Journal of Alzheimer's Disease - Volume 70, issue 2

Authors: Pérez-Ros, Pilar | Cubero-Plazas, Laura | Mejías-Serrano, Trinidad | Cunha, Cristina | Martínez-Arnau, Francisco M.

Article Type: Research Article

Abstract: Background: The current trend in addressing symptoms of dementia comprises non-pharmacological strategies such as music interventions for the management and improvement of cognitive function, memory, agitation, depression, or anxiety. Objective: To determine the impact of a preferred music listening group intervention upon the functional, cognitive, and emotional dimensions in nursing home residents. Methods: A randomized intervention study was carried out. The study was conducted from June to August 2015, and involved a preferred music listening group intervention lasting 60 minutes, 5 days/week during 8 weeks. A total of 119 adults aged ≥65 years, with annual permanent …residence in the nursing home (Málaga, Spain) were included in the study. 47 (39.5%) subjects were randomized to the music group intervention. The nurses and physiotherapists were blinded to the assessments. Results: The sample had a mean age of 80.52 (SD7.44) years, with female predominance. The subjects presented dependency in Barthel, and cognitive impairment as determined by the MMSE. The Tinetti scores yielded fall risk and depression as evidenced by the Yesavage scale. The Cornell scores evidenced no depression in elderly people with dementia. Following the intervention, function improved significantly with a medium effect size, as did emotional state, with a large effect size. Cognitive function was seen to worsen in the control group, but remained stable in the intervention group, with a large effect size. Conclusions: A preferred music listening group intervention among elderly people in nursing homes is effective, resulting in improvements in functional and emotional condition. Show more

Keywords: Care activities, dementia, elderly people, music, nursing homes

DOI: 10.3233/JAD-190361

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 433-442, 2019

Authors: Baroni, Luciana | Bonetto, Chiara | Rizzo, Gianluca | Bertola, Caterina | Caberlotto, Livio | Bazzerla, Giorgio

Article Type: Research Article

Abstract: Background: Cognitive disorders in old age have a serious impact on the health and social aspects of patients and their families. Objective: The scope of this paper is to explore the role of cobalamin and folate that has been linked to cognitive decline, not only as a deficiency state depending on malnutrition, but also a determinant in cognitive impairment. Methods: A 6-year observational, retrospective study was conducted by collecting the routine blood analyses and cognitive screening scores of patients aged 60 years or older, followed at our Centre for the Diagnosis and Treatment of Cognitive Disorders. …Results: In a linear regression with a multi-vitamin model, higher folate concentrations were correlated with better cognitive performances through MMSE score, even after correction for sex, age, and years of education (beta = 0.144, p  = 0.001). Estimated MMSE marginal means for folate versus homocysteine showed that folate deficiency was associated with worse cognitive performances, with a more severe cognitive impairment when hyperhomocysteinemia was present. Conclusion: The assessment of B-vitamin status among elderly adults can contribute to an economic and practical approach to the prevention and management of cognitive decline. Future studies focused to define optimal vitamin status are warranted. Show more

Keywords: Aged, Alzheimer’s disease, cognitive dysfunction, dementia, folic acid, homocysteine, mini-mental state examination, vitamin B 12

DOI: 10.3233/JAD-190249

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 443-453, 2019

Authors: Dani, Melanie | Wood, Melanie | Mizoguchi, Ruth | Fan, Zhen | Edginton, Trudi | Hinz, Rainer | Win, Zarni | Brooks, David James | Edison, Paul

Article Type: Research Article

Abstract: Background: Amyloid plaque and tau-containing neurofibrillary tangles are important features of Alzheimer’s disease (AD). However, the relationship between these processes is still debated. Objective: We aimed to investigate local and distant relationships between tau and amyloid deposition in the cortex in mild cognitive impairment (MCI) and AD using PET imaging. Methods: Seventy-nine subjects (51 controls, 13 amyloid-positive MCI subjects, and 15 amyloid positive AD subjects) underwent MRI and 18 F-flutemetamol PET. All MCI/AD subjects and 8 healthy controls as well as 33 healthy control subjects from the ADNI dataset also had 18 F-AV1451 PET. Regional and …distant correlations were examined after sampling target-to-cerebellar ratio images. Biological parametric mapping was used to evaluate voxel level correlations locally. Results: We found multiple clusters of voxels with highly significant positive correlations throughout the association cortex in both MCI and AD subjects. Conclusion: The multiple clusters of positive correlations indicate that tau and amyloid may interact locally and be involved in disease progression. Our findings suggest that targeting both pathologies may be required. Show more

Keywords: Alzheimer’s disease, amyloid, mild cognitive impairment, PET, tau

DOI: 10.3233/JAD-181168

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 455-465, 2019

Authors: Liu, Yumei | Perdomo, Sophy J. | Ward, Jaimie | Vidoni, Eric D. | Sisante, Jason F. | Kirkendoll, Kiersten | Burns, Jeffrey M. | Billinger, Sandra A.

Article Type: Research Article

Abstract: Background: Vascular health is closely related to Alzheimer’s disease (AD). Vascular function measured by flow mediated dilation (FMD) or pulsatility index (PI) can be used as marker of peripheral and central vascular health but is poorly characterized in those at risk for AD. Objective: To assess the relationship of peripheral and central vascular function with amyloid-β (Aβ) and white matter lesion burden among cognitively normal older adults. Methods: We enrolled participants 65 years of age and older. Using Doppler ultrasound, we assessed brachial artery FMD, and middle cerebral artery (PI). Global Aβ burden, quantified using [18F] …Florbetapir PET imaging, and white matter lesion volume (WML) were used as measures of AD pathology and vascular brain injury. Results: After adjusting for age and cardiovascular risk factors, the data (n  = 83) showed a negative association between FMD and Aβ burden (β= –0.03, p  < 0.001). FMD at a cut-off of 4.45% had 88% specificity and 75% sensitivity to elevated Aβ (AUC = 0.86, 95% CI: 0.77–0.95). FMD was not related to WML volume (p  = 0.8), and PI was unrelated to Aβ burden or WML volume (0 > 0.4). Conclusions: Among cognitively normal older adults, blunted peripheral vascular function, as measured by brachial artery FMD, is associated with Aβ burden. These findings provide support for further exploration into the pathophysiological relationship of vascular health and AD risk as measured by Aβ. Show more

Keywords: Amyloid-β protein, pulsatile flow, transcranial doppler sonography, vascular endothelium

DOI: 10.3233/JAD-181268

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 467-475, 2019

Authors: Jun, Sungmin | Kim, Heeyoung | Kim, Bum Soo | Yoo, Bong-Goo | Lee, Won Gu | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: This study was designed to investigate factors that predict progression from amnestic mild cognitive impairment (aMCI) to probable Alzheimer’s disease (AD). Objective: We studied the usefulness of quantitative assessment of amyloid burden measured by Florbetapir PET scan. Methods: The study cohort consisted of aMCI participants older than 65 and those with available Florbetapir PET scan at diagnosis from the ADNI database (http://adni.loni.usc.edu ). To assess the prognostic impact of amyloid burden, a staging system based on the global SUVr of the PET scan was applied. We defined the stages as: stage I, negative amyloid scan; …stage II, positive amyloid in 1st tertile; stage III, positive amyloid in 2nd tertile; and stage IV, positive amyloid in 3rd tertile. Results: Of 250 eligible aMCI subjects (age 74.1±5.4, female n  = 105), 71 (28.4%) were diagnosed with probable AD within 3 years. Higher amyloid stages showed faster cognitive decline by Kaplan-Meier analysis. In multivariate Cox analysis, with stage I as a reference, the hazard ratio (HR) increased as the stage increased: stage II (HR, 4.509; p  = 0.015), stage III (HR, 7.616; p  = 0.001), and stage IV (HR, 9.421; p  < 0.001). Along with amyloid stage, ApoE ɛ 4 (HR, 1.943; p  = 0.031), score of CDR-SB (HR, 1.845; p  < 0.001) and ADAS 11 (HR, 1.144; p  < 0.001), and hippocampal volume (HR, 0.002; p  = 0.005) were also identified as predictors of dementia progression in aMCI subjects. Conclusions: Large amyloid burden measured from amyloid PET scan could be a predictor of faster cognitive decline in aMCI patients. Show more

Keywords: Alzheimer’s disease, amyloid, Florbetapir, mild cognitive impairment, positron emission tomography

DOI: 10.3233/JAD-190070

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 477-486, 2019

Authors: Kawarabayashi, Takeshi | Terakawa, Teruhiko | Takahashi, Atsushi | Hasegawa, Hisakazu | Narita, Sakiko | Sato, Kaoru | Nakamura, Takumi | Seino, Yusuke | Hirohata, Mie | Baba, Nobue | Ueda, Tetsuya | Harigaya, Yasuo | Kametani, Fuyuki | Maruyama, Nobuyuki | Ishimoto, Masao | St. George-Hyslop, Peter | Shoji, Mikio

Article Type: Research Article

Abstract:  Amyloid-β (Aβ) plays a central role in the pathogenesis of Alzheimer’s disease (AD). Because AD pathologies begin two decades before the onset of dementia, prevention of Aβ amyloidosis has been proposed as a mean to block the pathological cascade. Here, we generate a transgenic plant-based vaccine, a soybean storage protein containing Aβ4–10, named Aβ+, for oral Aβ immunization. One mg of Aβ+ or control protein (Aβ–) was administered to TgCRND8 mice once a week from 9 weeks up to 58 weeks. Aβ+ immunization raised both anti-Aβ antibodies and cellular immune responses. Spatial learning decline was prevented in the Aβ+ immunized …group in an extended reference memory version of Morris water maze test from 21 to 57 weeks. In Tris-buffered saline (TBS), sodium dodecyl sulfate (SDS), and formic acid (FA) serial extractions, all sets of Aβ species from Aβ monomer, low to high molecular weight Aβ oligomers, and Aβ smears had different solubility in TgCRND8 brains. Aβ oligomers decreased in TBS fractions, corresponding to an increase in high molecular weight Aβ oligomers in SDS extracts and Aβ smears in FA fraction of the Aβ+ treated group. There was significant inhibition of histological Aβ burden, especially in diffuse plaques, and suppression of microglial inflammation. Processing of amyloid-β protein precursor was not different between Aβ+ and Aβ– groups. No evidence of amyloid-related inflammatory angiopathy was observed. Thus, Aβ+ oral immunization could be a promising, cheap, and long-term safe disease-modifying therapy to prevent the pathological process in AD. Show more

Keywords: Alzheimer’s disease, Alzheimer vaccines, amyloid-β oligomers, plant, prevention, soybean, spatial memory

DOI: 10.3233/JAD-190023

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 487-503, 2019

Authors: Matsuoka, Teruyuki | Ismail, Zahinoor | Narumoto, Jin

Article Type: Research Article

Abstract: Background: Mild behavioral impairment (MBI) has been proposed as risk factor for dementia, and for some, an early manifestation of dementia. Objective: We examined the prevalence of MBI in the psychiatric outpatient clinic, and compared the incidence of dementia in MBI with that in other psychiatric diseases. Methods: Retrospective chart review was conducted in 2,853 consecutive outpatients over the age of 50. MBI was diagnosed according to the International Society to Advance Alzheimer’s Research and Treatment research diagnostic criteria. The incidence rate of dementia was examined in the patients who were followed up for at least …1 month. Kaplan-Meier survival analyses and Cox proportional hazards regression models were performed to compare the time to onset of dementia between MBI and other psychiatric diseases. Results: The prevalence of MBI was 3.5% and the incidence of dementia was 30.7 cases per 1000 person-years. The hazard ratio (HR) for dementia was higher for MBI than other psychiatric diseases (HR: 8.07, 95% confidence interval: 4.34–15.03, p  < 0.001). In MCI patients, the cumulative survival in MCI with affective dysregulation tended to be lower than that in MCI without (p  = 0.090). Conclusions: Psychiatric outpatients often meet MBI criteria. MBI, especially the affective dysregulation domain, increases the risk of dementia in this psychiatric outpatient population. Since late-onset psychiatric and behavioral symptoms may be prodromal symptoms of dementia in some, careful observation is needed, and psychiatric clinicians should keep prodromal dementia on their differential diagnosis when assessing those with new onset psychiatric symptomatology in older adults. Show more

Keywords: Dementia, depression, mild behavioral impairment, mild cognitive impairment, neuropsychiatric symptoms, sleep disorder, subjective cognitive decline

DOI: 10.3233/JAD-190278

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 505-513, 2019

Authors: Nakagawa, Yoshitaka | Funayama, Michitaka | Kato, Masahiro

Article Type: Research Article

Abstract: Logoclonia, which is the meaningless repetition of a syllable, particularly an end syllable of a word, has been described in patients with dementia for a century. The mechanisms behind logoclonia, however, have yet to be clarified. Among 914 patients with aphasia, five patients presented with logoclonia, all of whom were categorized as having logopenic variant PPA (lvPPA) during the initial stage of their illness and met the clinical criteria for diagnosis of probable Alzheimer’s disease. Cognitively, they were all severely impaired when they presented with logoclonia. During the progression from lvPPA to logoclonia in these patients, their naming abilities and …phonological output function deteriorated despite their retained speech fluency. Logoclonia might be a characteristic sign of advanced-stage lvPPA. Although logoclonia might be associated with perseveration, deterioration in naming abilities and phonological output function along with retained speech fluency might form the basis for the development of logoclonia. Show more

Keywords: Alzheimer’s disease, logoclonia, logopenic variant primary progressive aphasia, naming abilities, phonological output

DOI: 10.3233/JAD-190184

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 515-524, 2019

Authors: Martín-Maestro, Patricia | Gargini, Ricardo | García, Esther | Simón, Diana | Avila, Jesús | García-Escudero, Vega

Article Type: Research Article

Abstract: Mitochondrial alterations and oxidative stress are common features of Alzheimer’s disease brain and peripheral tissues. Moreover, mitochondrial recycling process by autophagy has been found altered in the sporadic form of the disease. However, the contribution of the main proteins involved in this pathology such as amyloid-β protein precursor (AβPP) and tau needs to be achieved. With this aim, human unmodified fibroblasts were transduced with lentivectors encoding APP and Tau and treated with CCCP to study the mitophagy process. Both AβPP and tau separately increased autophagy flux mainly by improving degradation phase. However, in the specific case of mitophagy, …labeling of mitochondria by PINK1 and PARK2 to be degraded by autophagy seemed reduced, which correlates with the long-term accumulation of mitochondria. Nevertheless, the combination of tau and AβPP was necessary to cause a mitophagy functional impairment reflected in the accumulation of depolarized mitochondria labeled by PINK1. The overexpression of Tau and APP recapitulates the mitophagy failure previously found in sporadic Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, amyloid-β protein precursor, mitochondria, mitophagy, tau

DOI: 10.3233/JAD-190086

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 525-540, 2019

Authors: Gustafson Jr., David H. | Gustafson Sr., David H. | Cody, Olivia J. | Chih, Ming-Yuan | Johnston, Darcie C. | Asthana, Sanjay

Article Type: Research Article

Abstract: Background: Family members absorb much of the care of dementia patients. The burden of care substantially impacts caregivers’ health, further straining our healthcare system. By 2050, the incidence of Alzheimer’s disease will more than double, increasing the numbers of family caregivers proportionally. Interventions that reduce their burden are needed to preserve their health as well as the viability of the healthcare system. Objective: This paper reports on the development and feasibility testing of a computer-based system intended to improve the lives of caregivers. D-CHESS (Dementia–Comprehensive Health Enhancement Support System) allows users to obtain information, communicate with other caregivers, …get help with care decisions, and share information with experts. Method: Thirty-one caregivers were randomly assigned to an intervention group receiving D-CHESS for 6 months or to a control group receiving a caregiving book. Surveys at 0, 2, 4, and 6 months evaluated caregiver burden, family conflict, satisfaction with decisions, social support, loneliness, anxiety, depression, and coping competence. Results: Survey findings suggest D-CHESS participants may perform better on measures of social support, anxiety, loneliness, and coping competence; the groups were equivalent on caregiver burden, decision satisfaction, and depression, and the control group reported less family conflict than the intervention. D-CHESS use data suggested enhancements to system design and content to increase awareness and use of various features. Conclusion: This study suggests that D-CHESS has potential to positively impact family caregivers and that the system merits further development and investigation with a full-scale clinical trial. Show more

Keywords: Alzheimer’s disease, computer-assisted decision making, dementia, family caregivers, health information technology, psychological stress, social support, technological innovations, technology, telemedicine

DOI: 10.3233/JAD-190052

Citation: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 541-552, 2019