lower and higher functional connectivity than OA. Publications lacked consistency in MCI diagnosis and EEG measures. Conclusion: Research indicates that RS alpha power decreases with increasing impairment, and could—combined with measures from other frequency bands—become a biomarker of early cognitive decline. Show more

Keywords: Alpha rhythm, brain waves, dementia, electroencephalography, mild cognitive impairment

DOI: 10.3233/JAD-200962

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1047-1088, 2020

Authors: Gkioka, Mara | Schneider, Julia | Kruse, Andreas | Tsolaki, Magda | Moraitou, Despina | Teichmann, Birgit

Article Type: Research Article

Abstract: Background: People with Dementia (PwD) are frequently admitted to hospital settings. The lack of proper dementia knowledge, poor communication skills, negative attitudes toward dementia, and lack of confidence affects the quality of care, thus development of dementia trainings has increased. Nevertheless, literature regarding the effectiveness of training implementation is limited. Objective: The aim of this narrative synthesis is to 1) identify the characteristics of training programs and 2) explore the effectiveness of these training programs in everyday clinical practice. Methods: A systematic search in PubMed, PsycINFO, CINAHL, and Cochrane was conducted, including qualitative and quantitative peer-reviewed …studies. Holton’s evaluation model with its three outcome levels (learning, individual performance, and organizational results) was adopted. 14 studies were included. Results: The synthesis of the results was divided into two parts: 1) to describe the characteristics and content of trainings 2) to evaluate the effectiveness of training programs according to the three outcome levels of Holton’s model, taking into consideration its construct domains: ability, motivation, and environment. Learning outcomes were assessed in all selected studies: 13 studies observed changes in individual performance, four studies reported changes within the organizational level, and only five showed sustainable changes over time. Conclusion: Person-centered care (PCC) approaches, interactive and varied teaching methods, supporting conditions like champions, action plans, and setting care policies, are all characteristics of effective trainings. Successful programs should be sustainable over time, demonstrating positive outcomes across the organization. Based on current findings, there is a lack of adequate evaluation with regard to training programs on the organizational level. Show more

Keywords: Alzheimer’s disease, education, health facilities, literature synthesis, personnel, workforce development

DOI: 10.3233/JAD-200741

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1089-1108, 2020

Authors: Fields, Taylor N. | Mueller, Kimberly D. | Koscik, Rebecca L. | Johnson, Sterling C. | Okonkwo, Ozioma C. | Litovsky, Ruth Y.

Article Type: Research Article

Abstract: Background: Growing evidence suggests hearing loss is a risk factor for mild cognitive impairment and dementia, but few studies have examined its relationship to sub-clinical cognitive outcomes. Objective: To investigate the effect of self-reported hearing loss on longitudinal cognitive function in a risk-enriched cohort of clinically-unimpaired, late middle-aged adults. Methods: 579 participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) were included. Hearing status was determined via self-reported history of diagnosed hearing loss. Each participant with self-reported hearing loss was age- and sex-matched to two participants who never reported hearing loss using nearest-neighbor matching. Linear mixed-effects …models were used to examine associations between self-reported hearing loss and age-related cognitive trajectories with covariates of sex, literacy, and ethnicity, person-level random intercepts and age-related slopes. Cognitive outcomes encompassed measures of speed and flexibility, visuospatial memory, and verbal fluency. Results: Participants with self-reported hearing loss exhibited significantly poorer performance on a speed and flexibility factor score and single test of psychomotor speed and executive function, relative to participants who never reported hearing loss. There was no association between self-reported hearing loss and visuospatial memory or verbal fluency. Longitudinally, self-reported hearing loss was associated with less rapid decline in speed and flexibility and no difference in rate of decline for any other cognitive measure. Conclusion: Self-reported hearing loss was associated with poorer speed and flexibility but not with accelerated decline in any domain studied, contrary to previous findings. Further studies involving behavioral auditory measures in this cohort would clarify the robustness of these findings. Show more

Keywords: Alzheimer’s disease, cognition, cognitive impairment, executive function, hearing, hearing loss, longitudinal studies

DOI: 10.3233/JAD-200701

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1109-1117, 2020

Authors: Liu, Kathy Y. | Costello, Harry | Reeves, Suzanne | Howard, Robert | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Agitation in Alzheimer’s disease (AD) has been hypothesized to be an expression of anxiety, but whether anxiety early in the course of dementia could be a risk factor for developing later agitation is unknown. Objective: We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the longitudinal relationship between anxiety and incident agitation in individuals with a diagnosis of AD at baseline or during follow-up. Methods: Longitudinal neuropsychiatric symptom data from AD individuals who were agitation-free at study baseline (N  = 272) were analyzed using mixed effects regression models to test the longitudinal relationship between …baseline and incident anxiety with incident agitation. Results: Anxiety at baseline was not associated with subsequent agitation, but there was a positive linear relationship between incident anxiety and agitation over the study duration. Baseline apathy and delusions were consistently associated with subsequent agitation and greater disease severity and illness duration also appeared to be risk factors for agitation. Conclusion: Our findings support the concept that anxiety and agitation are likely to be distinct rather than equivalent constructs in mild-moderate AD. Future longitudinal cohort studies are needed to replicate these findings and further characterize potential risk factors for agitation, such as apathy and delusions. Show more

Keywords: Agitation, Alzheimer’s disease, Alzheimer’s Disease Neuroimaging Initiative, anxiety, apathy, delusions

DOI: 10.3233/JAD-200516

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1119-1127, 2020

Authors: Tan, Meng-Shan | Yang, Yu-Xiang | Wang, Hui-Fu | Xu, Wei | Tan, Chen-Chen | Zuo, Chuan-Tao | Dong, Qiang | Tan, Lan | Yu, Jin-Tai | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. …All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42 , APOE ɛ 4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis. Show more

Keywords: Alzheimer’s disease, amyloid-β, APOE, biomarker, cerebrospinal fluid, Mini-Mental State Examination, PET, tau

DOI: 10.3233/JAD-200124

Citation: Journal of Alzheimer's Disease, vol. 78, no. 3, pp. 1129-1136, 2020