Journal of Alzheimer's Disease - Volume 66, issue 4

Authors: Calderón-Garcidueñas, Lilian | Mukherjee, Partha S. | Waniek, Katharina | Holzer, Max | Chao, Chih-kai | Thompson, Charles | Ruiz-Ramos, Rubén | Calderón-Garcidueñas, Ana | Franco-Lira, Maricela | Reynoso-Robles, Rafael | Gónzalez-Maciel, Angélica | Lachmann, Ingolf

Article Type: Research Article

Abstract: Long-term exposure to fine particulate matter (PM2.5 ) and ozone (O3 ) above USEPA standards is associated with Alzheimer’s disease (AD) risk. Metropolitan Mexico City (MMC) children exhibit subcortical pretangles in infancy and cortical tau pre-tangles, NFTs, and amyloid phases 1-2 by the 2nd decade. Given their AD continuum, we measured in 507 normal cerebrospinal fluid (CSF) samples (MMC 354, controls 153, 12.82±6.73 y), a high affinity monoclonal non-phosphorylated tau antibody (non-P-Tau), as a potential biomarker of AD and axonal damage. In 81 samples, we also measured total tau (T-Tau), tau phosphorylated at threonine 181 (P-Tau), amyloid-β1-42 , BDNF, and …vitamin D. We documented by electron microscopy myelinated axonal size and the pathology associated with combustion-derived nanoparticles (CDNPs) in anterior cingulate cortex white matter in 6 young residents (16.25±3.34 y). Non-P-Tau showed a strong increase with age significantly faster among MMC versus controls (p  = 0.0055). Aβ1 - 42 and BDNF concentrations were lower in MMC children (p  = 0.002 and 0.03, respectively). Anterior cingulate cortex showed a significant decrease (p  = <0.0001) in the average axonal size and CDNPs were associated with organelle pathology. Significant age increases in non-P-Tau support tau changes early in a population with axonal pathology and evolving AD hallmarks in the first two decades of life. Non-P-Tau is an early biomarker of axonal damage and potentially valuable to monitor progressive longitudinal changes along with AD multianalyte classical CSF markers. Neuroprotection of young urbanites with PM2.5 and CDNPs exposures ought to be a public health priority to halt the development of AD in the first two decades of life. Show more

Keywords: Aβ1-42, air pollution, Alzheimer’s disease, axonal damage, BDNF, cerebrospinal fluid, children, combustion-derived nanoparticles, insulin, leptin, Mexico City, non-phosphorylated tau, PM2.5 , PrPC , vitamin D, Wallerian degeneration, white matter

DOI: 10.3233/JAD-180853

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1437-1451, 2018

Authors: Lu, Zhihui | Harris, Tamara B. | Shiroma, Eric J. | Leung, Jason | Kwok, Timothy

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is the most common form of dementia, and mild cognitive impairment (MCI) is a transitional phase between healthy cognition and dementia. Physical activity (PA) has protective effects on cognitive decline. However, few studies have examined how PA and sedentary behavior is structured throughout the day in older adults across varied cognitive status in Hong Kong. Objective: This study aimed to compare patterns of PA and sedentary behavior among individuals with AD, MCI, or normal cognition living in Hong Kong. Methods: Participants in the MrOs and MsOs Hong Kong cohort study and the …Hong Kong AD biomarker study (n  = 810) wore a wrist-worn accelerometer for 7 days in free-living environment. Patterns of PA in wake time and in-bed time, and detailed analysis of sedentary bouts were compared between groups using analysis of covariance adjusting for covariates. Results: Participants with MCI and low MoCA only did not differ from their cognitively normal peers in PA and sedentary behavior. Nevertheless, when comparing to the others, participants with AD exhibited significantly lower average daily counts per minute during the day (p  < 0.05), and tended to start their activity later in the morning. AD participants spent a larger proportion of time in sedentary behavior (p  < 0.05) and had more sedentary bouts≥30 minutes (p  < 0.05). Conclusions: The pattern of PA and sedentary behavior was different between individuals with AD and the others. Cognitive status may alter the purpose and type of PA intervention for AD individuals. Show more

Keywords: Accelerometry, Alzheimer’s disease, cognitive decline, exercise, mild cognitive impairment

DOI: 10.3233/JAD-180805

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1453-1462, 2018

Authors: Palm, Rebecca | Sorg, Christian G.G. | Ströbel, Armin | Gerritsen, Debby L. | Holle, Bernhard

Article Type: Research Article

Abstract: Background: The phenomena of severe agitation is not well understood and often not adequately treated. Objective: This article determines the prevalence and associated factors of severe agitation in nursing home residents with dementia. Methods: Secondary data analysis within an observational study in German nursing homes with n  = 1,967 participants. We assessed severity of agitation with the Neuropsychiatric Inventory Questionnaire (NPI-Q) and defined the construct of agitation as a composite score of the NPI-Q items agitation/aggression, disinhibition, and irritability/lability; the dependent variable of severe agitation was considered as being present in residents who scored ‘severe’ in at …least one of these symptoms. A binary logistic regression model was calculated to estimate associations. Results: The prevalence of severe agitation was 6.3% (n  = 124). The strongest associations were found for elation/euphoria (OR 7.6, CI 3.1–18.5), delusions (OR 7.3, CI 4.0–13.2), apathy/indifference (OR 2.8, CI 1.7–4.7), anxiety (OR 2.2, CI 1.2–3.8), nighttime behaviors (OR 2.4, CI 1.4–4.2), motor disturbances (OR 2.4, CI 1.4–4.1), and male sex (OR 2.4. CI 1.3–4.2). Conclusion: Severe agitation in nursing home residents with dementia is a relevant clinical issue as approximately 70% of residents have a dementia. Residents with elation/euphoria and delusions may have a stronger risk of showing severe agitation. We consider delusions as a possible cause of agitation and therefore a prelude to agitation. Although it might be possible that elation/euphoria follows from agitation, we hypothesize that the residents first experience elation/ euphoria and exhibit agitation afterwards. Show more

Keywords: Aggression, agitation, dementia, nursing home, prevalence

DOI: 10.3233/JAD-180647

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1463-1470, 2018

Authors: Bacigalupo, Ilaria | Mayer, Flavia | Lacorte, Eleonora | Di Pucchio, Alessandra | Marzolini, Fabrizio | Canevelli, Marco | Di Fiandra, Teresa | Vanacore, Nicola

Article Type: Research Article

Abstract: Background: Dementia, including Alzheimer’s disease (AD), is one of the most burdensome medical conditions. Usually, the reviews that aim at calculating the prevalence of dementia include estimates from studies without assessing their methodological quality. Alzheimer’s Disease International (ADI) proposed a score to assess the methodological quality of population-based studies aimed at estimating the prevalence of dementia. During the last three years, the European Commission has funded three projects (Eurodem, EuroCoDe, and ALCOVE) in order to estimate the prevalence of dementia in Europe. Objective: The aim of this study was to perform a systematic review and meta-analysis of data …on the prevalence of dementia in Europe derived from studies that included only subjects with a diagnosis of dementia according to the DSM IV criteria, and that had a high quality score according to ADI criteria. Methods: We considered the studies selected by the two projects EuroCoDe (1993–2007) and Alcove (2008–2011), and we performed a new bibliographic search. For the systematic review, we only selected the subset of articles that included subjects with a diagnosis of dementia according to the DSM IV criteria. The studies were qualitatively assessed using the ADI tool. Results: The meta-analysis considered 9 studies that were carried out in Europe between 1993 and 2018 including a total of 18,263 participants, of which 2,137 were diagnosed with dementia. The prevalence rate standardized for age and sex resulted 7.1%. Discussion: This is the first systematic review on the prevalence of dementia in Europe considering only high-quality studies adopting the same diagnostic criteria (i.e., DSM IV). Show more

Keywords: Dementia epidemiology, prevalence studies, systematic review

DOI: 10.3233/JAD-180416

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1471-1481, 2018

Authors: Leandro, Giovana Silva | Evangelista, Adriane Feijó | Lobo, Romulo Rebouças | Xavier, Danilo Jordão | Moriguti, Julio César | Sakamoto-Hojo, Elza Tiemi

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is an age-related neurodegenerative pathology associated with accumulation of DNA damage. Inflammation and cell cycle alterations seem to be implicated in the pathogenesis of AD, although the molecular mechanisms have not been thoroughly elucidated to date. The aim of the present study was to evaluate whether peripheral blood mononuclear cells (PBMCs) of AD patients display alterations in gene expression profiles, focusing on finding markers that might improve the diagnosis of AD. Blood samples were collected from 22 AD patients and 13 healthy individuals to perform genome-wide mRNA expression. We found 593 differentially expressed genes in AD compared …to controls, from which 428 were upregulated, and 165 were downregulated. By performing a gene set enrichment analysis, we observed pathways involved in inflammation, DNA damage response, cell cycle, and neuronal processes. Moreover, functional annotation analyses indicated that differentially expressed genes are strongly related to pathways associated with the cell cycle and the immune system. The results were compared with those of an independent study on hippocampus samples, and a number of genes in common between both studies were identified as potential peripheral biomarkers for AD, including DUSP1, FOS, SLC7A2, RGS1, GFAP, CCL2, ANGPTL4, and SSPN . Taken together, our results demonstrate that PBMCs of AD patients do present alterations in gene expression profiles, and these results are comparable to those previously reported in the literature for AD neurons, supporting the hypothesis that blood peripheral mononuclear cells express molecular changes that occur in the neurons of AD patients. Show more

Keywords: Alzheimer’s disease, gene expression profiles, neurodegenerative disorders, peripheral blood cells

DOI: 10.3233/JAD-170205

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1483-1495, 2018

Authors: Sulmont-Rossé, Claire | Gaillet, Marie | Raclot, Carine | Duclos, Michel | Servelle, Maud | Chambaron, Stéphanie

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is often associated with feeding difficulties and changes in eating behavior with may lead to malnutrition. In French nursing homes, AD patients may live in special care units that better meet dementia residents’ needs. However, meals are often delivered to AD patients by using meal trays coming from central kitchens. This led to the disappearance of cues that could help residents to foresee mealtime, such as the smell of food odors. The aim of the present study was to assess the impact of odorizing the dining room of AD Units with a meat odor before lunch on …subsequent food intake and eating behavior. Thirty-two residents (>75 years old) from three AD Units were included in the study. They participated in two control lunches and two primed lunches, for which a meat odor was diffused in the dining room 15 minutes before the arrival of the meal tray (olfactory priming). Results of the first replication showed a significant effect of olfactory priming, with a 25% increase in meat and vegetable consumption compared to the control condition. Behavioral measurements also showed a significant increase of resident’s interest toward the meal in the primed lunch. However, this effect was no longer observed when the priming session was replicated two weeks later with the same priming odor and the same menu. Although further research is needed to understand why this priming effect cannot be replicated, our experiment is one of the very first to investigate the effect of food odor priming on subsequent food intake in AD patients in a real-life setting. Show more

Keywords: 80 and over, aged, Alzheimer’s disease, dementia, eating, institutionalization, malnutrition, meals, nursing home, odor, priming

DOI: 10.3233/JAD-180465

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1497-1506, 2018

Authors: Michaud, Tzeyu L. | Siahpush, Mohammad | Farazi, Paraskevi A. | Kim, Jungyoon | Yu, Fang | Su, Dejun | Murman, Daniel L.

Article Type: Research Article

Abstract: Background: Association between high adiposity and the clinical progression of dementia remains puzzling. Objective: To separately examine the association between body mass index (BMI) and cognitive, functional, and behavioral declines before, at, and after diagnosis of dementia, and further stratified by age groups, and sex. Methods: A total of 1,141 individuals with incident dementia were identified from the Uniform Data Set of the National Alzheimer’s Coordinating Center. Cognitive function was evaluated by Mini-Mental State Exam, functional abilities were assessed using Functional Activities Questionnaire, and behavioral symptoms were captured by Neuropsychiatric Inventory Questionnaire at each follow-up visit. …We used separate linear-mixed effects models to examine the association. Results: Compared to moderate baseline BMI, high baseline BMI was associated with 0.30-point slower annual progression rates in functional decline. For individuals aged 76 and over, high baseline BMI was associated with 0.42-point faster progression rates in cognitive decline annually. A U-shaped association between baseline BMI and cognitive decline was observed among men. Conclusion: BMI levels before dementia diagnosis may facilitate the identification of different risk profiles for progression rates of cognitive and functional declines in individuals who developed dementia. Show more

Keywords: Behavior, body mass index, cognition, dementia, disease progression, neuropsychological tests, public health

DOI: 10.3233/JAD-180278

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1507-1517, 2018

Authors: Piriz, Angel | Reyes, Dolly | Narkhede, Atul | Guzman, Vanessa A. | Viqar, Fawad | Meier, Irene B. | Budge, Mariana | Mena, Pedro | Dashnaw, Stephen | Lee, Joseph | Reitz, Christiane | Gutierrez, Jose | Campos, Luis | Medrano, Martin | Lantigua, Rafael | Mayeux, Richard | Brickman, Adam M.

Article Type: Research Article

Abstract: The incidence and prevalence of Alzheimer’s disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on …the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status. Show more

Keywords: Alzheimer’s disease, cerebrovascular disease, developing countries, neurodegeneration

DOI: 10.3233/JAD-180807

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1519-1528, 2018

Authors: Angermann, Susanne | Schier, Johannes | Baumann, Marcus | Steubl, Dominik | Hauser, Christine | Lorenz, Georg | Günthner, Roman | Braunisch, Matthias C. | Kemmner, Stephan | Satanovskij, Robin | Haller, Bernhard | Heemann, Uwe | Lehnert, Thomas | Bieber, Richard | Pachmann, Martin | Braun, Jürgen | Scherf, Julia | Schätzle, Gabriele | Fischereder, Michael | Grimmer, Timo | Schmaderer, Christoph

Article Type: Research Article

Abstract: Background: The prevalence of cognitive impairment in hemodialysis patients is notably high. In previous studises performed in the general population, cognitive impairment has been associated with increased mortality. Objective: We evaluated the relationship between global cognitive function tested by a short screening instrument and mortality in hemodialysis patients. Methods: Cognitive testing was performed in 242 maintenance hemodialysis patients under standardized conditions at baseline using the Montreal Cognitive Assessment (MoCA). Cognitive impairment was defined as a MoCA test score ≤24 points, as published previously. All-cause mortality was monitored during a median follow-up of 3.54 years. Kaplan-Meier plot …and Cox regression model adjusted for known risk factors for mortality in hemodialysis patients were used to examine a possible association between global cognitive function and all-cause mortality. Results: A MoCA test score ≤24 points resulted in a significant almost 3-fold higher hazard for all-cause mortality (unadjusted hazard ratio [HR]: 2.812; 95% confidence interval [95% CI]: 1.683–4.698; p  < 0.001). After adjustment, this association was attenuated but remained significant (adjusted HR: 1.749; 95% CI: 1.007–3.038; p  = 0.047). Conclusion: Impairment of global cognitive function measured by a short screening instrument was identified for the first time as an independent predictor of all-cause mortality in hemodialysis patients. Thus, implementing the MoCA test in clinical routine could contribute to a better risk stratification of this patient population. Show more

Keywords: Cognitive dysfunction, hemodialysis, Montreal Cognitive Assessment, mortality

DOI: 10.3233/JAD-180767

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1529-1537, 2018

Authors: Soria, Jose A. | Huisa, Branko N. | Edland, Steven D. | Litvan, Irene | Peavy, Guerry M. | Salmon, David P. | Hansen, Lawrence A. | Galasko, Douglas R. | Brewer, James B. | González, Hector M. | Rissman, Robert A.

Article Type: Research Article

Abstract: Clinical, neuropsychological, and neurological procedures used to diagnose Alzheimer’s disease (AD) and related dementias were largely developed and validated in well-educated, non-Latino, English-speaking populations. Sociocultural and genetic differences in Latinos might influence the accuracy of clinical diagnosis of AD and other dementias. We aim to compare the accuracy of the clinical diagnosis of AD and related dementias in Latinos with the corresponding neuropathological diagnosis. From the UCSD Alzheimer’s Disease Research Center longitudinal cohort, we selected all Latino participants who had autopsy neuropathological studies from 1991 to 2017. Participants underwent annual neurological clinical evaluations, standard neuropsychological tests, neuroimaging, and genotyping of …Apolipoprotein E. We calculated the sensitivity and specificity of the clinical diagnosis of AD against the primary pathological diagnosis. Of the 34 participants with a primary neuropathological diagnosis of AD, 33 (97.1%) were correctly clinically diagnosed as having AD at the last clinical evaluation, and 1 was incorrectly diagnosed with dementia with Lewy bodies. Of the 19 participants without a primary neuropathological diagnosis of AD, 8 were incorrectly clinically diagnosed with probable AD at the last clinic evaluation. The clinical diagnosis of AD at the last clinical evaluation had 97.1% sensitivity and 57.9% specificity for autopsy-verified AD. In this Latino cohort, clinicians predicted AD pathological findings with high sensitivity but moderate specificity. Tangle-only dementia was the most common misdiagnosis. Our study suggests that current procedures and instruments to clinically determine AD in Latinos have high sensitivity compared with neuropathology, but specificity needs to be improved. Show more

Keywords: Alzheimer’s disease, dementia, Latino, Lewy bodies, neuropathology

DOI: 10.3233/JAD-180789

Citation: Journal of Alzheimer's Disease, vol. 66, no. 4, pp. 1539-1548, 2018