Journal of Alzheimer's Disease - Volume 64, issue 4

Authors: Pandareesh, Mirazkar D. | Chauhan, Ved | Chauhan, Abha

Article Type: Research Article

Abstract: Our previous study has shown beneficial effects of walnuts on memory and learning skills in transgenic mouse model of Alzheimer’s disease (AD-tg). To understand underlying mechanism, we studied here whether walnuts can reduce oxidative stress in AD. From 4 months of age, experimental AD-tg mice were fed diets containing 6% (T6) or 9% walnuts (T9) (equivalent to 1 or 1.5 oz, of walnuts per day in humans) for 5, 10, or 15 months. The control groups, i.e., AD-tg (T0) and wild-type (Wt) mice, were fed diets without walnuts. Free radicals, i.e., reactive oxygen species (ROS), lipid peroxidation, protein oxidation, and …antioxidant enzymes were assessed in these mice at different ages. AD-tg mice on control diet (T0) showed significant age-dependent increase in ROS levels, lipid peroxidation, and protein oxidation coupled with impaired activities of antioxidant enzymes [superoxide dismutase, catalase, and glutathione peroxidase] compared to Wt mice. Oxidative stress was significantly reduced in AD-tg mice on diets with walnuts (T6, T9), as evidenced by decreased levels of ROS, lipid peroxidation, and protein oxidation, as well as by enhanced activities of antioxidant enzymes compared to T0 mice. Long-term supplementation with walnuts for 10 or 15 months was more effective in reducing oxidative stress in AD-tg mice. Our findings indicate that walnuts can reduce oxidative stress, not only by scavenging free radicals, but also by protecting antioxidant status, thus leading to reduced oxidative damage to lipids and proteins in AD. Therefore, by reducing oxidative stress, a walnut-enriched diet may help reduce the risk or delay the onset and progression of AD. Show more

Keywords: Alzheimer’s disease, antioxidants, catalase, glutathione, lipid peroxidation, liver, oxidative stress, protein oxidation, reactive oxygen species, superoxide dismutase, walnuts

DOI: 10.3233/JAD-180361

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1295-1305, 2018

Authors: Abner, Erin L. | Neltner, Janna H. | Jicha, Gregory A. | Patel, Ela | Anderson, Sonya L. | Wilcock, Donna M. | Van Eldik, Linda J. | Nelson, Peter T.

Article Type: Research Article

Abstract: Data from a large autopsy series were analyzed to address questions pertinent to primary age-related tauopathy (PART) and Alzheimer’s disease (AD): what factors are associated with increased severity of neurofibrillary degeneration in brains that lack neuritic amyloid plaques?; is there an association between Apolipoprotein E (APOE ) alleles and PART pathologic severity independent of amyloid-β (Aβ ) deposits?; and, how do the stains used to detect plaques and tangles impact the experimental results? Neuropathologic data were evaluated from elderly research volunteers whose brain autopsies were performed at University of Kentucky Alzheimer’s Disease Center (UK-ADC; N = 145 subjects). …All of the included subjects’ brains lacked neuritic amyloid plaques according to the CERAD diagnostic criteria and the average final MMSE score before death was 26.8±4.6 stdev. The study incorporated evaluation of tissue with both silver histochemical stains and immunohistochemical stains to compare results; the immunohistochemical stains (Aβ and phospho-tau) were scanned and quantified using digital pathologic methods. Immunohistochemical stains provided important advantages over histochemical stains due to sensitivity and detectability via digital methods. When AD-type pathology was in its presumed earliest phases, neocortical parenchymal Aβ deposits were associated with increased medial temporal lobe neurofibrillary tangles. The observation supports the NIA-AA consensus recommendation for neuropathologic diagnoses, because even these “diffuse” Aβ deposits signal that AD pathobiologic mechanisms are occurring. Further, the data were most compatible with the hypothesis that the APOE ɛ 4 allele exerts its effect(s) via driving Aβ deposition, i.e., an “upstream” influence, rather than being associated directly with Aβ – independent PART pathology. Show more

Keywords: Aging, amyloid-β, Genie, hippocampus, MAPT, neuropathology, oldest-old, ScanScope, SNAP

DOI: 10.3233/JAD-180514

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1307-1324, 2018

Authors: Kent, Brianne A. | Strittmatter, Stephen M. | Nygaard, Haakon B.

Article Type: Research Article

Abstract: Background: Sleep disturbances have long been associated with Alzheimer’s disease (AD), and there is a growing interest in how these disturbances might impact AD pathophysiology. Despite this growing interest, surprisingly little is known about how sleep architecture and the broader neuronal network are affected in widely used transgenic mouse models of AD. Objective: We analyzed sleep and electroencephalography (EEG) power in three transgenic mouse models of AD, using identical and commercially available hardware and analytical software. The goal was to assess the suitability of these mouse lines to model sleep and the broader neuronal network dysfunction measured by …EEG in AD. Methods: Tg2576, APP/PS1, and 3xTgAD transgenic AD mice were studied using in vivo EEG recordings for sleep/wake time and power spectral analysis. Results: Both the APP/PS1 model at 8– 10 months and the Tg2576 model at 12 months of age exhibited stage-dependent decreases in theta and delta power, and shifts in the power spectra toward higher frequencies. Stage-dependent power spectral analyses showed no changes in the 3xTgAD model at 18 months of age. The percentage of time spent awake, in non-rapid eye movement sleep (NREM), or in rapid-eye-movement sleep (REM) was not different between genotypes in any of the transgenic lines. Conclusion: Our findings are consistent with data from several other transgenic AD models as well as certain studies in patients with mild cognitive impairment. Further studies will be needed to better understand the correlation between EEG spectra and AD pathophysiology, both in AD models and the human condition. Show more

Keywords: Alzheimer’s disease, dementia, EEG, sleep, transgenic mice

DOI: 10.3233/JAD-180260

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1325-1336, 2018

Authors: Jones, Susan May | Killett, Anne | Mioshi, Eneida

Article Type: Research Article

Abstract: Background: Dementia Cafés are community support groups which provide post-diagnostic support for families affected by dementia. However, little is known about the characteristics of caregivers who attend Cafés. Objectives: To describe the demographic and psychosocial characteristics of caregivers who attend Dementia Cafés, and to identify which of those factors may influence the likelihood of family caregivers attending Dementia Cafés. Methods: A cross-sectional study on caregivers (n = 80; July 2016– July 2017). Resilience (Brief Resilient Coping Scale), Subjective Wellbeing (Personal Wellbeing Index), and Social Support (MOS-Social Support Survey) were measured. Café attendees and non-attendees were …compared in regards to demographic characteristics (Chi-Square tests), resilience, subjective wellbeing and social support (independent t -tests). Bivariate and multivariate regression analyses were run to detect associations between predictor variables and café attendance. Results: Caregivers who attended Cafés reported higher resilience (OR: 1.26; 95% CI 1.10–1.45; p = 0.001) and subjective wellbeing (OR: 1.63; 95% CI 1.24–2.142; p = 0.001 ); no significant difference in social support was detected. Female caregivers were more likely to attend a Café (OR: 3.23; 95% CI 1.14–9.10; p = 0.03). However, only higher subjective wellbeing (OR: 1.63; 95% CI 1.10–24.2; p = 0.02) and fewer years formal education (OR: 4.99; 95% CI 1.12–21.36; p = 0.03) predicted attendance at a café. Conclusion: Dementia Cafés may bring about benefits in resilience and subjective wellbeing, or may be best suited to those with higher resilience and wellbeing. Cafes are not being accessed by all caregiver groups. Alternative models of post-diagnostic support should be considered to increase equity of care. Show more

Keywords: Caregiver, dementia, psychosocial intervention, resilience, social support, subjective wellbeing

DOI: 10.3233/JAD-180377

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1337-1345, 2018

Authors: Lyu, Jihui | Zhang, Jingnan | Mu, Haiyan | Li, Wenjie | Champ, Mei | Xiong, Qian | Gao, Tian | Xie, Lijuan | Jin, Weiye | Yang, Wan | Cui, Mengnan | Gao, Maolong | Li, Mo

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia, affecting millions of older people worldwide. However, pharmacological therapies have not achieved desirable clinical efficacy in the past decades. Non-pharmacological therapies have been receiving increased attention to treat dementia in recent years. Objective: This study explores the effects of music therapy on cognitive function and mental wellbeing of patients with AD. Methods: A total number of 298 AD patients with mild, moderate, or severe dementia participated in the study. The participants with each grade of severity were randomly divided into three groups, which were a …singing group, a lyric reading group, and a control group. These three groups received different interventions for three months. All participants underwent a series of tests on cognitive functions, neuropsychological symptoms, and activities of daily living at baseline, three months, and six months. Results: The analysis shows that music therapy is more effective for improving verbal fluency and for alleviating the psychiatric symptoms and caregiver distress than lyrics reading in patients with AD. Stratified analysis shows that music therapy is effective for enhancing memory and language ability in patients with mild AD and reducing the psychiatric symptoms and caregiver distress in patients with moderate or severe AD. However, no significant effect was found for activities of daily living in patients with mild, moderate, or severe AD. Conclusion: This study suggests that music therapy is effective in enhancing cognitive function and mental wellbeing and can be recommended as an alternative approach to manage AD associated symptoms. Show more

Keywords: Dementia, language, memory, music therapy

DOI: 10.3233/JAD-180183

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1347-1358, 2018

Authors: Musaeus, Christian Sandøe | Engedal, Knut | Høgh, Peter | Jelic, Vesna | Mørup, Morten | Naik, Mala | Oeksengaard, Anne-Rita | Snaedal, Jon | Wahlund, Lars-Olof | Waldemar, Gunhild | Andersen, Birgitte Bo

Article Type: Research Article

Abstract: Background: Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimer’s disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood. Objective: To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level. Methods: Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic …memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition. Results: At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed. Conclusion: Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone. Show more

Keywords: Alzheimer’s disease, dementia, diagnostic, EEG, mild cognitive impairment, power

DOI: 10.3233/JAD-180300

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1359-1371, 2018