Journal of Alzheimer's Disease - Volume 59, issue 4

Authors: Evgen’ev, Michail B. | Krasnov, George S. | Nesterova, Inna V. | Garbuz, David G. | Karpov, Vadim L. | Morozov, Alexey V. | Snezhkina, Anastasiya V. | Samokhin, Alexander N. | Sergeev, Alexander | Kulikov, Alexei M. | Bobkova, Natalia V.

Article Type: Research Article

Abstract: Heat shock protein 70, encoded by the HSPA1A gene in humans, is a key component of the machinery that protects neuronal cells from various stress conditions and whose production significantly declines during the course of aging and as a result of several neurodegenerative diseases. Herein, we investigated whether sub-chronic intranasal administration of exogenous Hsp70 (eHsp70) exerts a neuroprotective effect on the temporal cortex and areas of the hippocampus in transgenic 5XFAD mice, a model of Alzheimer’s disease. The quantitative analysis of neuronal pathologies in the compared groups, transgenic (Tg) versus non-transgenic (nTg), revealed high level of abnormalities in the brains …of transgenic mice. Treatment with human recombinant Hsp70 had profound rejuvenation effect on both neuronal morphology and functional state in the temporal cortex and hippocampal regions in transgenic mice. Hsp70 administration had a smaller, but still significant, effect on the functional state of neurons in non-transgenic mice as well. Using deep sequencing, we identified multiple differentially expressed genes (DEGs) in the hippocampus of transgenic and non-transgenic mice. Furthermore, this analysis demonstrated that eHsp70 administration strongly modulates the spectrum of DEGs in transgenic animals, reverting to a pattern similar to that observed in non-transgenic age-matched mice, which included upregulation of genes responsible for amine transport, transmission of nerve impulses and other pathways that are impaired in 5XFAD mice. Overall, our data indicate that Hsp70 treatment may be an effective therapeutic against old age diseases of the Alzheimer’s type. Show more

Keywords: 5XFAD mice, hippocampus, neuronal pathology, recombinant Hsp70, transcriptome

DOI: 10.3233/JAD-170398

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1415-1426, 2017

Authors: Seelye, Adriana | Mattek, Nora | Sharma, Nicole | Witter IV, Phelps | Brenner, Ariella | Wild, Katherine | Dodge, Hiroko | Kaye, Jeffrey

Article Type: Research Article

Abstract: Background: Driving is a key functional activity for many older adults, and changes in routine driving may be associated with emerging cognitive decline due to early neurodegenerative disease. Current methods for assessing driving such as self-report are inadequate for identifying and monitoring subtle changes in driving patterns that may be the earliest signals of functional change in developing mild cognitive impairment (MCI). Objective: This proof of concept study aimed to establish the feasibility of continuous driving monitoring in a sample of cognitively normal and MCI older adults for an average of 206 days using an unobtrusive driving …sensor and demonstrate that derived sensor-based driving metrics could effectively discriminate between MCI and cognitively intact groups. Methods: Novel objective driving measures derived from 6 months of routine driving monitoring were examined in older adults with intact cognition (n  = 21) and MCI (n  = 7) who were enrolled in the Oregon Center for Aging and Technology (ORCATECH) longitudinal assessment program. Results: Unobtrusive continuous monitoring of older adults’ routine driving using a driving sensor was feasible and well accepted. MCI participants drove fewer miles and spent less time on the highway per day than cognitively intact participants. MCI drivers showed less day-to-day fluctuations in their driving habits than cognitively intact drivers. Conclusion: Sensor-based driving measures are objective, unobtrusive, and can be assessed every time a person drives his or her vehicle to identify clinically meaningful changes in daily driving. This novel methodology has the potential to be useful for the early detection and monitoring of changes in daily functioning within individuals. Show more

Keywords: Aging, cognitive decline, mild neurocognitive disorder, technology

DOI: 10.3233/JAD-170116

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1427-1437, 2017

Authors: Defrancesco, Michaela | Marksteiner, Josef | Kemmler, Georg | Fleischhacker, Walter Wolfgang | Blasko, Imrich | Deisenhammer, Eberhard A.

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer’s type (DAT). Objectives: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT. Methods: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively. Depression was assessed using the Geriatric Depression Scale (GDS). Potential predictors of conversion from MCI to DAT …were analyzed by logistic regression analyses and additional survival-analytic methods. Results: Of the 260 patients (mean age 71.5±7.7 years), 83 (32%) converted to DAT within a mean follow-up time of 3.2±2.2 years and estimated one-year conversion rate of 10.1%. The univariate analysis showed with few exceptions (gender, use of antidepressants, low GDS score) group differences at baseline in patients converted to DAT compared to stable MCI patients. Logistic regression analysis as well as survival analysis revealed moderate to severe depression together with higher age and specific cognitive deficits as predictors of conversion from MCI to DAT. Conclusion: Our results support the predictive value of different neuropsychological measures on the progression of DAT. In addition, we found a strong negative influence of depression on conversion to DAT in MCI patients. These results emphasize the importance of assessing depressive symptoms in the early stages of DAT when evaluating the conversion from MCI to DAT. Show more

Keywords: Alzheimer’s disease, depression, mild cognitive impairment, risk factors

DOI: 10.3233/JAD-161135

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1439-1448, 2017

Authors: Hong, Honghai | Li, Yang | Su, Baochang

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD. However, those potential biomarkers are not validated in an AD mouse model. In the current study, we found that …circulating miR-125b, miR-9, and miR-191-5p are downregulated, and miR-28-3p is upregulated in an APP/PS1 transgenic mouse model of AD. Furthermore, the correlation analysis shows a positive correlation between the expression of miR-125b and cognitive function of the APP/PS1 transgenic mouse. Moreover, we also determined that the level of serum miR-125b, miR-9, and miR-191-5p were reversed in EGCG-treated APP/PS1 transgenic mouse models. Finally, the expression of miR-125b was significantly downregulated in EGCG-treated SH-SY5Y cells. Show more

Keywords: APP/PS1 transgenic mouse, Alzheimer’s disease, EGCG, miR-125b

DOI: 10.3233/JAD-170156

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1449-1458, 2017

Authors: Sindi, Shireen | Ngandu, Tiia | Hovatta, Iiris | Kåreholt, Ingemar | Antikainen, Riitta | Hänninen, Tuomo | Levälahti, Esko | Laatikainen, Tiina | Lindström, Jaana | Paajanen, Teemu | Peltonen, Markku | Khalsa, Dharma Singh | Wolozin, Benjamin | Strandberg, Timo | Tuomilehto, Jaakko | Soininen, Hilkka | Kivipelto, Miia | Solomon, Alina | for the FINGER study group

Article Type: Research Article

Abstract: Leukocyte telomere length (LTL) is a biomarker of aging, and it is associated with lifestyle. It is currently unknown whether LTL is associated with the response to lifestyle interventions. The goal is to assess whether baseline LTL modified the cognitive benefits of a 2-year multidomain lifestyle intervention (exploratory analyses). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a 2-year randomized controlled trial including 1,260 people at risk of cognitive decline, aged 60–77 years identified from the general population. Participants were randomly assigned to the lifestyle intervention (diet, exercise, cognitive training, and vascular risk management) and control (general health …advice) groups. Primary outcome was change in cognition (comprehensive neuropsychological test battery). Secondary outcomes were changes in cognitive domains: memory, executive functioning, and processing speed. 775 participants (392 control, 383 intervention) had baseline LTL (peripheral blood DNA). Mixed effects regression models with maximum likelihood estimation were used to analyze change in cognition as a function of randomization group, time, baseline LTL, and their interaction. Intervention and control groups did not significantly differ at baseline. Shorter LTL was related to less healthy baseline lifestyle. Intervention benefits on executive functioning were more pronounced among those with shorter baseline LTL (p -value for interaction was 0.010 adjusted for age and sex, and 0.007 additionally adjusted for baseline lifestyle factors). The FINGER intervention cognitive benefits were more pronounced with shorter baseline LTL, particularly for executive functioning, indicating that the multidomain lifestyle intervention was especially beneficial among higher-risk individuals. Show more

Keywords: Cognition, dementia, lifestyle, multidomain intervention, telomere length

DOI: 10.3233/JAD-170123

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1459-1470, 2017

Article Type: Other

Citation: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1471-1485, 2017