bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of culturally appropriate clinical research education materials in Alzheimer’s disease and related dementias (ADRD) for Hispanic/Latino caregivers and at‐risk individuals
Authors: Shakur Mujaahida , Massett Holly A , McGowan Melissa , Gallop‐Goodman Gerda , Mitchell Alexandra K , Simoneau Elizabeth , Rehberg Kathryn , Burke Panne , Bui Elise 
Published: December 2021

AbstractBackgroundThough Hispanics/Latinos (H/L) comprise 18% of the U.S. population and are 1.5 times at greater risk for Alzheimer’s and related dementias (AD/ADRD) than non‐Hispanic Whites, a median of only 2% of participants in NIH‐funded AD/ADRD clinical trials are H/L. Reasons abound for this inequity; key documented impediments to enrollment of Latinos are too few researchers offering studies and limited materials that provide culturally and linguistically relevant information. This abstract presents findings from focus groups conducted by the National Institute on Aging (NIA) to identify salient, culturally appropriate message concepts that raise awareness, address barriers, and motivate H/L to consider participation in AD/ADRD studies.MethodTwelve remote focus groups (N=72) were conducted among two H/L audiences: 1) those at risk for AD/ADRD; and 2) those caring for a family member or friend with AD/ADRD. Messages were designed to motivate H/L to learn more about AD/ADRD clinical studies. Sessions explored participants’ knowledge, attitudes, and beliefs regarding AD/ADRD and clinical studies. Participants reviewed and provided feedback on messaging designed to motivate them to seek more information about AD/ADRD clinical studies.ResultMessage concepts that resonated strongly were those that 1) framed clinical studies as one step to finding a cure for AD/ADRD and 2) connected participation with helping their family members’ future health. Concepts were more acceptable if they represented multi‐generational families, emphasized the importance of family support, and promoted diversity and inclusivity (showing a diversity of age, gender, skin tone). Participants requested that concepts offered more opportunities to learn about Alzheimer’s and local clinical studies. Trusted concepts are those that clearly identified the document’s source and avoided the terms “trial” and “dementia,” as both had negative connotations in the Spanish language.ConclusionThe data from these focus groups improve our understanding of message concepts that motivate H/L to consider participating in AD/ADRD clinical research. They also provide insights to develop, finalize and make available to the research community a suite of culturally appropriate, well‐tested materials for H/L populations in both English and Spanish that can be used to increase awareness of AD/ADRD and clinical research.
Serum immunoglobulins and biomarkers of dementia: A population‐based study
Authors: Yaqub Amber , Khan Samer R. , Wolters Frank J. , Vernooij Meike W. , Dalm Virgil A.S.H. , Ikram M. Arfan , Chaker Layal 
Published: December 2021

AbstractBackgroundDementia is a complex syndrome with multiple interacting pathways leading to brain damage and ultimately the clinical manifestation. In recent years, studies have identified the immune response as a novel contributing process to the aetiology of dementia, but it remains unclear how this links to established biomarkers of dementia, for instance those measured in plasma or on neuroimaging. We studied the association of serum immunoglobulins, markers of the adaptive immune response, with biomarkers of dementia.MethodBetween 1997 and 2009, serum immunoglobulins (IgA, IgG and IgM) were measured in 8,768 participants of the population‐based Rotterdam Study (median age 62.2 years, 57.0% women). Plasma biomarkers of dementia (total tau, neurofilament light chain (NfL), amyloid‐β40 (Aβ‐40), amyloid‐β42 (Aβ‐42)) were measured in a random sample of 3,455 participants. Neuroimaging was performed for 3,139 participants to quantify brain volume, white matter structural integrity and markers of cerebral small vessel disease. We used linear regression models to determine cross‐sectional associations of IgA, IgG, IgM and biomarkers of dementia in plasma and on neuroimaging, while adjusting for age, sex, cohort, education, cardiovascular risk factors and stratifying for APOE‐ε4 carriership. Plasma biomarkers were log2 transformed and neuroimaging markers were standardized to facilitate comparison.ResultHigher levels of IgA corresponded to higher log2 plasma levels of NfL (β=0.019, p=0.031), and a lower or higher tau and Aβ burden, depending on carriership of the APOE‐ε4 allele. Higher IgM was consistent with lower levels of all plasma biomarkers, particularly among no carriers of the APOE‐ε4 allele. No significant associations were found between IgG levels and plasma biomarkers, although associations were moderately driven by APOE‐ε4 allele carriership. Subsequently, higher serum immunoglobulin levels and in particular IgA, generally amounted to more brain atrophy (total brain volume (β=‐0.013, p=0.032), gray matter volume (β=‐0.026, p=0.009), decreased white matter integrity and increase of cerebral small vessel disease markers (white matter hyperintensities (β=0.041, p=0.008)).ConclusionThe associations between serum immunoglobulins and biomarkers of dementia in plasma partly depend on APOE‐ε4 carriership. Higher serum immunoglobulins generally correspond to more brain atrophy, diminished white matter integrity and more cerebral small vessel disease.
Peroxisome Proliferator‐Activated Receptor γ is involved in the neuroprotection exerted by 2‐hydroxydocosahexaenoic acid against Alzheimer’s disease
Authors: Parets Sebastià , Miralles Marc , Fiol de‐Roque Maria A , Trujillo‐Estrada Laura , Cabot Joan , Péter Mária , Balogh Gábor , Fernández‐García Paula , Lladó Victoria , Busquets Xavier , Gutierrez Antonia , Escriba Pablo V. , Torres Manuel 
Published: December 2021

AbstractBackgroundDHA‐H (2‐hydroxy‐docosahexaenoic acid) is a promising therapeutic approach for Alzheimer’s Disease (AD). DHA‐H gives rise to dose‐dependent increased levels of HPA (Heneicosapentaenoic acid) in blood plasma and brain whereas DHA‐H remains virtually absent from the brain of DHA‐H‐treated mice. Oral administration of DHA‐H to a transgenic model of AD (5xFAD mice) induces a significative cognitive recovery. However, the molecular mechanism underlying this neuroprotective effect remains largely unresolved.MethodScreening of potential receptors for DHA‐H and HPA was performed using computational tools. PPARG (Peroxisome Proliferator‐Activated Receptor γ) activity was determined by cell‐based assays. Levels of proteins involved in amyloid production as well as synaptic markers were determined by WB and/or ELISA. β‐ and γ‐secretase activities were measured in cell‐free assays. Neuronal density was determined by immunohistochemistry. Brain levels of DHA‐H and HPA were determined by Electrospray Ionization – Mass Spectrometry (ESI‐MS).ResultBoth DHA‐H and HPA are activators of PPARG. We have analyzed the effect of DHA‐H treatment on the amyloidogenic route in the 5xFAD mice and this effect was related with PPARG activity. We observed a modulation of protein levels and enzymatic activities involved in β‐amyloid production as well as a prevention of synaptic and neuron degeneration in DHA‐H‐treated mice as compared with untreated controls. These changes were related with improved cognitive scores in these mice.ConclusionAll these results together indicate that DHA‐H administration must prevent neuronal degeneration and cognitive decline in AD mice through its immediate metabolite HPA and without apparent involvement of PPARG.
Medication utilization among vascular dementia population
Authors: Razavian Narges , Dodson John , Masurkar Arjun V , Wisniewski Thomas , Horwitz Leora , Aphinyanaphongs Yindalon 
Published: December 2021

AbstractBackgroundIt is estimated that up to 40% of Alzheimer’s Disease and Related Dementias cases can be prevented or delayed by addressing modifiable factors including those that influence vascular risk (hypertension, obesity, smoking, physical activity, diabetes). Prevention may be particularly important in the vascular dementia subtypes. Despite the supporting evidence, the rates of medical therapy to reduce vascular risk are not well described.MethodWe assessed the utilization of statins, aspirin, and blood pressure (BP) medications in adults age ≥65 years cared for at NYU Langone Health, as recorded in the electronic health record. We included two cohorts: cohort 1 included patients who were diagnosed with vascular dementia (VaD) at NYU Langone Barlow Center for Memory Evaluation between January 1, 2015 and June 24, 2019. Cohort 2 extended the inclusion to seniors with VD diagnosis by any NYU Langone physician. Definitions for vascular dementia, the covariates assessed, and medications that we included in each category are shown in Tables 1‐3.ResultWe included 419 and 3745 patients in cohort 1 and cohort 2, respectively. Table 4 shows the characteristics and medication adherence in cohorts 1 and 2. In cohort 1, the prescription rates for statins, aspirin, and BP medications were 66%, 66%, 70%. In cohort 2, the rates for statin, aspirin, and BP medications were 56%, 46%, and 65%, respectively. The differences between prescription rates in cohort 1 and 2 for the three medication groups were statistically significant (p<0.05).ConclusionOur analysis of the utilization of cardiovascular medications among patients with vascular dementia illuminates potential gaps both among patients who receive care at specialty clinics, as well as the overall population with vascular dementia. The rates of medication utilization are higher for patients under the care of cognitive neurologists. Electronic health records can help identify large cohorts of patients who may benefit from improved access to preventative measures including cardiovascular medications.
Early onset dementia: Clinical utility of cerebrospinal fluid amyloidβ and tau measures in diagnosing mild cognitive impairment
Authors: Hosseini Akram A. , Brown Thomas , Mannino Luca , Gran Bruno , Junaid Kehinde , Mukaetova‐Ladinska Elizabeta 
Published: December 2021

AbstractBackgroundThe differentiation of a preclinical or prodromal Alzheimer’s disease (AD) is challenging particularly in patients with Early Onset Alzheimer’s or Related Dementias (EOARD). The first clinical symptoms of AD during the prodromal phase are mild cognitive impairment (MCI), with some younger adults presenting with depression or anxiety. We report a local practice on utilising diagnostic lumbar puncture to investigate the cause of MCI for the diagnosis of EOARD at a tertiary neurocognitive referral centre.MethodThe study was approved by the Ethic Committee (Ref:18/EM/0292). 30 participants aged 32‐68 years old at the onset of symptoms (mean 62 years; 61% female) from the Nottingham EOARD clinics (UK) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, radiological features (MRI, FDG‐PET CT) and CSF amyloidβ1‐42/1‐40 (Aβ), total tau and Thr181‐phosphorylated tau measurements. Patients were classified into three groups according to the clinical diagnosis: a)MCI secondary to Alzheimer’s disease as defined by NIA‐AA Research Framework [n=16]. b)Subjective Cognitive impairment, stable impairment in cognitive battery with no evidence of neurodegeneration on neuroimaging or abnormal levels of Amyloidb/tau in the CSF [n=9]. c)Other neurodegenerative conditions [n=5] (Table).ResultIn patients with MCI, the CSF total tau and Thr181‐phosphorylated tau levels showed a non‐linear relationship with age, with an inverse U‐shaped curve reaching the highest level at the age of 55 years, followed by a significant decline in the following decade (Figure). In contrast, the CSF Aβ level decreased in the MCI group, independently of age, and was associated with the neuropsychological measures of memory impairment (p=0.037). In contrast, total and phosphorylated CSF tau levels did not correlate with the cognitive performance measures. Similarly, the principal component analysis confirmed that the clinical diagnosis of Alzheimer’s MCI (as per the NIA‐AA criteria) correlated with the CSF Aβ loss.ConclusionIn Early Onset Alzheimer’s disease, the low levels of CSF Aβ appear to be more sensitive than the total and 181Thr‐phosphorylated tau measures in differentiating Alzheimer’s MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness due to making an earlier diagnosis.
The influence of cognitive reserve on Alzheimer's disease progression
Authors: Garba Asabe E , Grossberg George T , Enard Kimberly R , Jano Fabian J , Roberts Emma N , Marx Charlotte A , Buchanan Paula M 
Published: December 2021

AbstractBackgroundThe incidence and prevalence of Alzheimer’s disease (AD) continues to rise in the growing elderly population putting public health at increased economic, healthcare, and caregiving burdens. The effects of AD pathology on the brain are irreversible, making it hard to determine effective treatment after symptom onset. Primary prevention has been proven to reduce the risk of developing AD later in life. Past research found that cognitive reserve (CR), an individual’s ability to cope with brain changes, impacts AD risk. The buildup of CR over a life span has shown positive cognitive implications. However, the influence that CR has on the rate of AD progression remains to be explored. This study used a survey tool that accounts for all CR proxies to explore this gap.MethodTo quantify CR in the study population of 90 AD participants, the Cognitive Reserve Index questionnaire was used. The Clinical Dementia Rating scale was utilized to stage AD progression. One‐way ANOVA and Independent Samples T‐tests were used to test for differences between the mean CR scores of dementia groups. One‐way ANOVA was also used to test for differences between CR level groups and mean number of days it took to transition from one dementia stage to the next. Multivariable linear regression was utilized to determine the unit change in time associated with an increase in CR score.ResultThere was not a significant difference in mean CR score by dementia group (F = 1.96, p = 0.15). After collapsing the moderate and severe dementia groups to compare to the mild dementia group, there was a significant difference in mean CR score (mild mean (SD) = 131(15.0), moderate/severe mean (SD) = 123(20.6), p = 0.05). After controlling for physical activity, for every unit increase in CR score, the number of days for transitioning from mild to severe dementia increased by 34 days (β = 33.94, 95% CI: 8.07, 59.81, p = 0.01).ConclusionHigher CR was associated with slower AD progression. This indicates that consistent engagement in activities that promote CR buildup over a life span are methods for improving AD and dementia health outcomes.
Improving early recognition of Creutzfeldt‐Jakob disease mimics in clinical practice
Authors: Lazar Evelyn , Porter Amanda , Prusinski Christian C , Dunham S Richard , Lopez‐Chiriboga A Sebastian , Day Gregory S 
Published: December 2021

AbstractBackgroundDiagnostic criteria emphasize the use of real‐time quaking‐induced conversion (RT‐QuIC) assays in cerebrospinal fluid (CSF) to identify patients with rapidly progressive dementia (RPD) due to for Creutzfeldt‐Jakob disease (CJD; CDC Diagnostic Criteria; Oct‐2018). Yet, this test is often performed in specialized centers, leading to delays in return of results. There is a need to leverage clinical features and the results of readily available tests to distinguish patients with CJD from those with other causes (‘CJD mimics’), including patients with potentially treatment‐responsive RPD.MethodPatients with definite (pathology‐confirmed) or probable CJD (clinical features with positive RT‐QuIC) were identified through retrospective review of Mayo Clinic Enterprise (n=91) and Washington University in St. Louis records (n=14; Jan‐2014 to Dec‐2020). Demographic, clinical details and results of common investigations (e.g., neuroimaging, CSF analyses and electroencephalogram) were compared between CJD cases and ‘mimics’ who met clinical criteria for probable CJD but did not have CJD.ResultCJD mimics were diagnosed with autoimmune encephalitis (n=8), neurosarcoidosis (n=1), FTLD/MND (n=1) and unknown dementia (n=1), comprising 11/155 (7%) patients enrolled with RPD at study sites. Median [range] ages‐at‐presentation (65.6 [21.9‐81.5] vs 62.4 [32.8‐76.4] years; p=0.09), % females (51% vs 46%; p>0.99) and symptoms/signs were similar between groups, with the exception of motor complaints (e.g., spasms, focal weakness), which were more common in mimics (11/11 vs 55/105; p<0.01). Electroencephalogram findings did not differ between groups. MRI findings compatible with CJD (i.e., restricted diffusion within deep nuclei/cortical ribbon) predominated in cases (80/105 vs 4/11; p<0.01), while elevations in CSF leukocytes (>5 cells/hpf: 6/11 vs 5/103; p<0.01) and protein >45 mg/dL (10/11 vs 43/103; p<0.01) were more common in mimics. Total‐tau levels >1150 pg/mL (76/84 vs 2/10; p<0.01) and ‘positive’ 14‐3‐3 (67/98 vs 3/10; p=0.03) were frequent in cases. Autoantibodies associated with autoimmune encephalitis were detected in 5/10 mimics but 0/87 cases (p<0.01). Immunosuppressant therapies were provided to 10 mimics and 24 cases, with response limited to mimics.ConclusionsAutoimmune encephalitis, neurosarcoidosis and select neurodegenerative diseases may mimic CJD at presentation. Findings from brain MRI and commonly available CSF tests may facilitate early recognition of mimics, providing an opportunity for early treatment.
Empirical evidence of cognitive change: Calculating reliable change indices for digital tests of cognition in individuals living with Alzheimer’s disease
Authors: Harrison John E , Myers Jennifer Rae , Madero Erica N. , Mak‐McCully Rachel , Gray Michelle , Glenn Jordan M. 
Published: December 2021

AbstractBackgroundThe identification of individuals at risk of progressing from normal health to Mild Cognitive Impairment (MCI) and later to Alzheimer’s disease (AD) has focused recently on using evidence of progressive decline. This approach relies upon employing a reliable metric of cognitive change. One possible approach to this issue involves employing a Reliable Change Index (RCI) methodologyMethodA sample of N = 56 participants were assessed on exams from the Neurotrack assessment suite at baseline and 1‐week later. This assessment is composed of well‐known and previously validated measures of episodic memory, working memory, attention and executive function (see Table 1 for details of tests).ResultsUsing the data from our study cohort we calculated a RCI for each measure using the Jacobson‐Truax method. This requires the determination of a threshold that separates those who are impaired from individuals who are not impaired. It also requires a comparison of an individual’s change from assessment time point 1 and 2 to the standard error of measurement (SEM) of the outcome. RCI and 95% confidence interval (CI) was calculated for each of the Neurotrack tests. By applying the 95% CI to a baseline score, a statistically normal range of later performance can be determined. Values falling outside the CI can be considered evidence of real change.ConclusionsIn this study, we provided individual RCI values and associated CI for each test in the Neurotrack battery. We are currently evaluating the Neurotrack assessment in a longitudinal validation study to investigate sensitivity to change over time.
Characterization of amyloid angiopathy in the retina
Authors: Campbell Melanie C.W. , Emptage Laura , Redekop Rachel , Kitor Monika , Neathway Peter A.C. , Ding Yifan , Hirsch‐Reinshagen Veronica , Hsiung Ging‐Yuek Robin , Mackenzie Ian R. 
Published: December 2021

AbstractBackgroundCerebral amyloid angiopathy (CAA) is a vascular brain disease with risk of severe complications, and high prevalence in those with Alzheimer’s disease (AD). Characteristic amyloid beta deposits in blood vessels in the cerebrum are challenging to diagnose. Amyloid deposits in blood vessels in human retinas have been previously reported. Here, we characterize postmortem, retinal amyloid angiopathy (RAA) in individuals with AD and/or CAA brain pathology. We propose a staging of RAA which could be extended to in vivo imaging, modified from CAA staging in the brain.MethodCorrelation of severity of brain pathology for AD and CAA was assessed for 52 individuals. Formalin fixed retinas from 6 of these individuals were whole‐mounted and stained with thioflavin S and DAPI, then imaged in polarized light and confocal microscopy with 3 florescence channels. While following blood vessels systematically, images of RAA were collected.ResultBrain pathology due to CAA increased in severity with increasing severity of AD pathology as previously reported (Figure 1). RAA was present in all donors with evidence of brain CAA and in two donors with no evidence of brain CAA (Figure 2). Amyloid present in vessels can be imaged dye‐free in polarized light. Our proposed staging of RAA severity is modified from two used in the brain (Figures 3‐6). Stage 1): Amyloid within the vessel and not filling the lumen of the vessel: 1A) Amyloid is not circumferential; 1B) Amyloid is circumferential. Stage 2): Amyloid completely fills the lumen of the vessel. Stage 3): Amyloid both within and touching the outside of the vessel, analogous to dysphoric CAA.ConclusionAmyloid angiopathy in the retina (RAA) may occur concurrently with and potentially prior to brain CAA. Further, severity of RAA could be monitored through the proposed staging which in turn could allow comparison of severities of CAA and RAA. This would elucidate whether RAA severity is a good predictor of CAA severity. Our data confirm the previously reported correlation between brain CAA and AD. Further development of RAA imaging in the living eye may allow earlier and improved diagnosis of brain CAA, facilitating the development and testing of new treatments.