Journal of Alzheimer's Disease - Volume 52, issue 1

Authors: Ye, Qing | Bai, Feng | Zhang, Zhijun

Article Type: Review Article

Abstract: Background: Considerable evidence has been reported for the comorbidity between late-life depression (LLD) and Alzheimer’s disease (AD), both of which are very common in the general elderly population and represent a large burden on the health of the elderly. The pathophysiological mechanisms underlying the link between LLD and AD are poorly understood. Because both LLD and AD can be heritable and are influenced by multiple risk genes, shared genetic risk factors between LLD and AD may exist. Objective: The objective is to review the existing evidence for genetic risk factors that are common to LLD and AD …and to outline the biological substrates proposed to mediate this association. Methods: A literature review was performed. Results: Genetic polymorphisms of brain-derived neurotrophic factor, apolipoprotein E, interleukin 1-beta, and methylenetetrahydrofolate reductase have been demonstrated to confer increased risk to both LLD and AD by studies examining either LLD or AD patients. These results contribute to the understanding of pathophysiological mechanisms that are common to both of these disorders, including deficits in nerve growth factors, inflammatory changes, and dysregulation mechanisms involving lipoprotein and folate. Other conflicting results have also been reviewed, and few studies have investigated the effects of the described polymorphisms on both LLD and AD. Conclusion: The findings suggest that common genetic pathways may underlie LLD and AD comorbidity. Studies to evaluate the genetic relationship between LLD and AD may provide insights into the molecular mechanisms that trigger disease progression as the population ages. Show more

Keywords: Alzheimer’s disease, apolipoprotein E, brain-derived neurotrophic factor, interleukin 1-beta, late-life depression, methylenetetrahydrofolate reductase, single nucleotide polymorphism

DOI: 10.3233/JAD-151129

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 1-15, 2016

Authors: Lingler, Jennifer H. | Butters, Meryl A. | Gentry, Amanda L. | Hu, Lu | Hunsaker, Amanda E. | Klunk, William E. | Mattos, Meghan K. | Parker, Lisa A. | Roberts, J. Scott | Schulz, Richard

Article Type: Review Article

Abstract: The increased use of PET amyloid imaging in clinical research has sparked numerous concerns about whether and how to return such research test results to study participants. Chief among these is the question of how best to disclose amyloid imaging research results to individuals who have cognitive symptoms that could impede comprehension of the information conveyed. We systematically developed and evaluated informational materials for use in pre-test counseling and post-test disclosures of amyloid imaging research results in mild cognitive impairment (MCI). Using simulated sessions, persons with MCI and their family care partners (N  = 10 dyads) received fictitious but realistic information …regarding brain amyloid status, followed by an explanation of how results impact Alzheimer’s disease risk. Satisfaction surveys, comprehension assessments, and focus group data were analyzed to evaluate the materials developed. The majority of persons with MCI and their care partners comprehended and were highly satisfied with the information presented. Focus group data reinforced findings of high satisfaction and included 6 recommendations for practice: 1) offer pre-test counseling, 2) use clear graphics, 3) review participants’ own brain images during disclosures, 4) offer take-home materials, 5) call participants post-disclosure to address emerging questions, and 6) communicate seamlessly with primary care providers. Further analysis of focus group data revealed that participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one’s amyloid status as valuable and empowering. Show more

Keywords: Communication, counseling, mild cognitive impairment, positron emission tomography, research ethics

DOI: 10.3233/JAD-150985

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 17-24, 2016

Authors: Gómez-Tortosa, Estrella | Prieto-Jurczynska, Cristina | Serrano, Soledad | Franco-Macías, Emilio | Olivié, Laura | Gallego, Jesús | Guerrero-López, Rosa | Trujillo-Tiebas, María José | Ayuso, Carmen | García Ruiz, Pedro | Pérez-Pérez, Julián | Sainz, María José

Article Type: Short Communication

Abstract: For diagnostic purposes, we screened for the C9ORF72 mutation in a) 162 FTLD cases, and b) 145 cases with other diagnoses but with some frontotemporal features or manifestations previously reported in C9 carriers. Ten cases (onset 50 to 75 years) harbored the expansion: seven had FTLD syndromes (4.3% of total, 11% of familial cases), and three (2%) had a different diagnosis. All positive cases had family history of dementia, psychiatric disease, or ALS, but only 20% of families with mixed FTLD/ALS phenotypes carried the expansion. Language impairment was the most common symptom, followed by behavioral changes, memory deficits, and …parkinsonism. C9ORF72 mutation has a low frequency in our dementia series and very diverse clinical manifestations. Show more

Keywords: C9ORF72 gene, frontotemporal dementia, hexanucleotide expansion

DOI: 10.3233/JAD-150922

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 25-31, 2016

Authors: Sanders, Chelsea | Behrens, Stephanie | Schwartz, Sarah | Wengreen, Heidi | Corcoran, Chris D. | Lyketsos, Constantine G. | Tschanz, JoAnn T.

Article Type: Research Article

Abstract: Nutritional status may be a modifiable factor in the progression of dementia. We examined the association of nutritional status and rate of cognitive and functional decline in a U.S. population-based sample. Study design was an observational longitudinal study with annual follow-ups up to 6 years of 292 persons with dementia (72% Alzheimer’s disease, 56% female) in Cache County, UT using the Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-sb), and modified Mini Nutritional Assessment (mMNA). mMNA scores declined by approximately 0.50 points/year, suggesting increasing risk for malnutrition. Lower mMNA score predicted faster rate of decline on the …MMSE at earlier follow-up times, but slower decline at later follow-up times, whereas higher mMNA scores had the opposite pattern (mMNA by time β= 0.22, p  = 0.017; mMNA by time2 β= –0.04, p  = 0.04). Lower mMNA score was associated with greater impairment on the CDR-sb over the course of dementia (β= 0.35, p  <  0.001). Assessment of malnutrition may be useful in predicting rates of progression in dementia and may provide a target for clinical intervention. Show more

Keywords: Cognitive symptoms, dementia, disease progression, malnutrition, nutrition assessment

DOI: 10.3233/JAD-150528

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 33-42, 2016

Authors: Tan, Chen-Chen | Wan, Yu | Tan, Meng-Shan | Zhang, Wei | Wang, Zi-Xuan | Sun, Fu-Rong | Miao, Dan | Tan, Lan | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: Both Alzheimer’s disease (AD) and frontotemporal dementia (FTD) are a class of neurodegenerative diseases. Strong similarities in cerebrospinal fluid biomarker, imaging markers, and disease progression profiles suggest that some or most of the pathophysiology is shared between AD and FTD. A recent large genome-wide association study reported several single nucleotide polymorphisms (SNPs) at the RAB38, RAB38/CTSC, HLA-DRA/HLA-DRB5 , and BTNL2 in association with FTD. Objective: To explore whether these SNPs are associated with AD risk. Methods: We conducted a case-control study to investigate the association of FTD-associated loci in 2338 Han Chinese subjects. …Results: We observed significant differences in genotype distributions of rs302668 (pc  = 0.025), rs9268877 (pc  = 0.025), rs9268856 (p  <  0.001), and rs1980493 (pc  = 0.045) between cases and controls. The SNPs rs16913634 for RAB38/CTSC was unrelated to LOAD risk (p  = 0.088). Conclusion: The SNPs rs302668 in RAB38, rs9268877 and rs9268856 polymorphism in HLA-DRA/HLA-DRB5, and rs1980493 polymorphism in BTNL2 might play a role in the susceptibility to late-onset AD in the Han Chinese population. Show more

Keywords: Alzheimer’s disease, association study, frontotemporal dementia, polymorphism

DOI: 10.3233/JAD-151073

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 43-50, 2016

Authors: Lelental, Natalia | Brandner, Sebastian | Kofanova, Olga | Blennow, Kaj | Zetterberg, Henrik | Andreasson, Ulf | Engelborghs, Sebastiaan | Mroczko, Barbara | Gabryelewicz, Tomasz | Teunissen, Charlotte | Mollenhauer, Brit | Parnetti, Lucilla | Chiasserini, Davide | Molinuevo, Jose Luis | Perret-Liaudet, Armand | Verbeek, Marcel M. | Andreasen, Niels | Brosseron, Frederic | Bahl, Justyna M.C. | Herukka, Sanna-Kaisa | Hausner, Lucrezia | Frölich, Lutz | Labonte, Anne | Poirier, Judes | Miller, Anne-Marie | Zilka, Norbert | Kovacech, Branislav | Urbani, Andrea | Suardi, Silvia | Oliveira, Catarina | Baldeiras, Ines | Dubois, Bruno | Rot, Uros | Lehmann, Sylvain | Skinningsrud, Anders | Betsou, Fay | Wiltfang, Jens | Gkatzima, Olymbia | Winblad, Bengt | Buchfelder, Michael | Kornhuber, Johannes | Lewczuk, Piotr

Article Type: Research Article

Abstract: Background: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples. Objective: To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers. Methods: Three matrices were validated in this study: (A) human pooled CSF, (B) Aβ peptides spiked into human prediluted plasma, and (C) Aβ peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were …tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study. Results: NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at – 80°C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects. Conclusion: Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, laboratory diagnostics, quality control, tau

DOI: 10.3233/JAD-150883

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 51-64, 2016

Authors: Palmeri, Agostino | Mammana, Leonardo | Tropea, Maria Rosaria | Gulisano, Walter | Puzzo, Daniela

Article Type: Research Article

Abstract: Rhodiola Rosea (R. Rosea ) is a plant used in traditional popular medicine to enhance cognition and physical performance. R. Rosea medicinal properties have been related to its capability to act as an adaptogen, i.e., a substance able to increase the organism’s resistance to a variety of chemical, biological, and physical stressors in a non-specific way. These adaptogen properties have been mainly attributed to the glycoside salidroside, one of the bioactive compounds present in the standardized extracts of R. Rosea . Here, we aimed to investigate whether a single dose of salidroside is able to affect memory and emotional …behavior in wild type adult mice. We performed fear conditioning to assess cued and contextual memory, elevated plus maze and open field to evaluate anxiety, and tail suspension test to evaluate depression. Our results showed that a single i.p. administration of salidroside was able to enhance fear memory and exerted an anxiolytic and antidepressant effect. These data confirmed the adaptogenic effect of R. Rosea bioactive compounds in animal models and suggest that salidroside might represent an interesting pharmacological tool to ameliorate cognition and counteract mood disorders. Show more

Keywords: Adaptogen, anxiety, depression, memory, Rhodiola rosea, salidroside

DOI: 10.3233/JAD-151159

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 65-75, 2016

Authors: Allison, Samantha L. | Fagan, Anne M. | Morris, John C. | Head, Denise

Article Type: Research Article

Abstract: Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer’s disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n  = 42), clinically normal with preclinical AD (n  = 13), and early-stage symptomatic AD (n  = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD …was associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. Show more

Keywords: Aging, allocentric, amyloid, caudate nucleus, egocentric, hippocampus

DOI: 10.3233/JAD-150855

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 77-90, 2016

Authors: Yoon, Bora | Yang, Dong Won | Hong, Yun Jeong | Choi, Seong Hye | Park, Sun Ah | Park, Hee Kyung | Kim, Yong Duk | Shim, Yong S.

Article Type: Research Article

Abstract: Background & Objective: Depression frequently combines with dementia, including early-onset Alzheimer’s disease (EOAD). We investigated differences in prevalence and characteristics of depressive symptoms according to dementia severity in EOAD patients. Methods: The 15-item Korean version of the Geriatric Depression Scale (GDS-15) was administered to 412 EOAD patients. Factor analysis was used to assess GDS-15 factor structure. We subdivided participants into three groups by disease severity, then compared the frequencies and scores of individual GDS-15 items and performed logistic regression analysis to assess associations between depressive symptoms and EOAD stage. Results: Factor analysis yielded three factor …categories: 1) “hopelessness and ominousness” (symptoms no. 6, 8, 12, 14, 15); 2) “unhappiness and dissatisfaction” (no. 1, 3, 5, 7, 11); and 3) “monotony and lack of energy” (no. 2, 4, 9, 10, 13). Factor 2 depressive symptoms (no. 1, 5, 11) were less common in moderate EOAD. The risk of Factor 1 symptoms: no. 12 (OR, 2.04; 95% CI, 1.19–3.50; p  = 0.010) and 14 (OR, 1.84; 95% CI, 1.07–3.16; p  = 0.028) was higher in mild than very mild EOAD. The risk of Factor 2 symptoms: no. 9 (OR, 2.69; 95% CI, 1.08–6.71; p  = 0.033) and 13 (OR, 2.12; 95% CI, 1.02–4.40; p  = 0.043) was higher in moderate than mild EOAD. Conclusion: We confirmed that depressive symptoms differ according to EOAD severity. When assessing depressive symptoms related to dementia progression, we recommend focusing on “hopelessness and ominousness” in very mild EOAD and “unhappiness and dissatisfaction” in mild EOAD. Show more

Keywords: Alzheimer’s disease, depression, disease progression, early-onset, geriatric depression scale, prediction

DOI: 10.3233/JAD-150703

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 91-99, 2016

Authors: Zhang, Ximeng | Cai, Xiaoying | Shi, Xiaolei | Zheng, Zhenyang | Zhang, Aiwu | Guo, Junliang | Fang, Yannan

Article Type: Research Article

Abstract: Cognitive dysfunction has been shown to be associated with many risk factors, such as smoking, diabetes, and body mass index. Chronic obstructive pulmonary disease (COPD), a common disease within the elderly population, has also been found to be related to cognitive decline. However, whether COPD is a risk factor of cognitive dysfunction is not well established. The purpose of this meta-analysis is to investigate the role COPD plays in cognitive dysfunction. PubMed, Cochrane library and Web of Science databases were searched. Three cohort studies and eleven cross-sectional studies were found to be eligible. According to our results, COPD patients had …a higher risk of cognitive dysfunction than controls (OR [odds ratio]: 1.72; 95% CI, 1.12–2.65; p  = 0.01). The exacerbation of COPD was strongly correlated with cognitive decline. COPD patients performed worse than controls on the Mini– Mental State Examination test, but the results were not statistically significant (OR: –0.79; 95% CI, [–1.78, 0.19]; p  = 0.11). Thus, more attention should be given to the occurrence of cognitive decline in COPD patients. The prevention and control of COPD exacerbation are critical. Show more

Keywords: Chronic obstructive pulmonary disease, cognition, dementia, meta-analysis

DOI: 10.3233/JAD-150735

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 101-111, 2016