Journal of Alzheimer's Disease - Volume 70, issue 1

Authors: Guzik-Makaruk, Ewa M. | Pływaczewski, Emil W. | Laskowska, Katarzyna | Filipkowski, Wojciech | Jurgielewicz-Delegacz, Emilia | Mroczko, Piotr

Article Type: Review Article

Abstract: Dementia is associated with the gradual impairment of mental ability. The population of people suffering from dementia is as large as 50 million. Most dementia cases result from various neurodegenerative diseases (NDs) linked by a progressive degeneration of neurons. Among NDs, Alzheimer’s disease (AD) is the most frequent cause of dementia and accounts for 60– 80% of cases. Certain pathological changes on the cellular and subcellular level occur even 15 years before the manifestation of clinical symptoms of AD. This first asymptomatic phase of AD is considered a preclinical stage, whereas mild cognitive impairment (MCI) is the symptomatic pre-dementia stage. …The third, fully symptomatic phase of AD is dementia due to AD. The presence of specific proteins in the cerebrospinal fluid (CSF) may be considered as a characteristic feature of some NDs. The measurement of their CSF concentrations, together with neuropsychological examination and neuroimaging, may be useful for diagnosing AD. The collection of CSF samples is performed by lumbar puncture, which is a medical procedure that requires obtaining informed consent from patients. While asymptomatic AD patients have full legal capacity, those with dementia require a legal guardian who will represent them. Thus, the objective of this study is to compare the legal systems regulating the legal capacity issue in the USA, U.K. (England and Wales), Germany, and Poland. These countries have been chosen as examples of three different types of legal orders, according to the sources of law, i.e., civil law, common law, and case law. Show more

Keywords: Alzheimer’s disease, legal capacity, legal regulations, neurodegenerative diseases

DOI: 10.3233/JAD-190259

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 1-10, 2019

Authors: Monacelli, Fiammetta | Martella, Lucia | Parodi, Maria Nives | Odetti, Patrizio | Fanelli, Francesca | Tabaton, Massimo

Article Type: Short Communication

Abstract: Alzheimer’s disease may mimic frontotemporal dementia. We describe a case of presenile dementia who presented with peudo-psychotic symptoms carrying a PSEN1 mutation (P355 S), which was not known to be pathogenic. PET-FDG showed bilateral frontotemporal hypometabolism, but at MRI, multiple microbleeds were detected, suggestive of amyloid angiopathy.

Keywords: Behavioral variant, presenile dementia, presenilin 1 mutation

DOI: 10.3233/JAD-190363

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 11-15, 2019

Authors: Niu, Li-Dong | Yin, Rui | Li, Jie-Qiong | Cao, Xi-Peng | Yu, Jin-Tai | Tan, Lan | Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: A potential role for ABI3 gene has been suggested in the risk of Alzheimer’s disease (AD), but the detailed mechanism before typical AD onset was unclear. In this study, we investigated the associations of ABI3 common variants with cerebrospinal fluid biomarkers and cognitive function scores among non-demented elderly from the ADNI database. We found that, in the progressive mild cognitive impairment group, rs5978930 was associated with total tau levels and rs16947151 was associated with cognitive function scores at baseline and over time, suggesting that ABI3 variants may be associated with cognitive decline and may influence AD onset …through tau pathology. Show more

Keywords: ABI3, biomarkers, mild cognitive impairment, total tau, variant

DOI: 10.3233/JAD-190153

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 17-23, 2019

Authors: Dietlin, Simon | Soto, Maria | Kiyasova, Vera | Pueyo, Maria | de Mauleon, Adelaïde | Delrieu, Julien | Ousset, Pierre Jean | Vellas, Bruno

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) are prevalent in mild cognitive impairment (MCI), but we do not know much about their role in progression to dementia. Objective: To investigate NPS and the risk of progression to probable Alzheimer’s disease dementia (AD) among subjects with MCI. Methods: 96 MCI participants were followed for 4 years. Progression to probable AD was defined by the change of CDR total score from 0.5 to ≥1, reviewed by an expert consensus panel. NPS were determined using the Neuropsychiatric Inventory (NPI) 12-items. This study analyzed prognostic value of each NPI item and 5 sub-syndromes …of NPS (apathy, psychosis, affective, hyperactivity, and vegetative) for prediction of progression to probable AD. A Cox proportional hazard model was used; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with time dependent variable to compare the incidence of progression considering presence/absence of any NPS or sub-syndromes throughout the study. Results: The presence of symptoms “agitation/aggression”, “delusions”, and “aberrant motor behavior” significantly increased the risk of probable AD (HR = 3.9; 95% CI = 1.9–8.2; HR = 13.9; 95% CI = 4.1–48.9; HR = 4.3; 95% CI = 1.7–10.3, respectively). The presence of sub-syndromes “psychosis” and “hyperactivity” were also predictors of progression (HR = 14.0; 95% CI = 4.4–44.5; HR = 2.0; 95% CI = 1.1–3.7, respectively). These results did not change after adjusting by potential confounders. Conclusion: Presence of delusions, agitation/aggression, and aberrant motor behavior is predictor of progression to probable AD. Show more

Keywords: Alzheimer’s disease, dementia, mild cognitive impairment, neuropsychiatric symptoms

DOI: 10.3233/JAD-190025

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 25-34, 2019

Authors: Tanprasertsuk, Jirayu | Johnson, Elizabeth J. | Johnson, Mary Ann | Poon, Leonard W. | Nelson, Peter T. | Davey, Adam | Martin, Peter | Barbey, Aron K. | Barger, Kathryn | Wang, Xiang-Dong | Scott, Tammy M.

Article Type: Research Article

Abstract: Background: Centenarian studies are important sources for understanding of factors that contribute to longevity and healthy aging. Clinico-neuropathological finding is a key in identifying pathology and factors contributing to age-related cognitive decline and dementia in the oldest old. Objective: To characterize the cross-sectional relationship between neuropathologies and measures of premortem cognitive performance in centenarians. Methods: Data were acquired from 49 centenarians (≥98 years) from the Georgia Centenarian Study. Cognitive assessment from the time point closest to mortality was used (<1 year for all subjects) and scores for cognitive domains were established. Neuropathologies [cerebral atrophy, ventricular dilation, …atherosclerosis, cerebral amyloid angiopathy (CAA), Lewy bodies, hippocampal sclerosis (HS), hippocampal TDP-43 proteinopathy, neuritic plaque (NP) and neurofibrillary tangle (NFT) counts, Braak staging, and National Institute on Aging-Reagan Institute (NIARI) criteria for the neuropathological diagnosis of Alzheimer’s disease (AD)] were compared among subjects with different ratings of dementia. Linear regression was applied to evaluate the association between cognitive domain scores and neuropathologies. Results: Wide ranges of AD-type neuropathological changes were observed in both non-demented and demented subjects. Neocortical NFT and Braak staging were related to clinical dementia rating. Neocortical NFT and NP, Braak and NIARI staging, cerebral and ventricular atrophy, HS, CAA, and TDP-43 proteinopathy were differentially associated with poor performance in multiple cognitive domains and activities of daily living. Conclusion: AD-type pathology was associated with severe dementia and poor cognition but was not the only variable that explained cognitive impairment, indicating the complexity and heterogeneity of pathophysiology of dementia in the oldest old. Show more

Keywords: Alzheimer’s disease, amyloid plaques, centenarians, cognition, neurofibrillary tangles, neuropathology

DOI: 10.3233/JAD-181110

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 35-49, 2019

Authors: Park, Jee Eun | Jeon, So Yeon | Kim, Se An | Kim, Jin Ha | Kim, Seon Hwa | Lee, Kyung Won | Hwang, Yun Jung | Jung, Gijung | Suk, Hye Won | Park, Saejong | Lee, Dong Young

Article Type: Research Article

Abstract: We aimed to examine the feasibility and effectiveness of a multidomain intervention including intensive and maintenance programs for reducing the risk of dementia in at-risk older adults. Community-dwelling older adults (aged ≥60 years) without dementia but having several risk factors for dementia (N = 32; 89% female; mean age±standard deviation, 76.8±4.7 years) were assigned to three parallel programs: intensive plus maintenance (INT+MNT), intensive only (INT-only), and active control. Subjects in INT+MNT and INT-only groups participated in a 4-week intensive group-based lifestyle modification program that focused on physical activity, vascular risk factors, dietary habits, cognitive activities, and social engagement. INT+MNT participants underwent an …additional 20-week maintenance program to consolidate modified habits. The modified Australian National University-Alzheimer’s Disease Risk Index (ANU-ADRI) score was used as the primary outcome measure for dementia risk. The changes in ANU-ADRI scores exhibited a significant group-by-time interaction: the INT+MNT group showed significant improvement at 24 weeks (β= –6.05; SE = 1.86; p  = 0.002), while the INT-only group did not. Additional exploratory analyses showed that the reduction in ANU-ADRI scores was caused by changes in protective factors rather than in risk factors. The INT + MNT group also showed greater improvement in executive function at 4 and 24 weeks (both p  = 0.044), whereas changes in global cognitive function did not reach significance (p  = 0.055). A 24-week multidomain dementia prevention involving a maintenance strategy for sustaining modified lifestyle habits reduced the risk of dementia and improved executive function in at-risk older adults. Show more

Keywords: Aged, alzheimer’s disease, dementia, health promotion, risk reduction behavior

DOI: 10.3233/JAD-190016

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 51-60, 2019

Authors: Markova, Hana | Nikolai, Tomas | Mazancova, Adela Fendrych | Cechova, Katerina | Sheardova, Katerina | Georgi, Hana | Kopecek, Miloslav | Laczó, Jan | Hort, Jakub | Vyhnalek, Martin

Article Type: Research Article

Abstract: Background: Subjective cognitive complaints (SCCs) may represent an early cognitive marker of Alzheimer’s disease (AD). There is a need to identify specific SCCs associated with an increased likelihood of underlying AD. Objective: Using the Questionnaire of Cognitive Complaints (QPC), we evaluated the pattern of SCCs in a clinical sample of non-demented older adults in comparison to cognitively healthy community-dwelling volunteers (HV). Methods: In total, 142 non-demented older adults from the Czech Brain Aging Study referred to two memory clinics for their SCCs were classified as having subjective cognitive decline (SCD, n  = 85) or amnestic mild cognitive …impairment (aMCI, n  = 57) based on a neuropsychological evaluation. Furthermore, 82 age-, education-, and gender-matched HV were recruited. All subjects completed the QPC assessing the presence of specific SCCs in the last six months. Results: Both SCD and aMCI groups reported almost two times more SCCs than HV, but they did not differ from each other in the total QPC score. Impression of memory change and Impression of worse memory in comparison to peers were significantly more prevalent in both SCD and aMCI groups in comparison to HV; however, only the latter one was associated with lower cognitive performance. Conclusion: The pattern of QPC-SCCs reported by SCD individuals was more similar to aMCI individuals than to HV. A complaint about memory change seems unspecific to pathological aging whereas a complaint about worse memory in comparison to peers might be one of the promising items from QPC questionnaire potentially reflecting subtle cognitive changes. Show more

Keywords: Mild cognitive impairment, prodromal Alzheimer’s disease, questionnaire of cognitive complaints, subjective cognitive complaints, subjective cognitive decline

DOI: 10.3233/JAD-180630

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 61-73, 2019

Authors: Zakirova, Elena Y. | Chastukhina, Inna B. | Valeeva, Lia R. | Vorobev, Viacheslav V. | Rizvanov, Albert A. | Palotás, András | Shakirov, Eugene V.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a devastating slowly progressive neurodegenerative disorder with no cure. While there are many hypotheses, the exact mechanism causing this pathology is still unknown. Among many other features, AD is characterized by brain hypometabolism and decreased sugar availability, to which neurons eventually succumb. In light of this aspect of the disease, we hypothesized that boosting fuel supply to neurons may help them survive or at least alleviate some of the symptoms. Here we demonstrate that live moss Physcomitrella patens cells can be safely co-cultured with human fibroblasts in vitro and thus have a potential for …providing human cells with energy and other vital biomolecules. These data may form the foundation for the development of novel approaches to metabolic bioengineering and treatment of diseased cells based on live plants. In addition, by providing alternative energy sources to human tissues, the biotechnological potential of this interkingdom setup could also serve as a springboard to foster innovative dietary processes addressing current challenges of mankind such as famine or supporting long-haul space flight. Show more

Keywords: Alternative energy source, Alzheimer’s disease, co-cultivation, famine, fibroblast, glucose, hypometabolism, moss, natural scaffold, Physcomitrella, regenerative medicine, space flight, tissue engineering

DOI: 10.3233/JAD-190333

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 75-89, 2019

Authors: Bohlken, Jens | Jacob, Louis | Kostev, Karel

Article Type: Research Article

Abstract: Background: In recent years, there has been a growing interest in the association between the use of antihypertensive drugs and the incidence of dementia. Objective: The goal of this retrospective study was to investigate the relationship between antihypertensive drug use and dementia in elderly persons followed in general practices in Germany. Methods: This study included patients ≥60 years with documented blood pressure values who were diagnosed with dementia in general practices in Germany for the first time between 2013 and 2017 (index date). Dementia cases were matched to non-dementia controls using propensity scores based on age, …sex, index year, and co-diagnoses. The main outcome of the study was the incidence of dementia as a function of the use of antihypertensive drugs. Results: The present study included 12,405 patients with dementia and 12,405 patients without dementia. The use of angiotensin II receptor blockers (odds ratios [ORs] ranging from 0.74 to 0.79), angiotensin-converting enzyme inhibitors (ORs ranging from 0.85 to 0.88), calcium channel blockers (ORs ranging from 0.82 to 0.89), and beta blockers (OR = 0.88) was associated with a decrease in dementia incidence. Conclusion: Antihypertensive drug use is negatively associated with dementia in elderly persons followed in general practices in Germany. Show more

Keywords: Antihypertensive drugs, dementia, elderly persons, general practices, Germany

DOI: 10.3233/JAD-190362

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 91-97, 2019

Authors: Wong, Benjamin Yi Xin | Yong, Ting Ting | Lim, Levinia | Tan, Jayne Yi | Ng, Adeline Su Lyn | Ting, Simon Kang Seng | Hameed, Shahul | Ng, Kok Pin | Zhou, Juan Helen | Kandiah, Nagaendran

Article Type: Research Article

Abstract: Background: Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer’s pathophysiology (SNAP), especially in Asia. Objective: To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-β negative patients with mild amnestic type dementia. Methods: Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF Aβ levels. Neuroimaging and neuropsychological variables were analyzed. Results: Despite comparable MTA between Aβ …positive and negative patients, Aβ-negative patients had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their Aβ-positive counterparts (6.42 versus 4.19, p  = 0.03). A larger proportion of Aβ-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results. Conclusion: Our findings demonstrate that MTA is associated with greater CVD burden among Aβ-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression. Show more

Keywords: Cerebrovascular disease, medial temporal lobe, neurodegeneration, suspected non-Alzheimer’s pathophysiology, white matter hyperintensity, young onset dementia.

DOI: 10.3233/JAD-181261

Citation: Journal of Alzheimer's Disease, vol. 70, no. 1, pp. 99-106, 2019