bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic correlates of neuropsychological assessment in behavioral variant frontotemporal dementia
Authors: Matias‐Guiu Jordi A. , Cabrera‐Martín María Nieves , Delgado‐Álvarez Alfonso , Delgado‐Alonso Cristina , Valls‐Carbó Adrián , Moreno‐Ramos Teresa , Carreras José Luis , Pytel Vanesa , Matias‐Guiu Jorge
Published: December 2020

Background

Neuropsychological assessment is an essential tool in the diagnosis and monitoring of patients with neurodegenerative disorders. Cognitive functions underlying neuropsychological tests are complex, and accordingly interpretation is often challenging. In behavioral variant frontotemporal dementia (bvFTD), neural correlates of cognitive testing are largely unknown, and they could be different to other settings such as Alzheimer’s disease (AD). In this study, we aimed to analyze the metabolic underpinnings of neuropsychological test results in a series of patients with bvFTD.

Method

Seventy‐two patients with bv‐FTD according to the consensus criteria were included. Patients were examined with a comprehensive neuropsychological protocol and 18F‐FDG‐PET. Voxel‐based analysis was used to study the correlation between regional brain metabolism and cognitive performance of the following tests: Boston Naming Test (BNT), Trail Making Test (TMT), Rey‐Osterrieth Complex Figure, verbal fluency (semantic and phonological), Free and Cued Selective Reminding Test (FCSRT), Stroop Color Word Interference test, Tower of London, and Visual Object and Space Perception Battery (VOSP). Age, sex, and years of education were introduced as nuisance covariates. A healthy control and Alzheimer’s disease groups were also examined with the same protocol for comparison. Neuroimaging analyses were conducted using SPM12.

Result

Mean age in the bvFTD group was 71.33+/‐7.75 years, and 43 (59.7%) were men. In bvFTD, BNT was positively correlated with the left anterior temporal lobe; FCSRT was correlated with the left frontal cortex; Phonological fluency with left frontal lobe and right superior frontal; semantic fluency with left frontal, temporal and thalamus; TMT‐B was negatively correlated with bilateral medial frontal lobes, especially with the right side; VOSP was correlated with the right frontal lobe.

Conclusion

We showed the brain regions associated to the performance of different standardized neuropsychological tests in bvFTD. The differences observed between bvFTD and AD suggests that neural underpinnings underlying these tests are different according to each disease, confirming the multiple cognitive processes involved during performance of each particular test. Overall, our study provides useful information to achieve a better understanding of neuropsychological examination in patients with bvFTD. In addition, these findings could be useful to detect cognitive subtypes within the syndrome of bvFTD.
TOMM40‐APOE haplotypes are associated with cognitive decline in non‐demented blacks
Authors: Deters Kacie D , Mormino Elizabeth C , Yu Lei , Lutz Michael W , Bennett David A , Barnes Lisa L
Published: December 2020

Background

The poly‐T alleles at the TOMM40‐’523 locus are in linkage disequilibrium with APOE alleles (E3 and E4). However, the pattern of this association varies across race and may influence cognition over time. Contrary to those who identify as non‐Hispanic White, few studies have investigated the role of APOE‐‘523 genotypes in the Black population. Thus, the goal of our study was to investigate the impact of APOE and TOMM40‐‘523 haplotypes on cognitive decline in non‐demented non‐Hispanic Black (NHB) participants, and determine whether effects differ from non‐Hispanic White (NHW) participants.

Method

Distributions of APOE and TOMM40‐‘523 poly‐T alleles were examined across NHB and NHW individuals without dementia at baseline, from three cohort studies of aging and dementia at the Rush Alzheimer’s Disease Center. The impact of zero, one, or two copies of the ’523‐Short (S) variant (poly‐T alleles<20) within APOE genotype on a composite measure of global cognition and five separate domains (global, episodic memory, episodic memory, semantic memory, visuospatial ability, and perceptual speed) derived from 19 individual tests, was examined with linear‐mixed models.

Result

In NHB with E3/E3 (N=294), ‘523‐S/S was associated with faster decline in global cognition, episodic memory, and visuospatial ability (Global: β=‐0.048, p=0.017; Episodic: β=‐0.05, p=0.031; Visuospatial: β=‐0.037, p=0.034) relative to those who did not have a copy of ‘523‐S. In contrast, for NHB E4+ (E3/E4 + E4/E4; N=182), ‘523‐S/S was associated with slower decline in global cognition and visuospatial ability (Global: β=0.047, p=0.042; Visuospatial: β=0.07, p=0.0005) relative to those without ‘523‐S. Further, results indicated a racial difference in E4+ such that NHB with ‘523‐S had a slower rate of decline than NHWs with ‘523‐S. ‘523‐S/S was not statistically different than one copy of ‘523‐S in E3/E3 or E4+ analyses.

Conclusion

Our findings suggest ‘523‐S/S has a different effect on cognitive decline among NHB dependent on APOE allele, and that ‘523 variation may aid in better prediction of early cognitive decline in NHB individuals. Further, racial differences in the effect of E4‐‘523‐S may explain prior mixed findings on E4 and decline in this population.
Incident MCI and dementia in Hispanic and non‐Hispanic whites: Implications for ethnic comparisons of risk in Alzheimer’s Disease Center data
Authors: Salazar Hector , Norton Derek L , Zuelsdorff Megan , Wyman Mary F , Carter Fabu P , Benton Susan Flowers , James Taryn T , Johnson Adrienne L , Lambrou Nickolas H , Cordova Susie Fernandez , Pinzon Maria C Mora , Asthana Sanjay , Gleason Carey E
Published: December 2020

Background

Recruitment strategies have different levels of success in reaching Hispanic populations, potentially introducing bias in large multicenter datasets, such as the National Alzheimer’s Coordinating Center (NACC). The purpose of this study is to examine differences in incident mild cognitive impairment (MCI) and dementia between Hispanic and non‐Hispanic whites.

Method

We included NACC data from 23,963 participants with >1 follow‐up visit. Additional inclusion criteria were: age 60+, did not have Downs syndrome, ethnicity Hispanic or non‐Hispanic, primary race as white, and cognitively normal or diagnosed with MCI at baseline. An event (i.e., conversion) was defined as the first visit/subject age when diagnosed with MCI or Dementia. To compare age‐of‐conversion between Hispanic and non‐Hispanic whites, we used Cox proportional hazard models with variable entry setup. Separate models were fit for baseline cognitive status (MCI vs. normal). Model covariates included sex; educational attainment; baseline diabetes, hypertension, and cardiac event status; referral source; family history of dementia; and primary etiology (for baseline MCI subgroup only). Unadjusted Kaplan‐Meier curves were calculated between Hispanic and White non‐Hispanic subjects for both baseline cognitive strata and outcome (conversion only vs. combined).

Result

Normal cognition Hispanic participants exhibited significant elevated risk of conversion compared to White non‐Hispanic participants (HR=1.316, p=0.005), but risk was non‐significant for the composite event (HR=1.176, p=0.069). For baseline MCI participants, Hispanic ethnicity was significantly associated with reduced risk of both conversion and conversion/death (conversion HR=0.734, p=0.002; conversion/death HR=0.699, p<0.001). In all models, referral sources other than health professional were associated with reduced risk of event. Family history of dementia was associated with increased risk of conversion and conversion/death for those with normal baseline cognition (conversion HR=1.216, p<0.001; conversion/death HR=1.084, p=0.048), but not for those with baseline MCI.

Conclusion

White participants with MCI, referred by clinicians exhibited greater likelihood of disease progression. These data suggest that Hispanic and non‐Hispanic whites in NACC may not be comparable. Therefore, caution should be exercised when interpreting analyses of data examining ethnic differences in incident MCI and dementia.
Alzheimer's disease: Donepezil effects on cholesterol and oxysterol plasma levels
Authors: Costa Alana Caroline , Joaquim Helena Passarelli Giroud , Nunes Valeria Sutti , Kerr Daniel S. , Forlenza Orestes Vicente , Gattaz Wagner Farid , Talib Leda Leme
Published: December 2020

Background

Cholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer's disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)‐hydroxycholesterol (24OHC) which can be driven through the blood‐brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)‐hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short‐ and long‐term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers.

Method

The sample comprised 30 patients with mild or moderate AD and 33 physically and cognitively healthy elderly controls. In the last 6 months prior to enrolment in the study, patients and the control group did not use AChEi or other drugs. After the completion of baseline assessments, all patients were started on donepezil treatment (5 mg/day). Doses were administered orally and increased to 10 mg/day after 1 month. Patients were monitored monthly, the MMSE was evaluated after 3 and 6 months, and CAMCOG was evaluated 6 months after donepezil treatment. Plasma cholesterol concentrations were measured using commercially available enzymatic–colorimetric methods. Measurements of oxysterols (24‐hydroxycholesterol and 27‐hydroxycholesterol) were performed by gas chromatography–mass spectrometry.

Result

At baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC.

Conclusion

These results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer's disease.
Causal communication between gut microbiota dysbiosis and neuroinflammation in Alzheimer’s disease and therapeutic intervention by oligomannate
Authors: Geng Meiyu
Published: December 2020

Background

Recently, increasing evidence has demonstrated the dynamic interaction between gut microbiota dysbiosis and Alzheimer’s disease (AD) progression, yet major knowledge on how gut microbiota pathogenic attacks AD remains obscure.

Method

We provide a multi‐dimensional profiling of gut microbiota, metabolomics and peripheral and central immune patterns in AD transgenic mice, to decipher the pathogenic outcomes of gut microbiota dysbiosis and its potential mechanistic linkage to neuroinflammation in AD progression.

Result

We discovered that, during AD progression, the dynamic alteration of gut microbiota composition and associated metabolites profoundly affected the peripheral immune pattern of the gut and that of the brain. Furthermore, the brain‐infiltrated peripheral immune cells crossed with the microglia activation, contributing to AD‐associated neuroinflammation and then neuronal injury. Importantly, similar alteration in microbiota‐derived metabolites and immune cell subtypes in the blood were also observed in the cohorts of patients with mild cognitive impairment (MCI) due to AD and AD. Interestingly, sodium oligomannate that has demonstrated a consistent cognition improvement in a phase 3 clinical trial in China and approved for the treatment of mild‐to‐moderate AD, was found to suppress gut microbiota dysbiosis and the associated abnormal metabolites, which harnessed peripheral inflammation and neuroinflammation and reversed the cognition impairment in AD transgenic mice.

Conclusion

Our findings highlight the role of gut microbiota dysbiosis‐promoted neuroinflammation and neurodegeneration in AD progression, and further suggest a novel strategy for AD therapy by targeting gut‐brain axis.
Lifetime endogenous estrogen exposure in women influences risk of dementia
Authors: Panizzon Matthew S. , Sundermann Erin E , Jacobs Emily Goard , Karlsson Ida , Pedersen Nancy L. , Gatz Margaret
Published: December 2020

Background

The female reproductive period – menarche to menopause – can serve as a proxy for lifetime endogenous estrogen exposure. A foreshortened reproductive period, either naturally or secondary to medical intervention, has been associated with an increased risk of Alzheimer’s disease (AD), supporting the hypothesis that estrogen exposure is neuroprotective. Prior studies have been limited by small sample sizes, and confounding effects of exogenous hormone exposure (e.g., oral contraception or hormone replacement therapy). In the present study, we examined the association between the length of the reproductive period and dementia in a large, population‐based sample of exogenous hormone naïve women from the Swedish Twin Registry (STR).

Method

Participants were 7,630 women who provided self‐reported health and reproductive history data as part of the Screening Across the Lifespan Twin (SALT) project. Subsequent dementia diagnoses were obtained through follow‐up studies that leveraged either in‐house clinical assessments or national health registry data. Mixed effects logistic regression models examined the effect of length of the reproductive period on all‐cause dementia and AD diagnoses while controlling for the non‐independence of the twin data. Analyses controlled for birth year, number of pregnancies, and history of surgical menopause (i.e., oophorectomy).

Result

The prevalence of all‐cause dementia and AD within the sample was 15.2% and 7.7%, respectively. The mean age at participation in SALT was 65.6 years (SD=9.9), and mean age at dementia diagnosis was 83.4 (SD=7.3). Reproductive span averaged 35.4 years (SD=5.2), and 7.4% of the sample reported surgical menopause. Shorter reproductive span was significantly related to increased likelihood of all‐cause dementia (p=.0008) and AD (p=.0012). Relationships were non‐linear, such that the added benefit of longer reproductive span on dementia/AD risk waned within the higher range of reproductive span. Premature menopause (prior to age 40), significantly increased likelihood of all‐cause dementia (OR=1.42 (1.02‐1.99) but not of AD (OR=1.38 (0.88‐2.17). Number of pregnancies and history of oophorectomy were not significant predictors.

Conclusion

These results demonstrate that endogenous estrogen exposure in women is indeed a significant predictor of all‐cause dementia and AD, lending support to an endocrine‐related mechanism that may contribute to sex differences in AD risk.
Assessment of emerging mobile connected technologies to promote outdoor mobility and transit in older adults and in those with Alzheimer’s disease and related dementias: Usability, stressors, barriers, and implications for policy
Authors: Zanwar Preeti , Lee Chanam , Ham Youngjib , Chaspari Theodora , Kim Jinwoo , Tan Shuman , Manser Michael , Ahn Changbum
Published: December 2020

Background

Population aging is known to increase the risk of Alzheimer’s Disease (AD) and AD‐Related Dementias (ADRD). A majority of older adults and those with ADRD prefer to age within their neighborhoods. Maintenance of mobility is important for both older adults and in those with ADRD to sustain independence and to promote quality‐of‐life. However, changes in mobility patterns outside of home can create physical and emotional distress due to infrastructure barriers and lack of accessible transportation.

Method

Our overall approach will synthesize learnings from literature review on (1a) commercial technologies that collect, monitor, visualize and analyze data on mobility patterns; (1b) research advances on algorithm developments for mobility, disease pattern detection and prediction and from (2) summary of focused interviews from field experts in several domains: transit technologies, urban planning, assistive technology partners, healthy aging and community environments, and from gerontologists with expertise in dementia care.

Result

The paper aims to understand the how, when, where, and why of walking and travel needs, current barriers, and how technologies can overcome challenges and support healthy aging in community environments and foster dementia‐friendly transportation for older adults and for those with ADRD. The paper aims to review (1) commercial technologies and research advances that can monitor outdoor physical activities (e.g. wearable technologies including wristband type sensors, inertial measurement units, and smartphone to collect physiological responses for electrodermal activity, heart rate, gait patterns, and body balances), (2) stressors and barriers in senior living community environments and the source of physical and emotional distress (e.g. Computer Vision techniques), and (3) mobile transportation technologies (e.g. MEILI, rMove, Itinerum, PEACOX, SmartMo, GPS‐ATD, Future Mobility Sensing, MMMonitor) that allow the understanding of everyday independent mobility patterns and transport needs for older adults, for those with AD+ADRD and their caregivers.

Conclusion

Understanding of mobility patterns and visual appearance of neighborhoods for older adults and for cognitively challenged may aid in the creation of stressor and barrier‐free environments; a pre‐requisite to promote mobility, independence, and for constructing a digital twin city (DTC) model for age‐friendly and dementia friendly transit‐communities.
How does what study partners report differ based on their relationship to the primary subject?
Authors: Stites Shana D , Largent Emily A , Gill Jeanine , Harkins Kristin , Karlawish Jason
Published: December 2020

Background

Studies of persons with Alzheimer’s disease (AD) and related dementias typically require “study partners” (SPs) to report on the subject’s wellbeing and function. But little is known about how who a SP is might impact on these reports. Knowing this may help inform the interpretation of AD research.

Methods

We analyzed data from 730 older adults and their SPs enrolled in the Aging, Demographics and Memory Study (ADAMS). SPs provided data on their assessment of subjects’ functioning through the following: (1) the Blessed Dementia Rating Scale (BDRS), a multi‐domain informant measure of functional capacity; (2) three single‐item ratings of the subject’s “memory at the present time,” ability “in making judgments and decisions,” and ability to “organize his/her daily activities”; (3) instrumental/basic activities of daily living (IADL/BADL) scales. Subject cognition was assessed in an independent neuropsychological assessment using the mini‐mental status exam (MMSE), Trails A/B, Serial 7s, Boston Naming, and Animal Fluency. Bivariate and multivariable regression analyses were used to examine differences in SP reports based on their relationship to the subject. Demographics of SPs and subjects were also analyzed.

Results

Of SPs, 34.9% (n=255) were spouses, 38.4% (n=281) were adult children, and 26.6% (n=194) had a different relationship to the subject. In bivariate models, adult children were more likely to be college educated and provide care to the subject than spouses. In bivariate analyses, adult children rated subjects as more impaired on the BDRS and single‐item measures of memory, judgment and organizational abilities than did spouses(p<0.05). In multivariable analyses that controlled for differences in cognitive and functional performances, adult children, on average, rated subjects as less impaired on measures of memory, judgment, and organizational abilities than spouses(p<0.05). But, reporting varied in subgroups; in cognitively unimpaired subjects (MMSE>28), only 63.0% of child SPs reported a BDRS that indicated lack of impairment while 90.8% of spousal SPs did so (p<0.05).

Conclusions

Spouses and adult children are similarly likely to serve as SPs, but there are differences in how they report on subject functioning. Our findings have important implications for interpreting informant reports, particularly, of persons with no or mild cognitive impairment.
Klüver‐Bucy syndrome due to stroke in the left temporal lobe
Authors: Canella Marcelo , Baptista Rafael Mazzini , de Oliveira Fabricio Ferreira , Bertolucci Paulo Henrique Ferreira
Published: December 2020

Background

Klüver‐Bucy syndrome (KBS) comprises: 1) hyperorality, 2) hypermetamorphosis, 3) hypersexuality, 4) eating disorder, 5) placidity, 6) visual agnosia (psychic blindness) and 7) amnesia (at least three components are described as partial KBS). The classic description involves bilateral injuries to the anterior temporal lobes, but it has been reported that unilateral lesions can also lead to KBS.

Method

Case report and analyses of MR Images (T1, Flair and Tractography) of a patient presenting partial KBS due to stroke in the left temporal lobe.

Result

Male patient, 69 years‐old, with cognitive deficits that have begun after a left frontotemporal stroke in 2003, with remarkable changes in the temporal pole. In the first months after the stroke, he used to get lost when out of home and had difficulty remembering names and recognizing well known persons due to psychic blindness. During the next years, the patient developed impairment in declarative memory, but preserved visuospatial skills (many times coming to the medical appointments alone, using public transportation). Over time, he developed binge eating (once eating 1 kilogram of cheese, for instance), inability to deal with money (unnecessary loans in banks) and bizarre sexual behavior (such as excessive addiction to porn movies, public masturbation, flirting with women in his neighborhood, and an episode of inappropriate sexual behavior with his daughter‐in‐law). The patient still resists taking bath and changing clothes.

Conclusion

The exact anatomic basis of KBS is still controversial. What is remarkable is the main role of the amygdala in the syndrome. However, periamygdalar lesions can cause disconnection syndromes and damage the limbic network that involves the uncus, the hippocampus, the insular cortex, orbitofrontal and cingulate gyri. Patients with KBS can mimic behavioral variant frontotemporal lobar degeneration (bvFTLD) – particularly regarding eating and sexual disorders, probably due to the connections between the amygdala and the orbitofrontal gyri. The integrity of these two regions and their connections probably play an important role in emotional continence, modulating basic desires in the human species. Lesions in the uncinate fasciculus can predispose to KBS. Our patient exhibits lack of fibers connecting temporal lobe and orbitofrontal cortex showed in the tractography.
A meta‐analysis of neurocognition in mild cognitive impairment in Parkinson’s disease and progression to Parkinson’s disease dementia
Authors: Wallace Elizabeth , Balthrop Kullen , Harp Jordan , Segerstrom Suzanne , van Horne Craig , Koehl Lisa , Schmitt Frederick A.
Published: December 2020

Background

Parkinson’s disease (PD) is a neurodegenerative condition resulting in characteristic motor impairments and cognitive changes, including executive functioning (EF) deficits. These cognitive changes worsen for the approximately 30% who develop Parkinson’s disease dementia (PDD). Mild cognitive impairment (MCI) is a transitional state between normal cognition and dementia. Although PD‐MCI and its neurocognitive correlates have been increasingly studied as an indicator of risk for PDD, the typical PD‐MCI neurocognitive profile remains undefined. The present meta‐analysis examined cross‐sectional studies administering neuropsychological testing to PD‐MCI and cognitively normal PD to provide aggregated effect sizes of group test performance by neurocognitive domain. Longitudinal studies examining PD‐MCI to PDD progression were subsequently meta‐analyzed.

Method

Data were coded from 92 cross‐sectional papers for PD‐MCI vs. cognitively normal PD groups. Data were coded from five longitudinal papers for PD‐MCI converting to PDD vs. PD‐MCI not converting to PDD. Random effects meta‐analytic models were conducted to provide aggregated weighted effect sizes (Hedges’ g), indicating the difference between these groups in their respective analyses.

Result

Cross‐sectional results indicate that overall cognitive measures produced a large effect size (g = 1.07, 95% CI [0.99, 1.14], p < .05) with tests of visual delayed memory producing the largest effect size (g = 1.90, 95% CI [1.03, 2.77], p < .05). Longitudinal results indicate that overall cognitive measures produced a medium effect size (g = 0.48, 95% CI [0.41, 0.55], p < .05) with tests of executive functioning producing the largest effect size (g = 0.70, 95% CI [0.51, 0.89], p < .05).

Conclusion

Results of the first PD‐MCI meta‐analysis indicate that, across cross‐sectional and longitudinal studies, measures of cognitive performance have value in differentiating PD‐MCI from cognitively normal PD and PD‐MCI and PDD. Within cross‐sectional studies, tests of visual delayed memory produced the largest effect size, with group performance differing by approximately two standard deviations. This result may further reflect EF deficits common in PD, as well as a temporally mediated process classically more characteristic of other dementia syndromes. Longitudinal results further highlight the importance of EF changes in progressing PD and suggest power to predict progression to PDD.
Clinical versus neuropathological diagnosis in an ADRC sample: Factors impacting diagnostic concordance rates
Authors: Neugroschl Judith , Sewell Margaret , Haas Mikayla , Radler Keith , Purohit Dushyant , Grossman Hillel , Zhu Carolyn W. , Sano Mary
Published: December 2020

Background

Improving clinical diagnostic accuracy and refining criteria is challenging in dementia research. To explore our ADRC’s diagnostic accuracy, a QI project was initiated to identify potential systemic areas affecting our center’s performance.

Method

Clinical consensus diagnoses were compared to the neuropathological findings of 68 ADRC brain bank participants between 2008‐2017. Concordance level (full, partial, discordant) was assigned by three authors (MS, JN, and HG) with input from our neuropathologist (DP). Fisher's exact test was used to examine concordance and Clinical Dementia Rating (CDR), race, age at death, education, number of visits, time between last visit and death, onset age, and depression.

Results

Participants were 56% female, 88% non‐Hispanic white, education 14.6+/3.9 (range 2‐22), age of onset 71+/‐11 (range 47‐93), age at death 82.5+/‐10.4 (range 52‐102), CDR sum of boxes 12.8+/‐6.5, CDR Global 2.2+/‐1.03, number of follow‐up visits 2.5+/‐2.8, one visit only 40%, 56% had a visit within 18 months before death ( range 0‐132 months). Depression was present in 28%. Primary clinical diagnosis at death was 82.4% AD, 7.4% normal, 4.4% MCI, 2.9% DLB and 3% other. 88% were fully or partially concordant (clinical diagnosis matched at least one neuropathological diagnosis). Of the 8 discordant cases, 2 had no identifiable neuropathology despite dementia; 2 had tauopathies; 1 was an AD/FTD mismatch. Three who were >92yo had no clinical diagnosis but exhibited AD pathology. For partially concordant cases where the second diagnosis was mismatched, it was most frequently DLB (80%). Concordance rate was not associated with any of the above clinical/demographic variables except for CDR and race (p < 0.05). Regarding CDR, 5/8 (63%) discordant cases had a CDR of 0.5 (mild symptoms); the other three had a CDR of 3 (severe dementia). 3/8 minority cases were discordant but two had diagnoses currently only available at autopsy.

Conclusion

Consistent with the literature, the most common error was either missing DLB when present or diagnosing it when absent. No systemic issues were identified that contributed to inaccuracies.
Mild behavioral impairment checklist differentiates normal controls and MCI in a well‐characterized sample
Authors: Sewell Margaret , Neugroschl Judith , Zhu Carolyn W. , Krystal Hannah , Thepmankorn Parisa , Velasco Nelly , Martin Jane , Sano Mary
Published: December 2020

Background

Neuropsychiatric symptoms (NPS) are common early signs of cognitive impairment and dementia. The Mild Behavioral Impairment (MBI) Checklist was created to capture these symptoms. Our objective was to use the MBI to measure NPS in non‐demented normal and MCI research participants and to identify associations among MBI and other established clinical and demographic measures.

Methods

ADRC participants with MCI (N=52) or NC (N=84) completed the MBI. The MBI’s 34 yes/no questions assess decreased motivation, emotional dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. ‘Yes’ answers were ranked in severity on a Likert scale of 1 (Mild) to 3 (Significant). Responses were summarized to create global (range 0‐102, with lower scores representing fewer symptoms) and domain scores which were compared in MCI/NC groups. Correlations were run by diagnostic group for the MBI and the demographic and clinical variables. Multivariable regression models examined the relationship between MBI total and diagnosis after controlling for participant characteristics.

Results

The characteristics of our total sample were: (mean±SD) age=76.6±8.2, 64% female, 56.4% non‐Hispanic white, 26.3% Hispanic,17.3% non‐Hispanic black, and education 15.3±4.1 years. As regards demographics, there were no statistical differences between NC and MCI. In the MCI group, the MOCA (lower), GDS, NPIQ, FAQ (higher) were all significantly different from the NC group (all p<0.05). MBI total was significantly higher in the MCI group (mean MCI 11.7±15.9, NC 5.2±8.0 p<0.001). MBI domain scores were significantly higher as well (all p<0.01) except for impulse control (p=0.07). For both the MCI and NC groups, MBI‐total was significantly negatively correlated with education and positively with depression in the past 2 years as well as current GDS (all p<0.05). In multivariate regression analyses these significant associations remained.

Conclusion

Controlling for demographic factors and comorbidities, MBI scores are significantly different between normal controls and those with MCI.
NIA genetics of Alzheimer’s disease data storage site (NIAGADS): Update 2020
Authors: Vogel Briana , Kuzma Amanda B. , Valladares Otto , Greenfest‐Allen Emily , Klamann Conor , Issen Heather , Gangadharan Prabhakaran , Katanic Zivadin , Zhao Yi , Qu Liming , Lin Han‐Jen , Moon Michelle K. , Leung Yuk Yee , Naj Adam C. , Stoeckert Christian J. , Schellenberg Gerard D. , Wang Li‐San
Published: December 2020

Background

NIAGADS is a national genetics data repository that facilitates access of genotypic data to qualified investigators for the study of the genetics of late‐onset Alzheimer’s disease (AD) and other neurological diseases. Collaborations with large consortia and centers such as the Alzheimer’s Disease Genetics Consortium (ADGC), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Alzheimer’s Disease Genome Sequencing Project (ADSP), and the Genome Center for Alzheimer’s Disease (GCAD) allow NIAGADS to lead the effort in managing large AD datasets that can be easily accessed by the research community and utilized to their fullest extent.

Method

NIAGADS is supported by National Institute on Aging (NIA) under a cooperative agreement (U24 AG041689). All data derived from NIA funded AD genetics studies are expected to be deposited in NIAGADS or another NIA approved site. NIAGADS manages a Data Sharing Service (DSS) that facilitates the deposition and sharing of genomic data and association results with approved users in the neurodegenerative research community. In addition, researchers are able to freely use the NIAGADS Genomics Database to search annotation resources that link published AD studies to AD‐relevant sequence features and genome‐wide annotations.

Result

As of January 2020, NIAGADS houses 67 datasets (23 added in 2019) with >59,000 samples and nearly 34 billion genotypes. Qualified investigators can retrieve ADSP sequencing data with ease and flexibility through the NIAGADS DSS. The ADSP and other contributing studies have completed whole exome sequencing (WES) of 20,630 subjects and whole‐genome sequencing (WGS) of 4,750 subjects. Raw WES and WGS files, quality controlled VCF files, and phenotype data files are available via qualified access. The next planned dataset release will occur in late 2020 and will contain an additional 13,136 genomes jointly genotype called with the first release of 4,750 genomes, totaling about 17,886 genomes.

Conclusion

NIAGADS is a rich resource for AD researchers, with the goal of facilitating advances in Alzheimer’s genetics research. By housing datasets from multiple projects and institutions, NIAGADS enables AD researchers to be more efficient in meeting their research goals. Datasets, guidelines, and new features are available on our website at https://www.niagads.org.
A newly developed amnestic subjective cognitive decline questionnaire shows high internal consistency and inter‐rater reliability
Authors: Flores‐Vazquez Juan Francisco , Acosta‐Castillo Gilberto Isaac , Contreras‐López José Juan , Cruz‐Contreras Cecilia , Aleman André , Enriquez‐Geppert Stefanie , Sosa‐Ortíz Ana Luisa
Published: December 2020

Background

Subjective cognitive decline (SCD) represents a state in which a participant perceives a decline in cognitive functions, yet standardized psychological tests remain within expected performance compared to age‐ and education‐matched controls. SCD is growingly recognized as a risk state for mild cognitive decline (MCI), and eventually, dementia. In this study, we introduce a newly developed Amnestic Subjective Cognitive Decline questionnaire (aSCDq), an instrument with four screening and five severity items (Table 1). We present preliminary internal consistency and inter‐rater reliability results.

Method

We analyzed the clinimetric data from 52 older adults (age 67.2 ±4.4 years), 9 diagnosed with amnestic Mild Cognitive Impairment (MCI), 16 with amnestic Subjective Cognitive Decline (aSCD), and 27 healthy older adults (HOA). We used polychoric correlation matrixes in a principal component analysis to assess the internal consistency of the four screening items, and to analyze the correlation between subject and informant response in all items.

Result

High internal consistency was found regarding the four screening items, resulting in a single component with an eigenvalue of 3.3, and 0.83 explained variance. High inter‐rater correlations in all screening items were found (1: 0.9, 2: 0.8, 3: 0.5, 4: 0.7), with more variable correlations demonstrated in severity items (s1: 0.3, s2: 0.5, s3: 0.7, s4: 0.9, s5: 0.6). Higher scores (i.e. worst memory complaints) were consistently reported by subjects in HOA and aSCD groups, and by informants in the MCI group.

Conclusion

Based on these preliminary results, the aSCDq has been shown to be a consistent and reliable tool to determine aSCD in older adults. The inter‐rater differences are slight but consistent with previous literature. For a full validation of this instrument, a higher number of participants will be necessary.
Baseline cognitive assessment in the Life After 90 Study: A racially/ethnically diverse cohort of people age 90 and older
Authors: Petrosyan Diana , Demos Asmeret , Ganzon Czarina , Popovich Oksana , Gaied Reham , Johal Sharan , Corrada Maria M.M. , Kawas Claudia H. , Whitmer Rachel A. , DeCarli Charles
Published: December 2020

Background

The prevalence of Alzheimer’s disease and related disorders increase with age and is particularly high among the growing segment of oldest‐old (≥90 years). Despite considerable research in this area, a significant gap still exists in the epidemiology of these diseases among ethnic minorities.

The LifeAfter90 Study is an ongoing prospective study of long‐term members of Kaiser Permanente Northern California Health Care System (KPNC) older than 90 without a diagnosis of dementia in their medical records. The study aims to explore racial differences in the incidence of cognitive impairment, identify its determinants, and understand the pattern of brain pathologies in an oldest old population of Blacks, Asians, Hispanics and Whites (enrollment goal=800). This abstract presents descriptive analyses of the first 383 participants enrolled.

Method

Participants receive clinical assessments every 6 months including collection of health history, physical and neurological examination, Clinical Dementia Rating Scale (CDR), Modified Mini‐Mental State Exam (3MS), Functional Activities Questionnaire (FAQ) and Short Physical Performance Battery (SPPB).

Result

Most individuals had normal cognition (55.4%), were female (63.4%) and white (42.3%) at a mean age of 93.6 years at enrollment (Table). Participants reported their health as generally good, although 11% had dementia at initial evaluation. Individuals with dementia were significantly older. No association was identified between race/ethnicity and cognitive status. Higher education (≥high school diploma) was more common among the normal cognition (NC) group. Participants with mild cognitive impairment and dementia had significantly lower SBBP scores (5.7 and 3.7 respectively) compared to people with NC (6.8). Functional scores due to cognitive difficulties showed the same trend across level of cognitive ability. Surprisingly, vascular disease was more prevalent among individuals with NC (Table). Logistic regression analysis that included age, race/ethnicity, gender, education and SPPB scores, found a high sensitivity and specificity for dementia (ROC=0.96) based on 3MS and cognitive FAQ (Figure).

Conclusion

The oldest old are a select group of the growing population who may escape major illnesses or delay their onset toward the end of life. Preliminary analysis of this population identifies discrepancies of great importance to be further explored once the enrollment is completed.
The FNAME yields equivalent results differentiating amnestic mild cognitive impairment from subjective cognitive decline and healthy controls in Mexico and the Netherlands
Authors: Flores‐Vazquez Juan Francisco , Van der Kolk Iris , Contreras‐López José Juan , Cruz‐Contreras Cecilia , Stegeman Rutger A. , del Pilar Andrés‐Benito María , Acosta‐Castillo Gilberto Isaac , Aleman André , Sosa‐Ortíz Ana Luisa , Enriquez‐Geppert Stefanie
Published: December 2020

Background

The Face‐Name Associative Memory Exam (FNAME) has been shown to detect memory deficits early in the spectrum of Alzheimer’s disease. In this study, we used a newly developed and further extended version of the FNAME, to evaluate the discriminating ability of this test in amnestic cognitive decline (aMCI), amnestic subjective cognitive decline (aSMD), and healthy controls (HC) in two different cultures, namely Mexico and the Netherlands.

Method

Participants were recruited in two sites, in Mexico (n= 69) and the Netherlands (n= 55). The mean age of the subjects was 69.3 ±6 years, and the mean years of education 15.5 ±5 years. In this study we used a newly extended version of the FNAME that was developed in both countries concurrently. A total of 42 aMCI, 43 aSCD, and 32 HC were assessed. We used a mixed model ANOVA, with the factors FNAME (7 subtests), GROUPS (aMCI, aSCD, HC), and the SITES (Mexico, the Netherlands) and post hoc t‐tests.

Result

Crucially, a high interaction of FNAME x GROUPS was revealed. Subsequent t–tests showed that the FNAME was able to detect differences between aMCI and aSCD/HC. No significant differences were observed between aSCD and HC. The three‐way interaction’s effect was non‐significant (F= 1.7, p= 0.07). As expected, we found a significant main effect of FNAME (F= 228.4, p< 0.001) demonstrating differences of demands of the subtests (e.g., recall, recognition), as well as a main effect of GROUPS (F= 2.1, p= 0.02). A two‐way interaction of FNAME x SITES was similarly revealed (F= 2.95, p< 0.001), reflecting a difference regarding the performance between sites.

Conclusion

This newly adapted and extended version of the FNAME test is able to differentiate aMCI subjects from aSCD and EC both in Mexico and in the Netherlands. Further studies should focus on better understanding the differences in performance in these countries.
Integrity of the blood‐brain barrier and changes in the microvasculature during the progression of Alzheimer’s disease in the 3XTG‐AD model
Authors: Islas‐Hernandez Azul , Garcia‐Delatorre Paola
Published: December 2020

Background

There is evidence that vasculature failures are related with the development of Alzheimer´s. Between 60 and 90% of patients with AD present with pathologies of cerebrovascular disease. The blood brain barrier (BBB) is a highly selective, semipermeable chemical and structural barrier that ensures a stable internal environment in the brain. BBB dysfunction was initially identified in animal models for AD, and confirmed in patients. To date it is not clear how it originates. Physically, BBB endothelial cells are bound by tight junction complexes (TJ), formed by plasma membrane proteins, such as ocludins and claudins and cytoplasmic scaffolding proteins, such as ZO1. The study of changes in the expression of TJ proteins in a 3xTg‐AD mouse model at different ages will allow us to determine if damage to the BBB occurs before the appearance of amyloid‐β plaques.

Method

The animal's brain (3xTg‐AD mice of 9 and 13 months) is removed. Subsequently, the microvasculature is precipitated by density‐dependent centrifugation through the use of a solution with dextran, managing to separate the cerebral parenchyma and the myelin from the microvasculature. Once the microvessels are obtained, we incubate with anti‐ZO‐1, claudin‐5 and ocludin fluorescent primary antibodies and secondary antibodies (Alexas 488 and 546) and Hoechst 33342. Isolated microvessels are mixed with a fluorescent mounting medium (Fluoromount), mounted on slides and covered with a coverslip. Once mounted, they are scanned with a confocal laser scanning microscope.

Result

We found a decrease in the expression of tight junction proteins in 3xTg‐AD mice of 13 months compared to the same model but at 9 months and also compared to control animals. Morphological differences were also observed in the microvessels of the animals 3xTg‐AD in comparison with the WT and between the animals of 9 and 13 months, with morphological damage being more evident in the older animals.

Conclusion

This could be telling us that the BBB is compromised. We still have to analyze the association between this decrease in TJ proteins and the accumulation of beta‐amyloid, in addition to analyzing it at earlier ages in order to establish from what age these changes in this murine model are measurable.
Pain and behavioral subgroups among nursing home patients with worsening cognition: A latent transition analysis
Authors: Forrester Sarah N. , Jesdale William , Morrison Reynolds , Lapane Kate L.
Published: December 2020

Background

Prevalence estimates of pain in nursing home patients with dementia range from 40% ‐ 60% however pain among those who have difficulty with self‐report such as those with dementia is often missed. Pain scales may miss some key indicators of pain such as aggressive behavior (physical and verbal) and rejection of care, particularly among those who have cognitive difficulties. The purpose of this study was to utilize measurements of staff‐assessed pain, agitated and reactive behavior, functional status, and symptoms of depression to uncover non‐traditional pain subgroups.

Method

The Minimum Data Set 3.0 contains information on the health and functional status of every nursing home resident in Medicare/Medicaid certified nursing homes in the United States. Only patients who had staff assessed pain at admittance, 3 months, and 6 months, and thus were unable to self‐report pain, were included in the analysis (n = 26,816). Latent class analysis was used first to classify subgroups of pain, depression, functional status, and behavioral symptoms and then latent transition analysis was used to measure if and how patients moved between these subgroups at 3 and 6 months given if their cognition (measured by the Cognitive Performance Scale) got worse or had no change/got better.

Result

The latent class analysis revealed 5 classes: behavioral plus depression, functional, physical, behavioral, and low classes. At all time‐points the functional class was the most prevalent (∼28%) and the behavioral plus severe depression was the least prevalent (∼8%). Among those with worsening cognition, pain manifesting as behavioral symptoms in addition to depression remained largely unchanged in the first three months but partially transitioned to a subgroup characterized by physical dependence or remained the same by 6 months. Among the same group, pain manifesting as behavioral symptoms without depression largely stayed the same from admittance to month 3 with some movement to the behavioral plus depression and physical subgroups and largely stayed in the behavioral class by month 6.

Conclusion

This may indicate that pain manifesting as behavioral symptoms is not being properly treated among those with worsening cognitive function.
Aβ‐potentiated and Aβ‐independent age‐related opacity changes in the lens of the eye in wild‐type and APPswe transgenic mice
Authors: Moncaster Juliet A. , Minaeva Olga , Goldstein Lee E.
Published: December 2020

Background

The lens of the eye is composed of crystallin proteins. These proteins have been shown to interact with Aβ in particular in Alzheimer’s disease. Crystallin proteins undergo various post‐translational modifications during aging that disrupt the normal functioning of these proteins resulting in protein aggregation and light scattering. We expand on our previous work and investigated here the aging effect on lens opacity in an Aβ‐independent (wild‐type mice) and Aβ‐potentiated (Alzheimer’s disease transgenic mice [APPswe]) environment.

Method

Mice were bred, maintained and genotyped at Boston University. Mice were sacrificed at ages 8‐35 months, perfused with phosphate buffer saline, lenses were isolated and imaged under two different sources of light using a D70 digital Nikon camera and a Zeiss stereophotomicroscope.

Result

Wild‐type aged mice demonstrated light scattering and opacities in two distinct regions of the lens in aged mice compared to younger mice. Moreover, APPswe aged mice showed increased scattering in the outer layer compared to wild‐type aged mice.

Conclusion

Two distinct light scattering regions of the lens are affected during aging involving Aβ‐potentiated mechanisms in APPswe mice and Aβ‐independent mechanisms in wild‐type mice.