Journal of Alzheimer's Disease - Volume 39, issue 2

Authors: Mandal, Pravat K. | Ritchie, Karen | Fodale, Vincenzo

Article Type: Editorial

DOI: 10.3233/JAD-131487

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 223-225, 2014

Authors: Molinuevo, José L. | Casado-Naranjo, Ignacio

Article Type: Short Communication

Abstract: Epidemiological and clinical studies suggest that dementia patients aged ≥ 85 years are biologically different from those aged 65–84. This study aimed to assess whether patients (>85 years) have a distinct sociodemographic and clinical profile. Older patients had lower educational achievements, different carer relationships, and were more likely to take memantine/concomitant treatments and be institutionalized. Differences were observed with respect to concomitant disease/other risk factors (depression, dyslipidemia, cardiovascular disease, hypertension). Oldest patients had greater impairment (more severe Global Deterioration Scale stage, lower Mini-Mental State Examination scores). Greater concomitant drug use and younger carers associated with older patients suggest higher management …and social costs. Show more

Keywords: Age, Alzheimer's disease, dementia, sociodemographic, treatment

DOI: 10.3233/JAD-131433

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 227-232, 2014

Authors: Nafar, Firoozeh | Mearow, Karen M.

Article Type: Short Communication

Abstract: Dietary supplementation has been studied as an approach to ameliorating deficits associated with aging and neurodegeneration. We undertook this pilot study to investigate the effects of coconut oil supplementation directly on cortical neurons treated with amyloid-β (Aβ) peptide in vitro. Our results indicate that neuron survival in cultures co-treated with coconut oil and Aβ is rescued compared to cultures exposed only to Aβ. Coconut oil co-treatment also attenuates Aβ-induced mitochondrial alterations. The results of this pilot study provide a basis for further investigation of the effects of coconut oil, or its constituents, on neuronal survival focusing on mechanisms that may …be involved. Show more

Keywords: Coconut oil, Amyloid, cortical neurons

DOI: 10.3233/JAD-131436

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 233-237, 2014

Authors: Xu, Shujun | Liu, Guilan | Bao, Xiaoming | Wu, Jie | Li, Shaomin | Zheng, Bangxu | Anwyl, Roger | Wang, Qinwen

Article Type: Research Article

Abstract: Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain to be fully elucidated. In this study, living-cell image, immunocytochemistry, and electrophysiology were used to examine the effects of soluble amyloid-β protein (Aβ) oligomers and rosiglitazone on the synapse formation, plasticity, and mitochondrial distribution in cultured neurons. Incubation of hippocampal cultures with amyloid-β (Aβ)42 oligomers (0.5 μM) for 3 h significantly decreased dendritic filopodium and synapse density. Pretreatment with rosiglitazone (0.5–5 μM) for 24 h prevented the Aβ42 -induced loss of dendritic filopodium and synapse in a dose-dependent manner. However, neither Aβ42 …oligomer nor rosiglitazone has a significant effect on the velocity and length of dendritic filopodia. Electrophysiological recording showed that acute exposure of slices with 0.5 μM Aβ42 oligomers impaired hippocampal long-term potentiation (LTP). Pre-incubation of hippocampal slices with rosiglitazone significantly attenuated the Aβ42 -induced LTP deficit, which depended on rosiglitazone concentrations (1–5 μM) and pretreatment period (1–5 h). The beneficial effects of rosiglitazone were abolished by the peroxisome proliferator-activated receptor gamma (PPARγ) specific antagonist, GW9662. Moreover, the mitochondrial numbers in the dendrite and spine were decreased by Aβ42 oligomers, which can be prevented by rosiglitazone. In conclusion, our data suggested that rosiglitazone prevents Aβ42 oligomers-induced impairment via increasing mitochondrial numbers in the dendrite and spine, improving synapse formation and plasticity. This process is most likely through the PPARγ-dependent pathway and in concentration and time dependent manners. The study provides novel insights into the mechanisms for the protective effects of rosiglitzone on AD. Show more

Keywords: Alzheimer's disease, amyloid-β, mitochondria, PPARγ, rosiglitazone, synapse formation, synapse plasticity

DOI: 10.3233/JAD-130680

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 239-251, 2014

Authors: Kiko, Takehiro | Nakagawa, Kiyotaka | Tsuduki, Tsuyoshi | Furukawa, Katsutoshi | Arai, Hiroyuki | Miyazawa, Teruo

Article Type: Research Article

Abstract: The development of Alzheimer's disease (AD) biomarkers remains an unmet challenge, and new approaches that can improve current AD biomarker strategies are needed. Recent reports suggested that microRNA (miRNA) profiling of biological fluids has emerged as a diagnostic tool for several pathologic conditions. In this study, we measured six candidate miRNAs (miR-9, miR-29a, miR-29b, miR-34a, miR-125b, and miR-146a) in plasma and cerebrospinal fluid (CSF) of AD and normal subjects by using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to evaluate their potential usability as AD biomarkers. The qRT-PCR results showed that plasma miR-34a and miR-146a levels, and CSF miR-34a, miR-125b, and …miR-146a levels in AD patients were significantly lower than in control subjects. On the other hand, CSF miR-29a and miR-29b levels were significantly higher than in control subjects. Our results provide a possibility that miRNAs detected in plasma and CSF can serve as biomarkers for AD. Show more

Keywords: Alzheimer's disease, cerebrospinal fluid, miRNA, plasma

DOI: 10.3233/JAD-130932

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 253-259, 2014

Authors: Lu, Po H. | Lee, Grace J. | Shapira, Jill | Jimenez, Elvira | Mather, Michelle J. | Thompson, Paul M. | Bartzokis, George | Mendez, Mario F.

Article Type: Research Article

Abstract: Background: White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer’s disease (AD). Objective: Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. Methods: We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable …late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. Results: Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. Conclusions: The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group. Show more

Keywords: Alzheimer's disease, behavioral variant, diffusion tensor imaging, early onset, frontotemporal dementia, magnetic resonance imaging, myelin, white matter

DOI: 10.3233/JAD-131481

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 261-269, 2014

Authors: Singh, Balwinder | Parsaik, Ajay K. | Mielke, Michelle M. | Erwin, Patricia J. | Knopman, David S. | Petersen, Ronald C. | Roberts, Rosebud O.

Article Type: Research Article

Abstract: Background/Objective: To conduct a systematic review of all studies to determine whether there is an association between the Mediterranean diet (MeDi) and cognitive impairment. Methods: We conducted a comprehensive search of the major databases and hand-searched proceedings of major neurology, psychiatry, and dementia conferences through November 2012. Prospective cohort studies examining the MeDi with longitudinal follow-up of at least 1 year and reporting cognitive outcomes (mild cognitive impairment [MCI] or Alzheimer’s disease [AD]) were included. The effect size was estimated as hazard-ratio (HR) with 95% confidence intervals (CIs) using the random-effects model. Heterogeneity was assessed using Cochran’s Q-test …and I2 -statistic. Results: Out of the 664 studies screened, five studies met eligibility criteria. Higher adherence to the MeDi was associated with reduced risk of MCI and AD. The subjects in the highest MeDi tertile had 33% less risk (adjusted HR = 0.67; 95% CI, 0.55–0.81; p < 0.0001) of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI (HR = 0.73; 95% CI, 0.56–0.96; p = 0.02) and AD (HR = 0.64; 95% CI, 0.46–0.89; p = 0.007). There was no significant heterogeneity in the analyses. Conclusions: While the overall number of studies is small, pooled results suggest that a higher adherence to the MeDi is associated with a reduced risk of developing MCI and AD, and a reduced risk of progressing from MCI to AD. Further prospective-cohort studies with longer follow-up and randomized controlled trials are warranted to consolidate the evidence. Systematic review registration number: PROSPERO 2013: CRD42013003868. Show more

Keywords: Alzheimer's disease, Mediterranean diet, meta-analysis, mild cognitive impairment, systematic review

DOI: 10.3233/JAD-130830

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 271-282, 2014

Authors: Solfrizzi, Vincenzo | Panza, Francesco

Article Type: Research Article

Abstract: Higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline, although the Mediterranean diet (MeDi) combines several foods, micronutrients, and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. The findings from prospective studies and very recent systematic reviews and meta-analyses suggested that adherence to the MeDi fulfilling the whole-diet approach may affect not only the risk of Alzheimer's disease, but also of predementia syndromes and their progression to overt dementia. However, some concerns exist regarding how these instruments have been developed for measuring adherence to the MeDi, suggesting a better qualitative and quantitative …selection of the individual dietary components and/or food groups to improve their reliability. Show more

Keywords: Alzheimer's disease, Mediterranean diet, meta-analysis, mild cognitive impairment, systematic review

DOI: 10.3233/JAD-130831

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 283-286, 2014

Authors: Schmitz, Xavier | Bier, Nathalie | Joubert, Sven | Lejeune, Caroline | Salmon, Eric | Rouleau, Isabelle | Meulemans, Thierry

Article Type: Research Article

Abstract: Identifying the conditions favoring new procedural skill learning in Alzheimer's disease (AD) could be important for patients' autonomy. It has been suggested that error elimination is beneficial during skill learning, but no study has explored the advantage of this method in sequential learning situations. In this study, we examined the acquisition of a 6-element perceptual-motor sequence by AD patients and healthy older adults (control group). We compared the impact of two preliminary sequence learning conditions (Errorless versus Errorful) on Serial Reaction Time performance at two different points in the learning process. A significant difference in reaction times for the learned …sequence and a new sequence was observed in both conditions in healthy older participants; in AD patients, the difference was significant only in the errorless condition. The learning effect was greater in the errorless than the errorful condition in both groups. However, while the errorless advantage was found at two different times in the learning process in the AD group, in the control group this advantage was observed only at the halfway point. These results support the hypothesis that errorless learning allows for faster automation of a procedure than errorful learning in both AD and healthy older subjects. Show more

Keywords: Alzheimer's disease, perceptual motor performance, reaction time, rehabilitation, serial learning

DOI: 10.3233/JAD-130887

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 287-300, 2014

Authors: Yu, Dezhi | LaPointe, Nichole E. | Guzman, Elmer | Pessino, Veronica | Wilson, Leslie | Feinstein, Stuart C. | Valentine, Megan T.

Article Type: Research Article

Abstract: We tested the hypothesis that mutant tau proteins that cause neurodegeneration and dementia differentially alter kinesin translocation along microtubules (MTs) relative to normal tau in vitro. We employed complementary in vitro motility assays using purified recombinant kinesin, purified recombinant tau, and purified bovine brain α:β tubulin to isolate interactions among these components without any contribution by cellular regulatory mechanisms. We found that kinesin translocates slower along MTs assembled by any of three independent tau mutants (4-repeat P301L tau, 4-repeat ΔN296 tau, and 4-repeat R406W tau) relative to its translocation rate along MTs assembled by normal, 4-repeat wild type (WT) tau. …Moreover, the R406W mutation exhibited isoform specific effects; while kinesin translocation along 4-repeat R406W tau assembled MTs is slower than along MTs assembled by 4-repeat WT tau, the R406W mutation had no effect in the 3-repeat tau context. These data provide strong support for the notion that aberrant modulation of kinesin translocation is a component of tau-mediated neuronal cell death and dementia. Finally, we showed that assembling MTs with taxol before coating them with mutant tau obscured effects of the mutant tau that were readily apparent using more physiologically relevant MTs assembled with tau alone, raising important issues regarding the use of taxol as an experimental reagent and novel insights into therapeutic mechanisms of taxol action. Show more

Keywords: Axonal transport, corticobasal degeneration, frontotemporal dementia with parkinsonism-17, kinesin, microtubules, motility, progressive supranuclear palsy, tau

DOI: 10.3233/JAD-131274

Citation: Journal of Alzheimer's Disease, vol. 39, no. 2, pp. 301-314, 2014