Journal of Alzheimer's Disease - Volume 64, issue 4

Authors: Baiardi, Simone | Capellari, Sabina | Bartoletti Stella, Anna | Parchi, Piero

Article Type: Review Article

Abstract: The introduction of prion RT-QuIC, an ultrasensitive specific assay for the in vivo detection of the abnormal prion protein, has significantly increased the potential for an early and accurate clinical diagnosis of Creutzfeldt-Jakob disease (CJD). However, in the clinical setting, the early identification of patients with possible CJD is often challenging. Indeed, CJD patients may present with isolated symptoms that remain the only clinical manifestation for some time, or with neurological syndromes atypical for CJD. To enhance awareness of unusual disease presentations and promote earlier diagnosis, we reviewed the entire spectrum of atypical early manifestations of CJD, mainly reported …to date as case descriptions or small case series. They included sensory either visual or auditory disturbances, seizures, isolated psychiatric manifestations, atypical parkinsonian syndromes (corticobasal syndrome, progressive supranuclear palsy-like), pseudobulbar syndrome, isolated involuntary movements (dystonia, myoclonus, chorea, blepharospasm), acute or subacute onsets mimicking a stroke, isolated aphasia, and neuropathy. Since CJD is a rare disease and its clinical course rapidly progressive, an in-depth understanding and awareness of early clinical features are mandatory to enhance the overall diagnostic accuracy in its very early stages and to recruit optimal candidates for future therapeutic trials. Show more

Keywords: Clinical phenotype, Creutzfeldt-Jakob disease, early diagnosis, Heidenhain variant, human prions, movement disorders, neurodegenerative dementia, seizures

DOI: 10.3233/JAD-180123

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1051-1065, 2018

Authors: Schwab, Nicole | Hazrati, Lili-Naz

Article Type: Review Article

Abstract: Chronic traumatic encephalopathy (CTE) is considered to be a progressive neurodegenerative disease caused by mild traumatic brain injury (mTBI). Recently there has been a significant amount of media attention surrounding the commonness of CTE in professional athletes, particularly American football, based on several postmortem case series. However, despite the persuasive claims made by the media about CTE, research on the disease and the effects of mTBI in general remain in its infancy. Commonly cited case series studying CTE are limited by methodological biases, pathological inconsistencies, insufficient clinical data, and a reliance on inherently biased postmortem data. These case series do …not allow for the collection of any epidemiological data and are not representative of the general population. The exaggerated assumptions and assertions taken from these studies run the risk of creating a self-fulfilling prophecy for individuals who believe they are at risk and have the potential to negatively influence sports-related policymaking. This review outlines the status and limitations of recent CTE case series and calls for future prospective, longitudinal studies to further characterize the pathological and clinical hallmarks of CTE. Show more

Keywords: Athletic injury, chronic traumatic encephalopathy, concussion, dementia, neurodegeneration, tauopathies, traumatic brain injury

DOI: 10.3233/JAD-180373

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1067-1076, 2018

Authors: Beam, Christopher R. | Kaneshiro, Cody | Jang, Jung Yun | Reynolds, Chandra A. | Pedersen, Nancy L. | Gatz, Margaret

Article Type: Short Communication

Abstract: In the following brief report, we examined gender differences in incidence rates of any dementia, Alzheimer’s disease (AD) alone, and non-Alzheimer’s dementia alone in 16,926 women and men in the Swedish Twin Registry aged 65+. Dementia diagnoses were based on clinical workup and national health registry linkage. Incidence rates of any dementia and AD were greater in women than men, with any dementia rates diverging after age 85 and AD rates diverging around 80. This pattern is consistent with women’s survival to older ages compared to men. These findings are similar to incidence rates reported in other Swedish samples.

Keywords: Alzheimer’s disease, any dementia, gender differences, incidence, Swedish Twin Registry

DOI: 10.3233/JAD-180141

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1077-1083, 2018

Authors: Rocha, Natalia P. | Toledo, Andre | Corgosinho, Laiane T.S. | de Souza, Leonardo C. | Guimarães, Henrique C. | Resende, Elisa P.F. | Braz, Nayara F.T. | Gomes, Karina B. | Simoes e Silva, Ana C. | Caramelli, Paulo | Teixeira, Antonio L.

Article Type: Short Communication

Abstract: This study was designed to determine whether the levels of renin-angiotensin system (RAS) components are associated with Alzheimer’s disease (AD) pathology. Cerebrospinal fluid levels of Angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), ACE2, Amyloid-β (Aβ)40 , Aβ42, total tau (hTau), and phospho-tau (pTau) were measured in 18 patients with AD and 10 controls. Patients with AD presented decreased levels of ACE when compared with controls. We found a significant positive correlation between ACE and Aβ42 levels among patients. Our results strengthen the hypothesis that ACE is associated with Aβ pathology in AD.

Keywords: Alzheimer’s disease, amyloid-beta, angiotensin-converting enzyme, biomarkers, renin-angiotensin system

DOI: 10.3233/JAD-180282

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1085-1090, 2018

Authors: Thyrian, Jochen René | Hertel, Johannes | Schulze, Lara N. | Dörr, Marcus | Prüss, Harald | Hempel, Petra | Bimmler, Marion | Kunze, Rudolf | Grabe, Hans Jörgen | Teipel, Stefan | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: There is a need to assess promising biomarkers for diagnosis and treatment response in real-life settings. Despite the important role of vascular risk factors, cardiovascular biomarkers have played a minor role in dementia research. Agonistic autoantibodies (agAAB) directed against G-protein-coupled receptors (GPCR) are discussed as modulators of pathology and clinical manifestation. Objective: 1) Describe prevalence of agAAB directed against GPCR, especially agABB against α 1-adrenergic receptors (α 1-AR-agAAB) and agABB directed against β 2-adrenergic receptors (β 2-AR-agAAB) and 2) identify factors associated with agAAB in people with dementia during routine care. Methods: Blood samples and …data from 95 subjects who screened positive for dementia from a primary care cohort, analyzed using an enzyme-linked immunosorbent assay (ELISA) for detecting agAAB. Sociodemographic and clinical data were assessed, and medical records checked. Results: In 40 (42%) samples, agAAB was detected, with n = 29 (31%) representing α 1-AR-agAAB and n = 21 (22%) β 2-AR-agAAB. There was no association between the presence of any antibody and a formal diagnosis of dementia. However, patients with coronary heart disease were more likely (OR = 4.23) to have α 1-AR-agAAB than those without coronary heart disease. There were no associations between agAAB and age, sex, education, or cognitive impairment. Discussion: For the first time, we show that autoantibodies have a significant prevalence in people with dementia in a routine care setting. Previous findings were restricted to highly selective samples. We replicated the association between α 1-AR-agAAB in patients with coronary heart diseases but were not able to find other factors associated with the presence of agAAB. Show more

Keywords: Antibodies, biomarker, immunoadsorption, prevalence, primary care

DOI: 10.3233/JAD-171096

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1091-1097, 2018

Authors: Casamitjana, Adrià | Petrone, Paula | Tucholka, Alan | Falcon, Carles | Skouras, Stavros | Molinuevo, José Luis | Vilaplana, Verónica | Gispert, Juan Domingo | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: The identification of healthy individuals harboring amyloid pathology represents one important challenge for secondary prevention clinical trials in Alzheimer’s disease (AD). Consequently, noninvasive and cost-efficient techniques to detect preclinical AD constitute an unmet need of critical importance. In this manuscript, we apply machine learning to structural MRI (T1 and DTI) of 96 cognitively normal subjects to identify amyloid-positive ones. Models were trained on public ADNI data and validated on an independent local cohort. Used for subject classification in a simulated clinical trial setting, the proposed method is able to save 60% of unnecessary CSF/PET tests and to reduce 47% of …the cost of recruitment. This recruitment strategy capitalizes on available MR scans to reduce the overall amount of invasive PET/CSF tests in prevention trials, demonstrating a potential value as a tool for preclinical AD screening. This protocol could foster the development of secondary prevention strategies for AD. Show more

Keywords: Amyloid pathology, clinical trial, machine learning, preclinical Alzheimer’s disease, screening, secondaryprevention

DOI: 10.3233/JAD-180299

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1099-1112, 2018

Authors: Renard, Dimitri | Tatu, Lavinia | Collombier, Laurent | Wacongne, Anne | Ayrignac, Xavier | Charif, Mahmoud | Boukriche, Yassine | Chiper, Laura | Fourcade, Genevieve | Azakri, Souhayla | Gaillard, Nicolas | Mercier, Erick | Lehmann, Sylvain | Thouvenot, Eric

Article Type: Research Article

Abstract: Background: Cerebral amyloid angiopathy (CAA) can be associated with primary vasculitis of small/medium-sized leptomeningeal and cortical arteries, called CAA-related inflammation (CAA-ri). Objective: To compare hemorrhagic and diffusion-weighted imaging (DWI) MRI features in CAA and CAA-ri. Methods: We prospectively scored in a consecutive CAA and CAA-ri cohort: presence/number of chronic intracerebral hemorrhage (ICH), cerebral microbleeds (CMB), and cortical superficial siderosis (CSS) on initial T2*-weighted imaging, and DWI lesions on both initial and follow-up imaging. In a subgroup, ApoE, CSF, and 18F-florbetaben-positron emission tomography (FBB-PET) were also analyzed. Results: In CAA-ri, CMB presence was more frequent …(100% versus 40%, p < 0.001) and CMB numbers higher (mean 137 versus 8, p < 0.001). No difference was observed for chronic ICH or CSS. DWI lesions were more frequent in acute compared to chronic CAA-ri (p = 0.025), whereas no such difference was observed between acute and chronic CAA (p = 0.18). Both ApoE4 (genotyping available in 22 CAA-ri and 48 CAA patients) carriers and homozygosity were more frequent in CAA-ri (48% versus 19% [p = 0.014] and 32% versus 2% [p < 0.001] respectively). CSF biomarker analyses (performed in 20 CAA-ri and 45 CAA patients) showed lower Aβ 42 levels in CAA-ri compared to CAA (median 312 versus 422 pg/mL, p = 0.0032). FBB-PET (performed in 11 CAA-ri and 20 CAA patients) showed higher standardized uptake value ratios in CAA-ri compared with CAA, only significant when the pons was used as reference (p = 0.037). Conclusion: Compared to CAA, CAA-ri was associated with higher CMB numbers, more frequent ApoE4 carriers and homozygotes, lower CSF Aβ 42 levels, and more severe amyloid load on FBB-PET. Show more

Keywords: Amyloid imaging, apolipoprotein E genotype, cerebral amyloid angiopathy, cerebral amyloid angiopathy-related inflammation, cerebral microbleeds, cerebrospinal fluid, florbetaben, intracerebral hemorrhage, positron emission tomography

DOI: 10.3233/JAD-180269

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1113-1121, 2018

Authors: Mariani, Elena | Chattat, Rabih | Ottoboni, Giovanni | Koopmans, Raymond | Vernooij-Dassen, Myrra | Engels, Yvonne

Article Type: Research Article

Abstract: Background: Shared decision-making (SDM) can be a way for staff to adopt international recommendations advocating the involvement of nursing home residents and their family members in care planning and the development of personalized care plans. Objective: The main aim was to analyze the effects of training nursing home staff in the implementation of SDM on agreement of residents’ ‘life-and-care plans’ with the recommendations (primary outcome) and on family caregivers’ quality of life and sense of competence, and staff’s job satisfaction (secondary outcomes). Methods: In the intervention condition, staff attended a training program on the use of …SDM with residents and family caregivers in the care planning process. In the control condition, care planning as usual took place. For the primary outcome, in-depth qualitative and quantitative analyses of the care plans were performed. Multivariate Permutation Tests were applied to assess the impact on secondary outcomes. Results: Forty-nine residents and family caregivers and 34 professionals were involved. Overall, many of the care plans developed during the intervention showed a high level of agreement with the care planning recommendations. Both Italian and Dutch care plans showed improvement in the number of clear problem statements (p < 0.001). In Italy, significant improvements (p < 0.05) were also found regarding specific care objectives, documentation of objectives met, and of residents and families’ involvement. No impact was found on secondary outcomes. Conclusion: The involvement of residents and family caregivers in care planning contributed to an improvement of the residents’ care plans, but it did not have an effect on family caregivers and staff outcomes. Show more

Keywords: Care planning policy, care planning regulations, care plans, dementia residents, elderly residents, family caregivers, nursing homes, shared decision-making

DOI: 10.3233/JAD-180279

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1123-1135, 2018

Authors: Whitson, Heather E. | Potter, Guy G. | Feld, Jody A. | Plassman, Brenda L. | Reynolds, Kelly | Sloane, Richard | Welsh-Bohmer, Kathleen A.

Article Type: Research Article

Abstract: Background: Dual-task paradigms, in which an individual performs tasks separately and then concurrently, often demonstrate that people with neurodegenerative disorders experience more dual-task interference, defined as worse performance in the dual-task condition compared to the single-task condition. Objective: To examine how gait-cognition dual-task performance differs between cognitively normal older adults with and without an APOE ɛ 4 allele. Methods: Twenty-nine individuals ages 60 to 72 with normal cognition completed a dual-task protocol in which walking and cognitive tasks (executive function, memory) were performed separately and concurrently. Fourteen participants carried APOE ɛ 4 alleles (ɛ 3/ɛ 4 …or ɛ 2/ɛ 4); fifteen had APOE genotypes (ɛ 2/ɛ 2, ɛ 2/ɛ 3, or ɛ 3/ɛ 3) associated with lower risk of Alzheimer’s disease (AD). Results: The two risk groups did not differ by age, sex, race, education, or gait or cognitive measures under single-task conditions. Compared to low risk participants, APOE ɛ 4 carriers tended to exhibit greater dual-task interference. Both the memory and executive function tasks resulted in dual-task interference on gait, but effect sizes for a group difference were larger when the cognitive task was executive function. In the dual-task protocol that combined walking and the executive function task, effect sizes for group difference in gait interference were larger (0.62– 0.70) than for cognitive interference (0.45– 0.47). Discussion: Dual-task paradigms may reveal subtle changes in brain function in asymptomatic individuals at heightened risk of AD. Show more

Keywords: Aging brain, cognitive performance, cognitive reserve, dementia, diagnosis, early detection, motor interference, phenotype, risk, stress test

DOI: 10.3233/JAD-180016

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1137-1148, 2018

Authors: Ni, Hua | Xu, Min | Zhan, Gui-Lai | Fan, Yu | Zhou, Hejiang | Jiang, Hong-Yan | Lu, Wei-Hong | Tan, Liwen | Zhang, Deng-Feng | Yao, Yong-Gang | Zhang, Chen

Article Type: Research Article

Abstract: Depression is one of the most frequent psychiatric symptoms observed in people during the development of Alzheimer’s disease (AD). We hypothesized that genetic factors conferring risk of depression might affect AD development. In this study, we screened 31 genes, which were located in 19 risk loci for major depressive disorder (MDD) identified by two recent large genome-wide association studies (GWAS), in AD patients at the genomic and transcriptomic levels. Association analysis of common variants was performed by using summary statistics of the International Genomics of Alzheimer’s Project (IGAP), and association analysis of rare variants was conducted by sequencing the entire …coding region of the 31 MDD risk genes in 107 Han Chinese patients with early-onset and/or familial AD. We also quantified the mRNA expression alterations of these MDD risk genes in brain tissues of AD patients and AD mouse models, followed by protein-protein interaction network prediction to show their potential effects in AD pathways. We found that common and rare variants of L3MBTL2 were significantly associated with AD. mRNA expression levels of 18 MDD risk genes, in particular SORCS3 and OAT , were differentially expressed in AD brain tissues. 13 MDD risk genes were predicted to physically interact with core AD genes. The involvement of HACE1 , NEGR1 , and SLC6A15 in AD was supported by convergent lines of evidence. Taken together, our results showed that MDD risk genes might play an active role in AD pathology and supported the notion that depression might be the “common cold” of psychiatry. Show more

Keywords: Alzheimer’s disease, depression, genome-wide association studies, genomics, transcriptomics

DOI: 10.3233/JAD-180276

Citation: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1149-1161, 2018