Journal of Alzheimer's Disease - Volume 78, issue 4

Authors: Zygouris, Stelios | Gkioka, Mara | Moraitou, Despina | Teichmann, Birgit | Tsiatsos, Thrasyvoulos | Papagiannopoulos, Sotirios | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: Despite the abundance of research on computerized dementia screening tests, the attitudes of hospital personnel toward this screening method have not been investigated. Objective: 1) To conduct a confirmatory factor analysis of the first part of a two-part questionnaire about computerized dementia screening. 2) To assess the attitudes of Greek nurses toward computerized dementia screening. 3) To assess barriers to future implementation of computerized dementia screening in the Greek healthcare system, as reported by nurses. Methods: 161 Greek nurses from two urban public general hospitals who participated in a dementia training program were recruited. They …were asked to complete a two-part questionnaire about computerized dementia screening. The first part of the questionnaire assesses attitudes toward dementia screening while the second part of the questionnaire assesses barriers to its implementation. Results: Confirmatory factor analysis on the first part of the questionnaire suggested a two-factor structure (feasibility/acceptability). The total score of all items loading on each factor was calculated. For feasibility, scores ranged between 10 and 25 (M = 19.38, SD = 3.80). For acceptability, scores ranged between 6 and 20 (M = 15.27, SD = 2.76). The main barriers to implementation were cost of equipment, insufficient training, lack of a plan for the integration of computerized screening tests in the daily routine of the hospital and time needed for staff training. Conclusion: The positive attitude of nurses supports the implementation of computerized dementia screening in public hospitals as long as identified barriers are addressed. Show more

Keywords: Attitude of health personnel, cognitive assessment screening instrument, dementia, geriatric nursing, hospitals, neurocognitive tests, questionnaire design, questionnaires, screening

DOI: 10.3233/JAD-200666

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1575-1583, 2020

Authors: Chen, Jen-Hau | Kuo, Tsung-Yu | Yu, Hwa-Lung | Wu, Charlene | Yeh, Su-Ling | Chiou, Jeng-Min | Chen, Ta-Fu | Chen, Yen-Ching

Article Type: Research Article

Abstract: Background: Previous studies have assessed limited cognitive domains with relatively short exposure to air pollutants, and studies in Asia are limited. Objective: This study aims to explore the association between long-term exposure to air pollutants and cognition in community-dwelling older adults. Methods: This four-year prospective cohort study recruited 605 older adults at baseline (2011–2013) and 360 participants remained at four-year follow-up. Global and domain-specific cognition were assessed biennially. Data on PM2.5 (particulate matter≤2.5μ m diameter, 2005–2015), PM10 (1993–2015), and nitrogen dioxide (NO2 , 1993–2015) were obtained from Taiwan Environmental Protection Administration (TEPA). Bayesian Maximum …Entropy was utilized to estimate the spatiotemporal distribution of levels of these pollutants. Results: Exposure to high-level PM2.5 (>29.98μ g/m3) was associated with an increased risk of global cognitive impairment (adjusted odds ratio = 4.56; β= –0.60). High-level PMcoarse exposure (>26.50μ g/m3 ) was associated with poor verbal fluency (β= –0.19). High-level PM10 exposure (>51.20μ g/m3 ) was associated with poor executive function (β= –0.24). Medium-level NO2 exposure (>28.62 ppb) was associated with better verbal fluency (β= 0.12). Co-exposure to high concentrations of PM2.5 , PMcoarse or PM10 and high concentration of NO2 were associated with poor verbal fluency (PM2.5 and NO2 : β= –0.17; PMcoarse and NO2 : β= –0.23; PM10 and NO2 : β= –0.21) and poor executive function (PM10 and NO2 : β= –0.16). These associations became more evident in women, apolipoprotein ɛ 4 non-carriers, and those with education > 12 years. Conclusion: Long-term exposure to PM2.5 (higher than TEPA guidelines), PM10 (lower than TEPA guidelines) or co-exposure to PMx and NO2 were associated with poor global, verbal fluency, and executive function over 4 years. Show more

Keywords: Air pollutants, cognitive impairment, cohort study, NO2 , older adults, PM2.5 , PM10 , PMcoarse

DOI: 10.3233/JAD-200614

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1585-1600, 2020

Authors: Richter, Nils | Bischof, Gérard N. | Dronse, Julian | Nellessen, Nils | Neumaier, Bernd | Langen, Karl-Josef | Drzezga, Alexander | Fink, Gereon R. | van Eimeren, Thilo | Kukolja, Juraj | Onur, Oezguer A.

Article Type: Research Article

Abstract: Background: To date, it remains unclear how amyloid plaques and neurofibrillary tangles are related to neural activation and, consequently, cognition in Alzheimer’s disease (AD). Recent findings indicate that tau accumulation may drive hippocampal hyperactivity in cognitively normal aging, but it remains to be elucidated how tau accumulation is related to neural activation in AD. Objective: To determine whether the association between tau accumulation and hippocampal hyperactivation persists in mild cognitive impairment (MCI) and mild dementia or if the two measures dissociate with disease progression, we investigated the relationship between local tau deposits and memory-related neural activation in MCI …and mild dementia due to AD. Methods: Fifteen patients with MCI or mild dementia due to AD underwent a neuropsychological assessment and performed an item memory task during functional magnetic resonance imaging. Cerebral tau accumulation was assessed using positron emission tomography and [18 F]-AV-1451. Results: Entorhinal, but not global tau accumulation, was highly correlated with hippocampal activation due to visual item memory encoding and predicted memory loss over time. Neural activation in the posterior cingulate cortex and the fusiform gyrus was not significantly correlated with tau accumulation. Conclusion: These findings extend previous observations in cognitively normal aging, demonstrating that entorhinal tau continues to be closely associated with hippocampal hyperactivity and memory performance in MCI and mild dementia due to AD. Furthermore, data suggest that this association is strongest in medial temporal lobe structures. In summary, our data provide novel insights into the relationship of tau accumulation to neural activation and memory in AD. Show more

Keywords: AV-1451, dementia, functional magnetic resonance imaging, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-200835

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1601-1614, 2020

Authors: Drenth, Hans | Zuidema, Sytse | Bautmans, Ivan | Marinelli, Lucio | Kleiner, Galit | Hobbelen, Hans

Article Type: Research Article

Abstract: Background: Paratonia is a dementia-induced motor abnormality. Although paratonia affects virtually all people with dementia, it is not well known among clinicians and researchers. Objective: The aim of this study was to perform a systematic review of the literature on the definition, pathogenesis, diagnosis, and intervention of paratonia as well as to propose a research agenda for paratonia. Methods: In this systematic review, the Embase, PubMed, CINAHL, and Cochrane CENTRAL databases were searched for articles published prior to December 2019. Two independent reviewers performed data extraction and assessed the risk of bias of the studies. The …following data were extracted: first author, year of publication, study design, study population, diagnosis, assessment, pathogenesis, therapy and interventions. Results: Thirty-five studies met the inclusion criteria and were included. Most studies included in the review mention clinical criteria for paratonia. Additionally, pathogenesis, method of assessment, diagnosis, and paratonia severity as are interventions to address paratonia are also discussed. Conclusion: This systematic review outlines what is currently known about paratonia, as well as discusses the preliminary research on the underlying mechanisms of paratonia. Although paratonia has obvious devastating impacts on health and quality of life, the amount of research to date has been limited. In the last decade, there appears to have been increased research on paratonia, which hopefully will increase the momentum to further advance the field. Show more

Keywords: Dementia, motor disorders, motor skills disorders, paratonia, systematic review

DOI: 10.3233/JAD-200691

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1615-1637, 2020

Authors: Tai, Hong | Hirano, Shigeki | Sakurai, Toru | Nakano, Yoshikazu | Ishikawa, Ai | Kojima, Kazuho | Li, Hongliang | Shimada, Hitoshi | Kashiwado, Koichi | Mukai, Hiroki | Horikoshi, Takuro | Sugiyama, Atsuhiko | Uno, Takashi | Kuwabara, Satoshi

Article Type: Research Article

Abstract: Background: Neuropsychological tests, structural neuroimaging, and functional neuroimaging are employed as diagnostic and monitoring biomarkers of patients with Alzheimer’s disease (AD) Objective: We aimed to elucidate the similarities and differences in neuropsychological tests and neuroimaging with the use of the Mini-Mental State Examination (MMSE), Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), structural magnetic resonance image (MRI), and perfusion single photon emission computed tomography (SPECT), and parametric image analyses to understand its role in AD. Methods: Clinically-diagnosed AD patients (n = 155) were scanned with three-dimensional T1-weighted MRI and N -isopropyl-p-[123 I] iodoamphetamine SPECT. Statistical parametric mapping 12 was …used for preprocessing images, statistical analyses, and voxel-based morphometry for gray matter volume analyses. Group comparison (AD versus healthy controls), multiple regression analyses with MMSE, ADAS-cog total score, and ADAS-cog subscores as variables, were performed. Results: The AD group showed bilateral hippocampal volume reduction and hypoperfusion in the bilateral temporo-parietal lobe and posterior midline structures. Worse MMSE and ADAS-cog total score were associated with bilateral temporo-parietal volume loss and hypoperfusion. MMSE, but not ADAS-cog, was associated with the posterior midline structures. The ADAS-cog subscores were associated with the temporal volume, while perfusion analyses were linked to the left temporo-parietal region with the language function and right analogous region with the constructional praxis subscore. Conclusion: MMSE and ADAS-cog are associated with temporo-parietal regions, both in volume and perfusion. The MMSE score is associated with posterior midline structures and linked to an abnormal diagnostic AD pattern. Perfusion image analyses better represents the cognitive function in AD patients Show more

Keywords: Alzheimer’s disease, alzheimer’s disease assessment scale, mini-mental state examination, regional cerebral blood flow, voxel-based morphometry

DOI: 10.3233/JAD-200676

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1639-1652, 2020

Authors: Gardener, Hannah | Caunca, Michelle | Dong, Chuanhui | Cheung, Ying Kuen | Rundek, Tatjana | Elkind, Mitchell S.V. | Wright, Clinton B. | Sacco, Ralph L.

Article Type: Research Article

Abstract: Background: Mid-life obesity is associated with cognitive impairment, though the relationship for late-life obesity is equivocal, and may depend on the anthropometric measure. Objective: We examined the relationship between adiposity and cognition across age categories, cognitive domains, and by measures of obesity in a multi-ethnic population-based cohort. Methods: The study included 1,179 Northern Manhattan Study participants with obesity measures at baseline (44% overweight, 30% obese), an initial neuropsychological assessment conducted within 7 years (mean age = 70), and a second cognitive assessment conducted on average 6 years later. Z-scores were derived for cognitive domains (episodic and semantic memory, …executive function, processing speed) and averaged to calculate global cognition. Body mass index (BMI) and waist:hip ratio (WHR) were examined in relation to cognitive performance and change over time, stratified by age, using linear regression models adjusting for vascular risk factors. Results: Among those age<65 years at baseline, greater WHR was associated with worse global cognitive performance at initial assessment and directly associated with decline in performance between assessments. The association with initial performance was strongest for non-Hispanic Whites (beta = –0.155/standard deviation, p  = 0.04), followed by non-Hispanic Black/African Americans (beta = –0.079/standard deviation, p  = 0.07), and Hispanics (beta = –0.055/standard deviation, p  = 0.03). The associations were most apparent for the domains of processing speed and executive function. There was no association for BMI among those <65 years. Among those age ≥65, there was no association for BMI or WHR with cognitive performance at initial assessment nor decline over time. Conclusion: Our results support the detrimental effect of mid-life rather than later life obesity, particularly abdominal adiposity, on cognitive impairment and decline. Show more

Keywords: Adiposity, cognition, cognitive dysfunction, epidemiology, obesity

DOI: 10.3233/JAD-201071

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1653-1660, 2020

Authors: Singh, Ayush | Allen, Dyron | Fracassi, Anna | Tumurbaatar, Batbayar | Natarajan, Chandramouli | Scaduto, Pietro | Woltjer, Randy | Kayed, Rakez | Limon, Agenor | Krishnan, Balaji | Taglialatela, Giulio

Article Type: Research Article

Abstract: Background: Certain individuals, here referred to as Non-Demented with Alzheimer Neuropathology (NDAN), do not show overt neurodegeneration (N- ) and remain cognitively intact despite the presence of plaques (A +) and tangles (T +) that would normally be consistent with fully symptomatic Alzheimer’s disease (AD). Objective: The existence of NDAN (A  + T+ N- ) subjects suggests that the human brain utilizes intrinsic mechanisms that can naturally evade cognitive decline normally associated with the symptomatic stages of AD (A  + T+ N+ ). Deciphering the underlying mechanisms would prove relevant to develop complementing therapeutics to prevent progression of AD-related cognitive …decline. Methods: Previously, we have reported that NDAN present with preserved neurogenesis and synaptic integrity paralleled by absence of amyloid oligomers at synapses. Using postmortem brain samples from age-matched control subjects, demented AD patients and NDAN individuals, we performed immunofluorescence, western blots, micro transplantation of synaptic membranes in Xenopus oocytes followed by twin electrode voltage clamp electrophysiology and fluorescence assisted single synaptosome-long term potentiation studies. Results: We report decreased tau oligomers at synapses in the brains of NDAN subjects. Furthermore, using novel approaches we report, for the first time, that such absence of tau oligomers at synapses is associated with synaptic functional integrity in NDAN subjects as compared to demented AD patients. Conclusion: Overall, these results give further credence to tau oligomers as primary actors of synaptic destruction underscoring cognitive demise in AD and support their targeting as a viable therapeutic strategy for AD and related tauopathies. Show more

Keywords: Alzheimer’s disease, cognitive reserve, electrophysiology, flow cytometry, immunofluorescence, synapses, synaptosomes, tauopathy, western blotting

DOI: 10.3233/JAD-200716

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1661-1678, 2020

Authors: Yang, Yu-Xiang | Kuo, Kevin | Li, Hong-Qi | Shen, Xue-Ning | Chen, Shi-Dong | Cui, Mei | Dong, Qiang | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: Several studies have shown risky behaviors and risk tolerance are associated with Alzheimer’s disease. However, the underlying causality remains unclear. Risky behavior and risk tolerance may induce the onset of Alzheimer’s disease, and/or vulnerability to Alzheimer’s disease may result in more risky behaviors. Objective: To examine bidirectional relationships between risky behavior, risk tolerance, and Alzheimer’s disease using Mendelian randomization method for assessing potential causal inference. Methods: This bidirectional two-sample Mendelian randomization study used independent genetic variants associated with risky behaviors and risk tolerance (n  = 370, 771– 939, 908), and Alzheimer’s disease (n  = 71, 880 – …37, 613) as genetic instruments from large meta-analyses of genome-wide association studies. Results: Our results support a strong protective casual effect of risk-taking tendency on AD (odds ratio [OR] = 0.79; 95% CI, 0.67– 0.94, p  = 0.007). There was weak statistically significant relationship between number of sexual partners and AD (OR = 0.50, 95% CI, 0.27– 0.93, p  = 0.04), and between family history of AD and automobile speeding propensity (OR = 1.018, 95% CI, 1.005 to 1.031; p  = 0.007). Contrary to expectations, there was no statistically significant causal effect of AD on risk-taking tendency (β =  0.015, 95% CI, – 0.005 to 0.04; p  = 0.14). Conclusion: Under Mendelian randomization assumptions, our results suggest a protective relationship between risk-taking tendency and the risk of AD. This finding may provide valuable insights into Alzheimer’s disease pathogenesis and the development of preventive strategies. Show more

Keywords: Alzheimer’s disease, causality, mendelian randomization analysis, risk behavior

DOI: 10.3233/JAD-200773

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1679-1687, 2020

Authors: Mehling, Wolf E. | Scott, Travis M. | Duffy, James | Whitmer, Rachel A. | Chesney, Margaret A. | Boscardin, W. John | Barnes, Deborah E.

Article Type: Research Article

Abstract: Background: Non-pharmacological therapies for persons with dementia (PWD) are needed. Objective: To develop and test the Paired Preventing Loss of Independence through Exercise (PLIÉ) program, an integrative group movement program for PWD and care partners (CPs). Methods: Participants were randomized to immediate or delayed start to Paired PLIÉ in community-based classes (1 hour, 2 days/week, 12 weeks, 3 home visits). Co-primary outcomes included standard measures of cognition, physical function,and quality of life (PWD) and caregiver burden (CPs) assessed by blinded assessors, analyzed using linear mixed models to calculate effect sizes for outcome changes during Paired PLIÉ, …controlling for randomization group. Anonymous satisfaction surveys included satisfaction ratings and thematic analysis of open-ended responses. Results: Thirty dyads enrolled, 24 (80%) completed. PWD (mean age 80; 55% female) experienced significant improvement in self-rated quality of life (Effect Size+0.23; p  = 0.016) when participating in Paired PLIÉ, while CPs experienced a non-significant increase in burden (–0.23, p  = 0.079). Changes in physical and cognitive function in PWD were not significant. All CPs returning the satisfaction survey (n  = 20) reported being moderately-to-highly satisfied with the program. Thematic analyses identified physical (e.g., sit-to-stand, more energy), emotional (enjoyment), and social benefits (peer-to-peer interaction) for PWD and CPs; challenges were primarily related to getting to the in-person classes. Conclusion: Paired PLIÉ is a promising integrative group movement program that warrants further study. It is feasible and may improve self-rated quality of life in PWD. Although CPs may experience increased burden due to logistical challenges, most reported high satisfaction and physical, emotional, and social benefits. Show more

Keywords: Alzheimer’s disease, caregiver, dementia, exercise, quality of life

DOI: 10.3233/JAD-200713

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1689-1706, 2020

Authors: Guarnieri, Biancamaria | Maestri, Michelangelo | Cucchiara, Federico | Lo Gerfo, Annalisa | Schirru, Alessandro | Arnaldi, Dario | Mattioli, Pietro | Nobili, Flavio | Lombardi, Gemma | Cerroni, Gianluigi | Bartoli, Antonella | Manni, Raffaele | Sinforiani, Elena | Terzaghi, Michele | Arena, Maria Grazia | Silvestri, Rosalia | La Morgia, Chiara | Di Perri, Maria Caterina | Franzoni, Ferdinando | Tognoni, Gloria | Mancuso, Michelangelo | Sorbi, Sandro | Bonuccelli, Ubaldo | Siciliano, Gabriele | Faraguna, Ugo | Bonanni, Enrica

Article Type: Research Article

Abstract: Background: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention. Objective: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities. Methods: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, …and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status. Results: Wake after sleep onset (WASO) was higher (p  < 0.001) and sleep efficiency (SE) lower (p  = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p  = 0.004). SE was lower in male AD compared to female AD (p  = 0.038) and SRI lower in male AD compared to male controls (p  = 0.008), male MCI (p  = 0.047), but also female AD subjects (p  = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p  = 0.009) in the overall population, controls (p  = 0.005), and AD subjects (p  = 0.034). The confusion-matrices showed good predictive power of actigraphic data. Conclusion: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications. Show more

Keywords: Alzheimer’s disease, circadian rhythms, confusion matrix, mild cognitive impairment, sex differences, sleep disturbances, sleep parameters, sleep regularity index, wearable activity tracker

DOI: 10.3233/JAD-200632

Citation: Journal of Alzheimer's Disease, vol. 78, no. 4, pp. 1707-1719, 2020