Journal of Alzheimer's Disease - Volume 48, issue 1

Authors: Khalsa, Dharma Singh

Article Type: Review Article

Abstract: Although meditation is believed to be over five thousand years old, scientific research on it is in its infancy. Mitigating the extensive negative biochemical effects of stress is a superficially discussed target of Alzheimer’s disease (AD) prevention, yet may be critically important. This paper reviews lifestyle and stress as possible factors contributing to AD and meditation’s effects on cognition and well-being for reduction of neurodegeneration and prevention of AD. This review highlights Kirtan Kriya (KK), an easy, cost effective meditation technique requiring only 12 minutes a day, which has been successfully employed to improve memory in studies of people with …subjective cognitive decline, mild cognitive impairment, and highly stressed caregivers, all of whom are at increased risk for subsequent development of AD. KK has also been shown to improve sleep, decrease depression, reduce anxiety, down regulate inflammatory genes, upregulate immune system genes, improve insulin and glucose regulatory genes, and increase telomerase by 43%; the largest ever recorded. KK also improves psycho-spiritual well-being or spiritual fitness, important for maintenance of cognitive function and prevention of AD. KK is easy to learn and practice by aging individuals. It is the premise of this review that meditation in general, and KK specifically, along with other modalities such as dietary modification, physical exercise, mental stimulation, and socialization, may be beneficial as part of an AD prevention program. Show more

Keywords: Alzheimer’s disease, lifestyle, meditation, memory loss improvement, prevention, stress, psychospiritual well-being, reduction of risk factors

DOI: 10.3233/JAD-142766

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 1-12, 2015

Authors: Ashford, J. Wesson | Mahoney, Louise | Burkett, Tim

Article Type: Research Article

Abstract: Complementary and Integrative Medicine has been maturing as a field to support treatment for a variety of medical conditions. The approaches, including yoga, meditation, acupuncture, and dietary supplements, may assist patients in a variety of ways, though clear explanations for their mechanisms of action or measurements of their possible benefit are in most cases elusive. In this issue of the Journal of Alzheimer’s Disease, Khalsa examines the use of meditation as a stress-reduction technique and provides an argument that with a specific technique such stress reduction can be provided efficiently, with relatively little interference in daily activities, and might decrease …Alzheimer risk. This thorough review provides some evidence of physiological benefit of meditation to brain function. While any actual effect of meditation on Alzheimer pathophysiology is only conjectural, meditation has received considerable attention as a tool that may have positive psychological and medical benefits. Consequently, this review is welcome. What is less certain is whether the recommended meditation approach is of specific benefit for Alzheimer’s disease or any other condition above and beyond what might be provided by many other types of exercises (like singing in a chorus or doing cross-word puzzles) or physical activities (like swimming or yoga). Show more

Keywords: Meditation, Alzheimer’s disease, stress, psychological complementary medicine

DOI: 10.3233/JAD-150505

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 13-14, 2015

Authors: Siarkos, Kostas T. | Katirtzoglou, Everina A. | Politis, Antonios M.

Article Type: Review Article

Abstract: Depression in Alzheimer’s disease (dAD) is one of the most common behavioral and psychological symptoms of dementia, with devastating consequences not only for the affected individuals, but for caregivers as well. So far, pharmacological treatment of dAD has been based on the “monoamine hypothesis”. However, the reported moderate effects of approved antidepressants, as well as an increasing body of research evidence, suggest a more complex pathophysiologic mechanism. In the present paper, a systematic review of different treatments for dAD is presented that can inform the study of alternative neuropathological and neurobiological aspects of the disease aimed at the development of …more effective treatment targets. Show more

Keywords: Alzheimer’s disease, antidepressants, dementia, depression, treatment

DOI: 10.3233/JAD-148010

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 15-34, 2015

Authors: Shatenstein, Bryna | Barberger-Gateau, Pascale

Article Type: Research Article

Abstract: Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and …in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level. Show more

Keywords: Alzheimer’s disease, cognition, cognitive reserve, dementia, early intervention, education, life course, lifestyle, prevention, psychosocial factors, social policies

DOI: 10.3233/JAD-150256

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 35-53, 2015

Authors: Liu, Jia | Zhu, Ming-wei | Arzberger, Thomas | Wang, Lu-ning

Article Type: Short Communication

Abstract: A clinicopathological investigation was conducted on a case of an 89-year-old man with a 10-year history of progressive dementia who also suffered strokes, apathy, aphasia, dysarthria, weakness of both legs, and walking difficulties. At autopsy, we found an obvious atrophy of the frontal and temporal cortex. Lewy bodies (LBs) could be seen in brain stem, amygdala, and neocortex. Argyrophilic grains were observed in hippocampus, entorhinal cortex, neocortex, amygdala, and pons, as well as neurofibrillary tangles in the entorhinal cortex and hippocampus. The case presented here is a rare case of frontotemporal lobar degeneration with accumulation of argyrophilic grains and Lewy …bodies. Show more

Keywords: Argyrophilic grains, frontotemporal lobar degeneration, FTLD-tau, Lewy bodies

DOI: 10.3233/JAD-150225

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 55-58, 2015

Authors: Fins, Joseph J.

Article Type: Editorial

Abstract: Using critical methods drawn from clinical ethics and the humanities, the author considers the posthumously published The Reagan Diaries and suggests that they show evidence of an incipient dementia. In the wake of Berisha et al.’s analysis of presidential press conferences during the Reagan presidency, published in the Journal of Alzheimer’s Disease , that were suggestive of cognitive impairment, this reading of the president’s diaries merit additional scrutiny. Diary entries from Reagan’s second term differ from the first years of his presidency. They demonstrate less text, more laconic analysis, word finding difficulties, evidence of spatial confusion and suggestions of …disinhibition, all possibly early signs of cognitive impoverishment during the same period when the transcripts of his second term press conferences showed evidence suggestive of incipient Alzheimer’s Disease. While a definitive analysis of the president’s diaries can not be performed on the abridged published text, edited by the historian Douglas Brinkley, these findings are suggestive and warrant additional scrutiny. By melding quantitative approaches analyzing language use from Reagan’s presidential press conferences with methods from clinical ethics and literary criticism, future scholars can gain a fuller understanding of the president’s health while he was in office. Show more

DOI: 10.3233/JAD-150354

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 59-61, 2015

Authors: Söllvander, Sofia | Ekholm-Pettersson, Frida | Brundin, Rose-Marie | Westman, Gabriel | Kilander, Lena | Paulie, Staffan | Lannfelt, Lars | Sehlin, Dag

Article Type: Research Article

Abstract: The Alzheimer’s disease (AD)-related peptide amyloid-β (Aβ) has a propensity to aggregate into various assemblies including toxic soluble Aβ protofibrils. Several studies have reported the existence of anti-Aβ antibodies in humans. However, it is still debated whether levels of anti-Aβ antibodies are altered in AD patients compared to healthy individuals. Formation of immune complexes with plasma Aβ makes it difficult to reliably measure the concentration of circulating anti-Aβ antibodies with certain immunoassays, potentially leading to an underestimation. Here we have investigated anti-Aβ antibody production on a cellular level by measuring the amount of anti-Aβ antibody producing cells instead of the …plasma level of anti-Aβ antibodies. To our knowledge, this is the first time the anti-Aβ antibody response in plasma has been compared in AD patients and age-matched healthy individuals using the enzyme-linked immunospot (ELISpot) technique. Both AD patients and healthy individuals had low levels of B cells producing antibodies binding Aβ40 monomers, whereas the number of cells producing antibodies toward Aβ42 protofibrils was higher overall and significantly higher in AD compared to healthy controls. This study shows, by an alternative and reliable method, that there is a specific immune response to the toxic Aβ protofibrils, which is significantly increased in AD patients. Show more

Keywords: Amyloid-β, amyloid-β protofibrils, anti-amyloid-β antibodies, enzyme-linked immunospot assay

DOI: 10.3233/JAD-150236

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 63-72, 2015

Authors: Snir, Jonatan A. | Suchy, Mojmir | Lawrence, Keith St. | Hudson, Robert H.E. | Pasternak, Stephen H. | Bartha, Robert

Article Type: Research Article

Abstract: Background: Cathepsin D (CatD) is a lysosomal protease that is elevated early in Alzheimer’s disease (AD). We have previously developed a Targeted contrast agent (CA) to detect CatD activity in vivo , consisting of a magnetic resonance imaging/fluorescent moiety linked to a cell penetrating peptide (CPP) by means of a CatD cleavage site and have demonstrated its uptake in the brain of an AD mouse model. Objective: The purpose of this study was to characterize the in vivo retention of a near infra-red fluorescent dye labeled version of this CA. Methods: …Six adult C57Bl/6 wild-type mice and six adult 5XFAD transgenic AD mice were studied using a small animal imaging system at five and twelve months of age using our novel Targeted CA, or two different control CAs; a Non-Targeted (lacking the CatD cleavage site) and a Non-Penetrating (lacking the CPP). Following intravenous CA administration, the optical signal was recorded within the brain and uptake and washout curves were measured and fitted to a one-phase exponential decay curve. Results: In all wild-type and 5XFAD mice, the washout of the Targeted CA that included a CPP domain was significantly slower than the washout of the Non-Penetrating and Non-Targeted CA. Furthermore, the washout of the CatD Targeted CA was significantly slower in the 5XFAD mice compared to the age matched wild-type controls (p  <  0.05) at 5 and 12 months of age. Control CAs showed no differences in washout. Conclusions: The prolonged retention of the CatD targeted CA in 5XFAD mice suggests this agent may be useful for AD detection. Show more

Keywords: Alzheimer’s disease, Cathepsin D, molecular imaging, optical imaging, transgenic mice

DOI: 10.3233/JAD-150123

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 73-87, 2015

Authors: Zhang, Xiao-Fang | Zhao, Yan-Feng | Zhu, Shun-Wei | Huang, Wei-Jie | Luo, Yan | Chen, Qing-Ying | Ge, Li-Jun | Li, Run-Sheng | Wang, Jian-Fei | Sun, Mu | Xiao, Zhi-Cheng | Fan, Guo-Huang

Article Type: Research Article

Abstract: Truncation of tau protein is considered an early event in Alzheimer’s disease (AD) and is believed to play a major pathogenic role in sporadic AD. However, causative factors that trigger tau truncation in AD remain poorly understood. In the present study, we demonstrate that CXCL1 (C-X-C motif ligand 1), a specific ligand for the chemokine receptor CXCR2, induced cleavage of tau at ASP421 in a caspase-3-dependent manner in long-term but not short-term cultured neurons. The cleaved tau formed varicosities or bead-like structures along the neurites, an abnormal distribution of tau induced by CXCL1 that has not been observed previously. …CXCL1-induced activation of GSK3β and the subsequent phosphorylation of tau preceded and were required for caspase-3 activation and tau cleavage. Moreover, intrahippocampal microinjection of lentiviral CXCL1 induced tau cleavage in hippocampal neurons in aged (15–18 months of age) but not adult mice (5–10 months of age). Our data highlight a new role of CXCR2 in tau cleavage and suggest that targeting CXCR2 may offer therapeutic benefits to patients with AD and potentially other tauopathies. Show more

Keywords: Caspase-3, CXCL1, CXCR2, hippocampal neurons, tau cleavage

DOI: 10.3233/JAD-150041

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 89-104, 2015

Authors: Kristofikova, Zdena | Ricny, Jan | Vyhnalek, Martin | Hort, Jakub | Laczo, Jan | Sirova, Jana | Klaschka, Jan | Ripova, Daniela

Article Type: Research Article

Abstract: Background: Overexpression of the mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10, which is also known as the intracellular amyloid-β peptide (Aβ) binding protein) is observed in cortical or hippocampal regions of patients with Alzheimer’s disease (AD). It appears that 17β-HSD10 may play a role in the pathogenesis of AD. Objective: We investigated the possibility that levels of 17β-HSD10 in cerebrospinal fluid could be a prospective biomarker of AD. Methods: We estimated the enzyme levels in 161 people (15 non-demented controls, 52 people with mild cognitive impairment (MCI), 35 people with probable AD, or …59 people with other types of dementia) and compared them with those of Aβ1 - 42 , tau, and phospho-tau. Results: We found significantly higher levels of 17β-HSD10 in people with MCI due to AD (to 109.9% ), with AD (to 120.0% ), or with other types of dementia (to 110.9% ) when compared to the control group. The sensitivity of the new biomarker to AD was 80.0% , and the specificity was 73.3% (compared to controls) or 52.5–59.1% (compared to other types of dementia). Results of multiple linear regression and of correlation analysis revealed AD-mediated changes in links between 17β-HSD10 and Mini Mental State Examination score. Conclusion: It seems that changes in 17β-HSD10 start many years before symptom onset, analogous to those in Aβ1 - 42 , tau, or phospho-tau and that the levels are a relatively highly sensitive but unfortunately less specific biomarker of AD. A role of 17β-HSD10 overexpression in AD is discussed. Show more

Keywords: 17β-HSD10, Alzheimer’s disease, amyloid-β peptides, biomarker, cerebrospinal fluid

DOI: 10.3233/JAD-142898

Citation: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 105-114, 2015