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Alzheimer Disease and Associated Disorders

Nozomi Takeshima, Keita Ishiwata, Takashi Sozu, Toshi A Furukawa
This study examined the primary and secondary endpoints used by recent phase II/III randomized controlled trials (RCTs) of drugs for the Alzheimer disease. We searched the Clinical database to identify all RCTs registered from January 1, 2011 until August 19, 2018. We identified 122 RCTs and examined primary and secondary endpoints most commonly used. The median number of primary endpoints was 1 (range: 1 to 48) and the median number of secondary endpoints was 4 (range: 1 to 19). Cognitive function was used as a primary endpoint by 59% of the RCTs identified...
February 5, 2019: Alzheimer Disease and Associated Disorders
John Alexander, Thomas Ströbel, Marianthi Georgitsi, Selma Hönigschnabl, Angelika Reiner, Peter Fischer, Margaritis Tsifintaris, Peristera Paschou, Gabor G Kovacs
PURPOSE: Understanding the healthy brain aging process is key to uncover the mechanisms that lead to pathologic age-related neurodegeneration, including progression to Alzheimer disease (AD). We aimed to address the issue of pathologic heterogeneity that often underlies a clinical AD diagnosis. METHODS: We performed a deep whole-genome sequencing study aiming to identify variants that are associated specifically with healthy brain aging. PATIENTS: We examined samples from the community-based longitudinal Vienna Transdanubian Aging study comparing neuropathologically "healthy" aging in individuals above 80 years of age with pure AD patients of the same age...
January 23, 2019: Alzheimer Disease and Associated Disorders
Radmila T Tsoy, Saule T Turuspekova, Nina K Klipitskaya, Alibek Mereke, Robert G Cumming
BACKGROUND: There have been no epidemiological studies of mild cognitive impairment (MCI) in Central Asia. OBJECTIVE: The objective of this study was to describe the prevalence of, and risk factors for, MCI in an urban population in Kazakhstan. METHODS: Adults aged 60 years and over were randomly selected from registers of 15 polyclinics in Almaty. Of 790 eligible people, 668 agreed to participate (response rate 85%). Subjects were screened using the Montreal Cognitive Assessment (MoCA)...
January 23, 2019: Alzheimer Disease and Associated Disorders
Jennifer S Albrecht, Maya Hanna, Rhonda L Randall, Dure Kim, Eleanor M Perfetto
PURPOSE: Identification of Alzheimer disease and related dementias (ADRD) subtypes is important for pharmacologic treatment and care planning, yet inaccuracies in dementia diagnoses make ADRD subtypes hard to identify and characterize. The objectives of this study were to (1) develop a method to categorize ADRD cases by subtype and (2) characterize and compare the ADRD subtype populations by demographic and other characteristics. METHODS: We identified cases of ADRD occurring during 2008 to 2014 from the OptumLabs Database using diagnosis codes and antidementia medication fills...
January 23, 2019: Alzheimer Disease and Associated Disorders
Shea J Andrews, G Peggy McFall, Roger A Dixon, Nicolas Cherbuin, Ranmalee Eramudugolla, Kaarin J Anstey
PURPOSE: We investigated the association of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and an Alzheimer disease (AD) genetic risk score (GRS) with cognitive performance. METHODS: The ANU-ADRI (composed of 12 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modeling was used to evaluate the association of the ANU-ADRI and GRS with: (1) general cognitive ability (g), (2) dementia-related variance in cognitive performance (δ), and (3) verbal ability (VA), episodic memory (EM), executive function (EF), and processing speed (PS)...
January 23, 2019: Alzheimer Disease and Associated Disorders
Frances M Lissemore, Stephanie Shatzman, Nicholas Clark, Jessica Nash, Rachel Miller, Alan J Lerner
BACKGROUND: Persons with dementia (PWD) reported missing are known to be at high risk for mortality. Analysis of online search engines' reports of missing PWD may show patterns in the data of this relatively common event and the broad patterns relevant to mortality risk factors. METHODS: We searched Google news for PWD reported missing for 2015. Demographics, personal details, and outcomes were recorded. RESULTS: Of 673 cases, 67 were found deceased, 525 alive, and the remainder had unknown outcomes...
January 23, 2019: Alzheimer Disease and Associated Disorders
Rosanna Squitti, Armando Mendez, Camillo Ricordi, Mariacristina Siotto, Ron Goldberg
Trace metal dyshomeostasis has been linked to loss of cognitive performance. In particular, a disturbance in the regulation of copper (Cu), characterized by an increase in circulating Cu not bound to ceruloplasmin (non-Cp Cu), is thought to play a role in the development of Alzheimer disease (AD) and other neurodegenerative diseases in the aging population. Non-Cp Cu is redox active and its toxicity is thought to result from its ability to accelerate oxidative stress and advanced glycation endproduct (AGE) formation, leading to extracellular matrix damage in tissues including the brain...
January 10, 2019: Alzheimer Disease and Associated Disorders
Camilla Ferrari, Cristina Polito, Sara Vannucchi, Irene Piaceri, Silvia Bagnoli, Gemma Lombardi, Giulia Lucidi, Valentina Berti, Benedetta Nacmias, Sandro Sorbi
BACKGROUND/AIMS: Few longitudinal studies have explored the progression of cognitive and functional impairment of patients with primary progressive aphasia (PPA). The aims of the study were to describe the clinical, neuroimaging, and genetic features of a cohort of 68 PPA patients, and to outline the natural history of the disease. MATERIALS AND METHODS: A sample of 23 patients with the logopenic variant, 26 with the nonfluent/agrammatic variant, and 19 with the semantic variant was retrospectively collected and followed-up for a maximum of 6 years...
January 10, 2019: Alzheimer Disease and Associated Disorders
Noa Bregman, Gitit Kavé, Anat Mirelman, Avner Thaler, Mali Gana Weisz, Anat Bar-Shira, Avi Orr-Urtreger, Nir Giladi, Tamara Shiner
Cognitive deficits beyond memory impairment, such as those affecting language production or executive functioning, can be useful in clinically distinguishing between dementia syndromes. We tested the hypothesis that Ashkenazi Jewish (AJ) patients who have dementia with Lewy bodies (DLB) and carry glucocerebrosidase (GBA) mutations will have verbal fluency deficits different from those found in Alzheimer's disease (AD), whereas AJ patients with DLB who have no GBA mutations will have similar deficits in verbal fluency to those found in AD...
January 10, 2019: Alzheimer Disease and Associated Disorders
Ana S Costa, Regina Jokel, Alberto Villarejo, Sara Llamas-Velasco, Kimiko Domoto-Reilley, Jennifer Wojtala, Kathrin Reetz, Álvaro Machado
BACKGROUND: Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive deterioration of language. Being rare, reports of PPA in multilingual individuals are scarce, despite more than half of the world population being multilingual. METHODS: We describe clinical characteristics of 33 bilingual patients with PPA, including symptom presentation and language deficits pattern in their first (L1) and second language (L2), through a systematic literature review and new cases retrospectively identified in 5 countries...
January 10, 2019: Alzheimer Disease and Associated Disorders
Giulia Perini, Matteo Cotta Ramusino, Elena Sinforiani, Diego Franciotta, Giusppe Trifirò, Mauro Ceroni, Alfredo Costa
The use of biomarkers has recently supported the association between Alzheimer's disease (AD) pathology and the logopenic variant of primary progressive aphasia (PPA). We aim to investigate possible differences in cerebrospinal fluid (CSF) biomarker concentrations in the three PPA variants, and to assess any agreement between CSF biomarkers and (18)F-florbetapir PET. A group of 10 PPA were retrospectively enrolled. Patients with logopenic variant (lvPPA) showed different levels of Aβ1-42 and p-tau compared to nonfluent/agrammatic and semantic variants (nfv/svPPA)...
January 10, 2019: Alzheimer Disease and Associated Disorders
Jee-Young Han, Lilah M Besser, Chengjie Xiong, Walter A Kukull, John C Morris
INTRODUCTION: We investigated whether cholinesterase inhibitors (ChEIs) benefit cognitive outcomes in mild cognitive impairment due to Alzheimer disease (MCI-AD) and in mild AD dementia (ADdem). METHODS: Data from 2242 individuals, clinically diagnosed with MCI-AD [Clinical Dementia Rating (CDR), 0 or 0.5] or with mild ADdem (CDR, 0.5 or 1), were available from the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). General linear mixed models were used to examine the annual change in the CDR Sum of Boxes (CDR-SB) and in neuropsychological performance...
January 10, 2019: Alzheimer Disease and Associated Disorders
Kevin Duff, Kevin P Horn, John M Hoffman
PURPOSE: Longitudinal studies into the variability of F-Flutemetamol uptake are lacking. METHODS/PATIENTS: Therefore, the current study examined change in F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. RESULTS: Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0...
January 8, 2019: Alzheimer Disease and Associated Disorders
Ross Bicknell, Briohny Kennedy, Tony Pham, Lyndal Bugeja, Joseph E Ibrahim
Although people with dementia are prone to the risk of fire and burn injuries, the relationship between fatal thermal injuries and dementia has not been investigated. We examined coronial files in the state of Victoria, Australia between July 1, 2000 and December 31, 2014, for unintentional thermal injury causing deaths of community dwelling people, aged 65 years and older to identify those with dementia. Mortality for Victorian populations with and without dementia was calculated using direct age standardization...
January 8, 2019: Alzheimer Disease and Associated Disorders
Brittany DeFeis, Silvia Chapman, Carolyn Zhu, Martina Azar, Preeti Sunderaraman, Katherine Ornstein, Yian Gu, Stephanie Cosentino
OBJECTIVE: The objective of this study was to examine whether reduced awareness of memory deficits in individuals with dementia is associated with more frequent need for Medicare home health care services. METHODS: Cross-sectional analyses were conducted in a multicenter, clinic-based cohort. In total, 192 participants diagnosed with dementia and their informants were independently asked whether or not the participant demonstrated cognitive symptoms of dementia related to memory and word-finding...
December 6, 2018: Alzheimer Disease and Associated Disorders
Kavon Javaherian, Brianne M Newman, Hua Weng, Jason Hassenstab, Chengjie Xiong, Dean Coble, Anne M Fagan, Tammie Benzinger, John C Morris
INTRODUCTION: The relationships between Alzheimer disease (AD), cognitive performance, and depression are poorly understood. It is unclear whether depressive features are a prodrome of AD. In addition, some studies of aging exclude depressed individuals, which may inappropriately limit generalizability. The aim of the present study was to determine whether depressive symptoms affect cognitive function in the context of preclinical AD. METHODS: Cross-sectional multivariate analysis of participants in a longitudinal study of aging (n=356) that evaluates the influence of depressive symptoms on cognitive function in cognitively normal adults...
November 26, 2018: Alzheimer Disease and Associated Disorders
Corinne Pettigrew, Yi Shao, Yuxin Zhu, Maura Grega, Rostislav Brichko, Mei-Cheng Wang, Michelle C Carlson, Marilyn Albert, Anja Soldan
BACKGROUND: Few studies have examined the relationship between lifestyle activity engagement and cognitive trajectories among individuals who were cognitively normal at baseline. OBJECTIVE: To examine the relationship of current engagement in lifestyle activities to previous cognitive performance among individuals who were cognitively normal at baseline, and whether this relationship differed for individuals who subsequently developed mild cognitive impairment (MCI), or by APOE-4 genotype, age, and level of cognitive reserve...
October 29, 2018: Alzheimer Disease and Associated Disorders
Bieke Van Deun, Nele Van Den Noortgate, Anke Van Bladel, Tanneke Palmans, Dirk Cambier
BACKGROUND: Dementia is associated with impairment in gait, balance, and fine motor function. Paratonia, a form of hypertonia, is often present in severe dementia. However, little is known about muscle tone in early dementia, and the eventual relation between muscle tone abnormalities and changes in fine and gross motor function. METHODS: Three groups of participants were included in the study: healthy controls (n=60), participants with mild dementia (MiD) (n=31), and participants with moderate dementia (n=31)...
October 26, 2018: Alzheimer Disease and Associated Disorders
Jennifer S Albrecht, Maya Hanna, Dure Kim, Eleanor M Perfetto
INTRODUCTION: Prior studies have reported higher health care utilization (HCU) leading up to diagnosis of the Alzheimer disease and related dementia (ADRD), but none have assessed variation in HCU by ADRD subtype or examined disease-specific HCU. The objectives of this study were to identify ADRD subtypes and: (1) characterize all-cause and (2) disease-specific HCU during the 3 years preceding diagnosis, and (3) determine if HCU varied by ADRD subtype. METHODS: We used data from the OptumLabs Data Warehouse 2008 to 2014 to identify ADRD subtypes (total N=36,838) using an algorithm based on temporal sequencing of diagnoses and provider type...
October 5, 2018: Alzheimer Disease and Associated Disorders
Lilah Besser, Walter Kukull, David S Knopman, Helena Chui, Douglas Galasko, Sandra Weintraub, Gregory Jicha, Cynthia Carlsson, Jeffrey Burns, Joseph Quinn, Robert A Sweet, Katya Rascovsky, Merilee Teylan, Duane Beekly, George Thomas, Mark Bollenbeck, Sarah Monsell, Charles Mock, Xiao Hua Zhou, Nicole Thomas, Elizabeth Robichaud, Margaret Dean, Janene Hubbard, Mary Jacka, Kristen Schwabe-Fry, Joylee Wu, Creighton Phelps, John C Morris
INTRODUCTION: In 2015, the US Alzheimer's Disease Centers (ADC) implemented Version 3 of the Uniform Data Set (UDS). This paper describes the history of Version 3 development and the UDS data that are freely available to researchers. METHODS: UDS Version 3 was developed after years of coordination between the National Institute on Aging-appointed Clinical Task Force (CTF), clinicians from ∼30 ADCs, and the National Alzheimer's Coordinating Center (NACC). The CTF recognized the need for updates to align with the state of the science in dementia research, while being flexible to the diverse needs and diseases studied at the ADCs...
October 2018: Alzheimer Disease and Associated Disorders
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