Journal of Alzheimer's Disease - Volume 60, issue 1

Authors: Nagata, Tomoyuki | Nakajima, Shinichiro | Shinagawa, Shunichiro | Plitman, Eric | Nakayama, Kazuhiko | Graff-Guerrero, Ariel | Mimura, Masaru

Article Type: Research Article

Abstract: Background/Objective: The aim of the present study was to investigate predictors of atypical antipsychotic (AAP) treatment continuation and response by week 8 in patients with Alzheimer’s disease (AD) who have psychotic/aggressive symptoms using the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) dataset. Methods: Clinical data was utilized from 421 AD outpatients with psychotic/aggressive symptoms who needed interventional treatment. Logistic regression analyses were performed to examine which baseline sociodemographic and clinical characteristics contributed to treatment ‘continuation’ and ‘response’, the latter of which was evaluated by the Clinical Global Impression of Change (CGI-C), Neuropsychiatric Inventory (NPI), and Brief Psychiatric …Scale (BPRS). Results: The treatment continuation rate was 48.7%, and CGI-C, NPI, and BPRS response rate by the last observation carried forward method were 42.7%, 48.6%, and 37.5%, respectively. No significant predictor was identified for treatment continuation in the Caucasian patients (n  = 331), while better treatment response was predicted by a lower Mini-Mental State Examination score, treatment with risperidone (versus olanzapine and quetiapine), history of diabetes mellitus, healthier physical status, and more severe initial psychotic symptoms. Conclusions: Comparatively high intolerability from AAPs in the short term was confirmed. We found that baseline clinical predictors to treatment response in Caucasian AD patients with psychotic/aggressive symptoms include treatment with risperidone (versus quetiapine and olanzapine), diabetes mellitus, global physical status, cognitive impairment, and psychotic symptoms. Going forward, these findings may help to determine treatment strategies or care plans. Show more

Keywords: Aggression, Alzheimer’s disease, atypical antipsychotic, neuropsychiatric symptom, psychosis

DOI: 10.3233/JAD-170412

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 263-272, 2017

Authors: Oikonomidi, Aikaterini | Tautvydaitė, Domilė | Gholamrezaee, Mehdi M. | Henry, Hugues | Bacher, Michael | Popp, Julius

Article Type: Research Article

Abstract: Background: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory protein playing a regulatory role in the immune response. First evidence from in vitro and animal studies suggests that MIF may be involved in the development of Alzheimer’s disease (AD) pathology. Objective: To address in older subjects (i) the relationships between AD pathology and MIF plasma and cerebrospinal fluid (CSF) levels; and (ii) to investigate whether increased MIF-related systemic and CNS inflammation is associated with clinical disease progression. Methods: CSF and plasma concentrations of MIF as well as biomarkers of amyloid, neuronal injury, and tau hyperphosphorylation …(CSF Aβ1–42 , tau, and ptau, respectively) were assessed in 97 subjects with MCI or mild dementia (cognitive impairment, CI) and 52 healthy volunteers with normal cognition. Clinical and neuropsychological evaluations were performed at inclusion and at follow up visits. Results: CSF MIF levels were higher in participants with CI with an AD CSF biomarker profile, but not in CI with a non-AD profile, compared to the healthy controls. Higher MIF CSF levels were associated with higher CSF tau and ptau and lower CSF Aβ1–42 after adjusting for potential confounders. In CI, MIF CSF independently predicted cognitive decline at a follow-up visit after controlling for potential confounders including CSF Aβ1–42 and tau levels. Conclusion: Our study provides evidence that MIF-related inflammation is related to amyloid pathology, tau hyperphosphorylation, and neuronal injury at the early clinical stages of AD. Higher MIF CSF levels are associated with accelerated cognitive decline in MCI and mild dementia. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, cognitive decline, macrophage migration inhibitory factor, neuroinflammation

DOI: 10.3233/JAD-170335

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 273-281, 2017

Authors: Koychev, Ivan | Gunn, Roger N. | Firouzian, Azadeh | Lawson, Jennifer | Zamboni, Giovanna | Ridha, Basil | Sahakian, Barbara J. | Rowe, James B. | Thomas, Alan | Rochester, Lynn | Ffytche, Dominic | Howard, Robert | Zetterberg, Henrik | MacKay, Clare | Lovestone, Simon | on behalf of the Deep and Frequent Phenotyping study team ()

Article Type: Research Article

Abstract: Background: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer’s disease (AD). Objective: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. Methods: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F ]AV45) and tau ([18F ]AV1451) ligands at baseline. Results: 22 participants took part in the …study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ. Conclusion: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker— the CSF total tau/Aβ ratio. Show more

Keywords: Alzheimer’s disease, amyloid beta-peptides, cerebrospinal fluid proteins, positron emission tomography, tau proteins

DOI: 10.3233/JAD-170129

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 283-293, 2017

Authors: Beheshti, Iman | Maikusa, Norihide | Daneshmand, Morteza | Matsuda, Hiroshi | Demirel, Hasan | Anbarjafari, Gholamreza | for the Japanese-Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: In this study, we investigated the early detection of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) conversion to AD through individual structural connectivity networks using structural magnetic resonance imaging (sMRI) data. In the proposed method, the cortical morphometry of individual gray matter images were used to construct structural connectivity networks. A statistical feature generation approach based on histogram-based feature generation procedure was proposed to represent a statistical-pattern of connectivity networks from a high-dimensional space into low-dimensional feature vectors. The proposed method was evaluated on numerous samples including 61 healthy controls (HC), 42 stable-MCI (sMCI), 45 progressive-MCI (pMCI), and 83 …AD subjects at the baseline from the J-ADNI data-set using support vector machine classifier. The proposed method yielded a classification accuracy of 84.17%, 70.38%, and 61.05% in identifying AD/HC, MCIs/HCs, and sMCI/pMCI, respectively. The experimental results show that the proposed method performed in a comparable way to alternative methods using MRI data. Show more

Keywords: Alzheimer’s disease, anatomical connectivity networks, feature extraction, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-161080

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 295-304, 2017

Authors: Nikitidou, Elisabeth | Khoonsari, Payam Emami | Shevchenko, Ganna | Ingelsson, Martin | Kultima, Kim | Erlandsson, Anna

Article Type: Research Article

Abstract: Extracellular vesicles (EVs), including exosomes and larger microvesicles, have been implicated to play a role in several conditions, including Alzheimer’s disease (AD). Since the EV content mirrors the intracellular environment, it could contribute with important information about ongoing pathological processes and may be a useful source for biomarkers, reflecting the disease progression. The aim of the present study was to analyze the protein content of EVs specifically released from a mixed co-culture of primary astrocytes, neurons, and oligodendrocytes treated with synthetic amyloid-β (Aβ42 ) protofibrils. The EV isolation was performed by ultracentrifugation and validated by transmission electron microscopy. Mass spectrometry …analysis of the EV content revealed a total of 807 unique proteins, of which five displayed altered levels in Aβ42 protofibril exposed cultures. The most prominent protein was apolipoprotein E (apoE), and by western blot analysis we could confirm a threefold increase of apoE in EVs from Aβ42 protofibril exposed cells, compared to unexposed cells. Moreover, immunoprecipitation studies demonstrated that apoE was primarily situated inside the EVs, whereas immunocytochemistry indicated that the EVs most likely derived from the astrocytes and the neurons in the culture. The identified Aβ-induced sorting of apoE into EVs from cultured neuroglial cells suggests a possible role for intercellular transfer of apoE in AD pathology and encourage future studies to fully elucidate the clinical relevance of this event. Show more

Keywords: Alzheimer’s disease, amyloid-beta peptide, apolipoprotein E, astrocytes, exosomes, extracellular vesicles, mass spectrometry, neurons, shedding microvesicles

DOI: 10.3233/JAD-170278

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 305-321, 2017

Authors: Toots, Annika | Littbrand, Håkan | Boström, Gustaf | Hörnsten, Carl | Holmberg, Henrik | Lundin-Olsson, Lillemor | Lindelöf, Nina | Nordström, Peter | Gustafson, Yngve | Rosendahl, Erik

Article Type: Research Article

Abstract: Background: Although physical exercise has been suggested to influence cognitive function, previous exercise studies show inconsistent results in people with dementia. Objectives: To investigate effects of exercise on cognitive function in people with dementia. Method: The Umeå Dementia and Exercise (UMDEX) study, a cluster-randomized controlled trial, was set in 16 nursing homes in Umeå, Sweden. One hundred-and-forty-one women and 45 men with dementia; mean age of 85 y and mean Mini-Mental State Examination (MMSE) score of 15, were randomized to a High-Intensity Functional Exercise program or a seated attention control activity. Blinded assessors measured global cognitive …function using the MMSE and the Alzheimer’s disease Assessment Scale – Cognitive subscale (ADAS-Cog), and executive function using Verbal fluency (VF) at baseline and 4 months (directly after intervention completion), and MMSE and VF at 7 months. Results: Linear mixed models showed no between-group effects in mean difference from baseline (95% confidence intervals, CI) at 4 months in MMSE (–0.27; 95% CI –1.4 to 0.87, p  = 0.644), ADAS-Cog (–1.04, 95% CI –4 to 1.92, p  = 0.491), or VF (–0.53, 95% CI –1.42 to 0.35, p  = 0.241) or at 7 months in MMSE (–1.15, 95% CI –2.32 to 0.03, p  = 0.056) or VF (–0.18, 95% CI –1.09 to 0.74, p  = 0.707). Conclusion: A 4-month, high-intensity functional exercise program had no superior effects on global cognition or executive function in people with dementia living in nursing homes when compared with an attention control activity. Show more

Keywords: Cognition, dementia, exercise, residential facilities

DOI: 10.3233/JAD-170014

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 323-332, 2017

Authors: Ienca, Marcello | Jotterand, Fabrice | Elger, Bernice | Caon, Maurizio | Scoccia Pappagallo, Alessandro | Kressig, Reto W. | Wangmo, Tenzin

Article Type: Other

DOI: 10.3233/JAD-179005

Citation: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 333-333, 2017