bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing flortaucipir tau‐PET deposition patterns across the Alzheimer’s disease spectrum: A comparison between regional and whole‐brain approaches
Authors: Chapleau Marianne
Published: December 2021

Background

The pattern of tau‐PET deposition might not always follow the classical post‐mortem Braak stages (Vogel et al, 2020). Yet, most current studies use a temporal meta‐ROI to calculate tau‐PET abnormality. We assessed inter‐individual patterns of tau binding across the spectrum of late‐onset Alzheimer’s disease (AD). We computed a score representing the spatial extent uptake of tau‐PET and compared it to a classical temporal meta‐ROI.

Method

We selected 766 ADNI participants along the AD spectrum (controls [CN], early mild cognitive impairment [eMCI], late MCI [lMCI] and AD patients) who underwent flortaucipir tau‐PET and had an available beta‐amyloid (Aβ)status (Table 1). We fitted 2‐distribution Gaussian mixture‐models to calculate thresholds of liberal and conservative tau retention (50% and 90% probability to be in the high SUVR distribution, respectively) in the classical Braak stages and all 70 FreeSurfer brain regions. Using this categorization, we defined positivity in the different Braak stages (Figure 1A‐C) and individual regions (Figure 1B‐D). We calculated a fine‐grained measure of spatial extent by summing the number of regions showing tau abnormality (Figure 1D and 2A). We also computed a temporal meta‐ROI SUVR (Figure 2B, Jack et al, 2018 regions).

Result

In Aβ‐positive participants 14% CN, 44% eMCI and 78% lMCI‐AD had elevated SUVRs in Braak stage 1 using the conservative threshold (Figure 1C, yellow). Participants who progressed to subsequent Braak stage(s), defined with conservative thresholds, were positive on all previous stages using a liberal or conservative threshold (Figure 1C yellow and green, 99% of the sample). Only the spatial extent of tau deposition was associated with worse cognition in CN individuals (Figure 3). In AD patients, both greater spatial extent of tau deposition and higher temporal meta‐ROI SUVR were associated with lower cognition, with the spatial extent index showing stronger associations (Figure 3). In AD, further widespread spatial extent and temporal binding was associated with younger age (Figure 4).

Conclusion

In a typical amnestic cohort of late‐onset AD,the pattern of tau deposition follows the traditional Braak stages. Using a spatial extent index provides stronger results than a temporal‐meta ROI index in detecting associations with cognition.
The role of race/ethnicity, psychiatric history, and substance use in the risk of dementia subtypes: Findings from the NACC
Authors: Aranda Maria P , Liang Jiaming , Wang Xinhui , Chui Helena C , Schneider Lon S
Published: December 2021

Background

Dementia is characterized by significant declines in cognitive and physical functioning and includes multiple subtypes that differ in etiology. There is limited evidence of the influence of psychiatric and substance use history on the risk of dementia subtypes among underrepresented racial/ethnic minorities. The study explored the role of psychiatric and substance use history on the risk of etiology‐specific dementias: Alzheimer’s disease (AD) and vascular dementia (VaD), in the context of a racially and ethnically diverse sample based on national data in the US.

Method

We conducted secondary data analyses based on the National Alzheimer’s Coordinating Center Uniform Data Set (N = 17,592). Participants completed at least two visits and were dementia‐free at baseline, and were assessed for history of five psychiatric and substance use disorders (depression, traumatic brain injury, other psychiatric disorders, alcohol use, and other substance use). Cox proportional hazard models were estimated to examine the influence of psychiatric and substance use history on the risk of two dementia subtypes, and the interactions between psychiatric and substance use history and race/ethnicity with adjustment for demographic and health‐related factors.

Result

In addition to other substance use, having any one type of psychiatric and substance use history increased the risk of developing AD by 22‐51% and VaD by 22‐53%. The risk of other psychiatric disorders on AD and VaD risk varied by race/ethnicity. For Non‐Hispanic White, history of other psychiatric disorders increased AD risk by 27% and VaD risk by 116%. For African Americans, AD risk increased by 28% and VaD risk increased by 108% when other psychiatric disorder history was present.

Conclusion

The findings indicate that having psychiatric and substance use history increases the risk of developing AD and VaD in later life. Preventing the onset and recurrence of such disorders may prevent or delay the onset AD and VaD dementia subtypes. Prevention efforts should pay particular attention to Non‐Hispanic White and African American older adults who have history of other psychiatric disorders.
Greater adolescent cognitive ability is linked to lower risk of cognitive impairment in later life
Authors: Gruenewald Tara L , Arpawong Thalida Em , Zavala Catalina , Grossman Molli , Walters Ellen E , Peters Kelly , Lapham Susan , Manly Jennifer J , Gatz Margaret , Prescott Carol Arlene
Published: December 2021

Background

There have been few investigations of the role that adolescent cognitive ability might play in predicting who will later develop cognitive impairment. This is due, in part, to a lack of cohorts with early‐life cognitive assessment who have been followed to later adulthood. We capitalized on the 1960 Project Talent high school cohort to assess whether higher adolescent cognitive ability predicted lower risk of impaired cognitive function in older adulthood. A subsample of twin and non‐twin siblings allowed for assessment of whether these associations are due to shared family and genetic factors.

Method

Data come from the 1960 Project Talent (PT) baseline data collection (n>360,000) and two follow‐ups: the Project Talent Twin & Sibling (PTTS; n=2,491) Study and the Project Talent Aging Study (PTAS; n=6,421). The 1960 data collection assessed performance in multiple cognitive abilities (see Table 1). In 2018, participants/proxies reporting 2 or more symptoms of cognitive impairment on the AD8 Dementia Screener were classified as having a positive screen. Binary logistic generalized estimating equations assessed odds of a positive AD8 screen as a function of 1960 cognitive abilities. Models included age, race, sex, adolescent family SES, and adult educational attainment covariates. Co‐sibling control models examined whether associations remained when accounting for shared family and genetic characteristics.

Results

Covariate‐adjusted models indicated that each 1 SD higher adolescent cognitive ability predicted lower odds of a positive AD8 screen in later life for most ability domains (e.g., general cognitive ability OR = 0.86 (95% CI = 0.76, 0.98), see Table 1); associations were attenuated somewhat with inclusion of adult educational attainment in models. Preliminary co‐sibling control analyses indicated the persistence and strengthening of this association (OR = 0.57 (95% CI = 0.36, 0.91)).

Conclusion

Findings indicate that greater performance in multiple cognitive domains in adolescence predicts lower risk of cognitive impairment over 5 decades later. A co‐sibling control analysis indicated that the link between adolescent general cognitive ability and later‐life cognitive impairment is not simply due to shared family background and genetic factors. Ongoing analyses are assessing whether this is true for other cognitive domains and other indicators of cognitive function.
Methodological challenges across WW‐FINGERS Studies: Impact of COVID‐19 pandemic on statistical design and analysis plans for multidomain RCTs
Authors: Espeland Mark A , Roehr Susanne , Arai Hidenori , Mangialasche Francesca , Peltonen Markku , Raman Rema , Riedel‐Heller Steffi G , Snyder Heather M , Carrillo Maria C , Ngandu Tiia , Kivipelto Miia
Published: December 2021

Background

The coronavirus disease‐19 (COVID‐19) pandemic presents challenges to the conduct of randomized clinical trials of lifestyle interventions.

Method

World‐Wide FINGERS is an international network of clinical trials to assess the impact of multidomain lifestyle intervention on cognitive decline in at‐risk adults. Individual trials are tailoring successful approaches from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) to local cultures and environments. The network convened forums for researchers to discuss statistical design and analysis issues they faced during the pandemic. We will provide an updated report on experiences of trials that, at various stages of conduct, altered designs and analysis plans to navigate these issues. We provide recommendations for future trials to consider as they develop and launch behavioral intervention trials.

Result

The pandemic led researchers to change recruitment plans, interrupt timelines for assessments and intervention delivery, and move to remote intervention and assessments protocols. The necessity of these changes add emphasis to the importance, in study design and analysis, of intention to treat approaches, flexibility, within site stratification, interim power projections, and sensitivity analyses.

Conclusion

Robust approaches to study design and analysis are critical to negotiate issues related to the intervention. The World Wide Network of similarly oriented clinical trials will allow us to evaluate the effectiveness of responses to the pandemic across cultures, local environments, and phases of the pandemic.
Metabolism in frontotemporal dementia
Authors: Ahmed Rebekah M
Published: December 2021

Background

Metabolic changes incorporating changes in weight, insulin resistance and cholesterol levels have been identified across a number of neurodegenerative conditions. It remains unknown whether these changes represent the result of the process of neurodegeneration affecting critical brain regions involved in metabolic regulation, or are causative, driving the process. Changes in eating behaviour affecting metabolism have been incorporated into the diagnostic criteria for frontotemporal dementia (FTD), and have been shown to potentially effect disease progression, with the potential to aid in clinical phenotyping and early diagnoses.

Methods

A number of studies will be reviewed examining changes in eating behaviour in FTD using ecological valid assessments including a test meal approach. The effect that these eating changes have on metabolism will be examined, including changes in cholesterol, and insulin levels and metabolic rate. The role of key brain regions including the hypothalamus will be explored through a number of studies incorporating brain imaging, neuropeptide examination and pathological analyses.

Results

Patients with FTD exhibit a strong fat and sucrose preference, that is not present in normal or Alzheimer’s disease controls. These changes result in increased cholesterol levels and a state of insulin resistance which has been associated with changes in disease progression. Patients with FTD have been found to be hypermetabolic, with increased cholesterol levels, from changes in eating behaviour, likely resulting in improved energy stores in a hypermetabolic state and potentially slowing disease progression. Changes in eating behaviour and metabolism have been linked to changes in key neural networks involving fronto‐insular‐ striatal networks, with connections to the hypothalamus. Changes in key hypothalamic peptides including agouti‐related peptide and leptin have also been implicated in mediating metabolic changes and changes in disease progression.

Conclusions

Given the spectrum of metabolic and eating changes observed in FTD, with emerging evidence that these changes may effect disease progression and prognoses, an understanding of metabolism in FTD may provide a model to better understand the pathophysiology of metabolic change and its complex interaction with the process of neurodegeneration.
Clinical characteristics and treatments in patients with chronic kidney disease and dementia
Authors: Xu Hong , Garcia‐Ptacek Sara , Eriksdotter Maria , Carrero Juan Jesus
Published: December 2021

Background

There is limited information on clinical features and treatments of patients with chronic kidney disease (CKD)–associated dementia. In this study, we assessed the difference in dementia diagnoses, cognitive function, and dementia treatment among patients with and without CKD.

Method

We included 20,032 patients with newly diagnosed dementia from the Swedish Dementia Registry (SveDem) within the region of Stockholm during 2006‐2018. Patient baseline kidney function was extracted from the Stockholm CREAtinine Measurements (SCREAM) project, and categorized by estimated glomerular filtration rate (eGFR) as ≥60, 30‐59, 15‐29, and <15 ml/min/1.73m2 or dialysis. Dialysis patients were identified via linkage with Swedish Renal Registry. The difference in dementia diagnosis, cognitive function, dementia treatment among patients with different eGFR strata were examined. Confounders included demographics, living conditions, comorbidities, and therapies.

Result

Among the dementia patients 70% had GFR≥60ml/min, 27% GFR 30‐59ml/min, 2% GFR 15‐29ml/min and 1% <15 % ml/min or with dialysis. The proportion of vascular dementia increased across lower eGFR categories, while Alzheimer’s and mixed dementia, dementia with Lewy Bodies and Parkinson's disease dementia decreased. Patient diagnosis in nursing home, the use of renin‐angiotensin‐system‐inhibitors, calcium‐channel‐blockers, and statins increased while antipsychotics and antidepressants decreased. Compared with eGFR ≥60 ml/min, lower eGFR strata were associated with worse cognitive function (MMSE unit, adjusted β coefficient, ‐0.69, 95% confidence interval [‐1.22,‐0.17] for eGFR 15‐29ml/min and ‐1.50, (‐2.66,‐0.34) for eGFR<15ml/min or dialysis). After adjustment for patient demographics, living conditions, comorbidities, MMSE and therapies, lower eGFR strata were significantly associated with less prescription of acetylcholinesterase inhibitors (aChEIs) and memantines [Odds ratio 0.91(0.84‐0.99) in eGFR 30‐59ml/min and 0.20 (0.09‐0.46), in eGFR<15ml/min or dialysis for aChEIs; 0.91(0.83‐0.99) in eGFR 30‐59ml/min, 0.37 (0.25‐0.55) in eGFR 15‐29ml/min and 0.14(0.03‐0.58), in eGFR<15ml/min or dialysis for memantine use].

Conclusion

Patients with advanced chronic kidney disease had worse cognitive function and less prescribed anti‐dementia drugs. Since we have previously shown that aChEI treatment is associated with lower mortality, the relationship between anti‐dementia medication, renal function and cognition must be further investigated.
Disease progression models of familial frontotemporal lobar degeneration and the temporal ordering of biomarker changes in an international cohort
Authors: Staffaroni Adam M. , Quintana Melanie , Wendelberger Barbara , Russell Lucy L. , Petrucelli Leonard , Gendron Tania F. , Goh Sheng‐Yang Matthew , Cobigo Yann , Wolf Amy , Heuer Hilary W. , Cash David M. , Ong Elise , Forsberg Leah K. , Brushaber Danielle , Bahl Riley , Heller Carolin , Bouzigues Arabella , Swift Imogen J. , Peakman Georgia , Bocchetta Martina , Todd Emily G. , Convery Rhian S. , Boeve Bradley F. , Rosen Howard J. , Rohrer Jonathan D. , Boxer Adam L. ,   ALLFTD and GENFI
Published: December 2021

Background

Clinical trials are underway to treat familial frontotemporal lobar degeneration (f‐FTLD). This is a rare disease, and a limited number of mutation carriers have been identified; thus, efficient trial design is critical. Multimodal, latent disease progression models (DPM) can estimate time to symptom onset and define the temporal ordering of biomarker changes. DPMs can also be leveraged to select endpoints and potentially supplement analyses by integrating historical data. Recent draft FDA guidance for gene therapy trials in neurological disease supports these novel approaches to clinical trials.

Method

Participants included 1,049 members of families affected by f‐FTLD, due to mutations in GRN, MAPT, or C9orf72 genes, who were enrolled in ALLFTD or GENFI. A Bayesian repeated measures model incorporated multimodal data to estimate disease progression, conditional on latent disease age (proximity to symptom onset), in 677 mutations carriers (GRN (n=233), MAPT (n=151) and C9orf72 (n=293)). Family members without pathogenic mutations were used as the reference group. Mean follow‐up was 1.1 (SD=1.1) years. Jointly modeled longitudinal variables included neuropsychological scores, CDR®+NACC‐FTLD Box Score, MRI volumes of brain regions affected by f‐FTLD, and plasma levels of neurofilament light chain (NfL).

Result

Disease progression curves were similar across ALLFTD and GENFI cohorts. Plasma NfL elevations occurred earliest, up to 10 years before symptom onset, and NfL was the most powerful endpoint in the asymptomatic stage. MRI abnormalities occurred next, closer to symptom onset. The earliest MRI changes relative to symptom onset were observed in C9orf72+. GRN mutation carriers showed the most rapid acceleration in all biomarkers, and this acceleration occurred in close proximity to symptom onset. Neuropsychological measures and CDR®+NACC‐FTLD Box Score were among the most promising endpoints in the symptomatic stage. Trial simulations indicated that using latent disease age as an enrollment criterion would allow some asymptomatic mutation carriers to be enrolled without sacrificing power.

Conclusion

Similarity in disease progression across ALLFTD and GENFI participants suggests these models will apply to international trials. Model‐derived estimates of disease progression curves indicate that endpoint selection should be specific to disease stage and mutation, and DPMs would facilitate greater participant enrollment.
The joint effects of audio and linguistic markers for early identification of mild cognitive impairment
Authors: Tang Fengyi , Chen Jun , Dodge Hiroko H , Zhou Jiayu ,   I‐CONECT
Published: December 2021

Background

In recent years, speech‐related behavioral markers such as spoken language and lexical preferences have been studied in the early detection of mild cognitive impairment (MCI). While the combination of linguistic and acoustic signals has been shown to be effective in detecting MCI, they have generally been restricted to structured conversations in which the interviewee responds to fixed prompts. In this study, we propose a stratification scheme that proves to be effective in extracting quality linguistic and acoustic MCI markers in semi‐structured more natural conversational settings.

Method

We obtained transcripts and audio recordings from an ongoing single blind randomized controlled clinical trial NCT02871921. Briefly this clinical trial aims to improve psychological well‐being and cognitive functions of the non‐demented (normal or MCI) older adults aged 75 and older by enhancing their social interactions. The experimental group receives 30 minutes of semi‐structured conversations (video chats) with interviewers four times per week, for up to one year. Recruitment started in July 2018 and we used the data from the first 39 participants enrolled in the experimental group with audio and transcribed data as of March 2020 in the current analysis. Our stratification scheme eliminates drastic train‐test distribution mismatch, allowing for apples‐to‐apples comparison across participant conversations, despite drastic variations in word choices, sentence structure and length of conversations – obstacles that typically present challenges to the semi‐structured conversational setting for automatic acoustic marker extraction.

Results

Figure 1 gives an overview of our MCI prediction pipeline. The combination of linguistic and audio features achieve a mean AUC of 82.7, significantly (p<0.01) out‐performing linguistic‐only (AUC = 74.9) or acoustic‐only (AUC = 65.0) detections on hold‐out data. Our subtopic stratification method identifies several conserved clusters (Figure 2) in interview structure, allowing more balanced train‐test split in terms of linguistic properties, despite the semi‐structured nature of conversations.

Conclusion

A combination of linguistic and audio features improves the ability to detect MCI beyond that achieved by each feature alone in semi‐structured conversation. Our method provides a potentially valuable approach for using speech for early detection of MCI and clinical trials enrichment.
Characterizing blood‐based, microglial derived exosomes (MDEs) as biomarkers for Alzheimer’s disease
Authors: Winston Charisse N. , Sarsoza Floyd , Spencer Brian , Rissman Robert A.
Published: December 2021

Background

Recent studies suggest neuronal and astrocyte‐derived exosomes may serve as the source of biomarkers for many neurodegenerative diseases, include AD. However very few studies have characterized the biomarker potential of microglial derived exosomes.

Method

Plasma exosomes were extracted and precipitated from AD patients and age matched controls. Extracted exosomes were enriched against a microglial source (TMEM119) using magnetic immunocapture and fluorescence‐activated cell sorting (FACS) sorting. MDEs were characterized by size (Nanosight) and shape (TEM). Exosome marker profiling was done by western blot. MDE cargo proteins will be quantified to identify biomarkers for stages of AD using ELISA.

Result

Blood‐based MDEs demonstrate similar size distributions and shape to previously reported exosome preparations. Western Blot demonstrated that MDEs were positive for exosome marker Flotilin‐1; microglial markers CD68 and IBA1 and negative for astrocyte marker, GLAST. Further characterization of MDE protein cargo levels, which include AD‐related (Aβ and p‐tau) and inflammatory markers, will be analyzed and presented.

Conclusion

MDEs can be successfully isolated from human blood with the hope that they also demonstrate biomarker potential for AD, akin to other CNS‐derived exosomes.
The impact of built and social environmental characteristics on incidence and estimated risk of dementia
Authors: Bagheri Nasser , Mavoa Suzanne , Tabatabaei‐Jafari Hossein , Knibbs Luke D , Coffee Neil T , Salvador‐Carulla Luis , Anstey Kaarin J
Published: December 2021

Background

Dementia is a public health priority1 and the current study designed to investigate associations between built and social environmental characteristics and dementia incidence, and the estimated future risk of dementia. Further we investigated spatial variations in dementia risk and dementia incidence to identify unmet areas for policy intervention.

Method

We used 25,511 patients (aged 65 years and older) records in Adelaide between 2011‐2015. In addition to dementia incidence, we calculated a dementia risk score based on risk and protective factors for patients not diagnosed with dementia. The following built and social environment exposures were estimated for each statistical area level 1 (SA1)2: social fragmentation, nitrogen dioxide (NO2), public open spaces, walkability, socio‐economic status and the length of main roads. We performed multilevel regression analyses to allow for the hierarchical nature of the data and applied spatial cluster analysis to identify areas with high and low risk of dementia.

Result

We found that a one standard deviation (SD) increase in NO2 and walkability score was associated with 10% higher odds of any versus no dementia (95% confidence interval (CI): 1%, 21% for NO2 and 0%, 22% for walkability score). For estimated future risk of dementia, a 1‐SD increase in social fragmentation (mobility component) and NO2 was associated with a 1% increase in dementia risk (95% CI: 0, 1%). 1‐SD increases in public open space and socioeconomic status were associated with 3% (95% CI: 0.95, 0.98) and 1% decreases (95% CI: 0.98, 0.99) in dementia risk, respectively. There was spatial heterogeneity in the pattern of dementia incidence and dementia risk.

Conclusion

Associations of neighbourhood NO2 level, walkability, public open space and social fragmentation with dementia incidence and estimated future risk of dementia were statistically significant, indicating the potential to reduce the risk through changes in built and social environments. Mapping the estimated future risk of dementia and diagnosed cases of dementia offers a novel approach to identifying areas of unmet need. 1. Towards a dementia plan: a WHO guide. Geneva: WHO; 2018. 2. Australian Statistical Geography Standard (ASGS): Volume 1 ‐ Main Structure and Greater Capital City Statistical Areas, 2016.
The improvement effects of Orengedokuto for aggression and violence to caregiver’s care from patients with dementia
Authors: Urabe Shinji , Tsuchida Hideto , Tamura Junichi , Nabika Toumei , Shirakikawa Shinsuke , Yoshikawa Yoshimi , Moritoki Yukihiro , Matsuo Koji , Tsunemi Teppei , Wada Takatosi , Shiomoto Takayuki , Urabe Mie
Published: December 2021

Background

Behavioral and psychological symptoms of dementia (BPSD) increase the distress of patients with dementia and the burden for care givers and they are the symptoms that need to be solved immediately. Antipsychotics are not recommended for the treatment of aggression and violence in BPSD, because they make the risk of death of the elderly according to Food and Drug Administration (FDA, 2005). So, as a medicine with less side effects which give the expected effect, herbal medicine is used often for BPSD in Japan. We have focused on Orengedokuto within Japanese herbal medicine, and reported that it improve the aggression (Urabe et al., AAIC2019) and behavioral deviation and the rejection of care by patients with dementia ((Urabe et al., AAIC2020) in AD. The purpose of this research is to clarify the effect of Orengedokuto to aggression and violence of patients with dementia.

Method

The subjects were 11 patients with dementia admitted to a psychiatric hospital in Japan. The group of the patients with dementia who were administered with Orengedokuto (ODG;8 patients, average age ; 83 years old) and a control group of the patients with dementia who did not take Orengedokuto (NODG; 3 patients, average age; 80.3 years old). We evaluated the patients with Behavioral Pathology in Alzheimer’s disease (Behave‐AD), Mini Mental State Examination, the improvement effects of aggression and violence were compared the changes before and after administration between ODG and NODG. There is no conflict of interest in this study.

Result

The average score of aggression and violence, was 7.25 point (before administration: before) to 1.5 point (at the time of leave from hospital: after) in ODG (p<0.05), and 7.6 point (before) to 4.6 point (after) in NODG.

Conclusion

In ODG, aggression and violence behavior was improved. It was clarify that Orengedokuto has the improve effect of aggression. And it was suggested that Orengedokuto has the improve effect of violence behavior related aggression, too.
Subjective cognitive decline and self‐reported sleep at a memory clinic: The SCIENCe project
Authors: Exalto Lieza G , Hendriksen Heleen MA , Barkhof Frederik , van den Bosch Karlijn A , Ebenau Jarith L , van Leeuwenstijn Mardou , Prins Niels D , Teunissen Charlotte E , Visser Leonie NC , van der Werf Ysbrand D , Scheltens Philip , van der Flier Wiesje M
Published: December 2021

Background

sleep problems have been associated with Alzheimer’s disease (AD) pathology and they have been suggested to occur early in the disease process. Sleep problems have also been associated with subjective cognitive decline (SCD), although in many subjects with SCD, no AD biomarker evidence is found for the experienced cognitive decline. Our aim was to investigate whether frequency and type of sleep problems in memory clinic patients with SCD are associated with cognition, mental health, MRI measures, and AD CSF biomarkers.

Method

308 subjects (65±8yrs, 44% female, MMSE 29±1) from the Subjective Cognitive Impairment Cohort (SCIENCe) project with available information on sleep were included. Sleep was evaluated by the Berlin Questionnaire (3 categories; ≥2 high risk sleep apnea) and Pittsburgh Sleep Quality Index (range 0‐21; ≥5 poor sleep quality). All underwent a standardized memory clinic work‐up. Subjects were classified as having sleep problems when ≥1 sleep questionnaire was above the cut‐off. Sociodemographics, cognitive performance (attention, memory, language, and executive functioning), depressive symptoms, anxiety, self‐reported cognitive decline (Cognitive Change Index; CCI), medial temporal lobe atrophy, global cortical atrophy, white matter hyperintensities, and CSF levels of Aβ42, t‐tau, p‐tau were compared between subjects with and without sleep problems.

Result

198/308 (64%) subjects reported sleep problems, based on 107 (35%) sleep apnea and 162 (53%) poor sleep quality. Subjects with sleep problems tended to be younger (63.8±8.1 vs 65.7±8.5), more often female (47% vs 39%) and more often APOE ε4 carrier (40% vs 28%), but these differences did not reach statistical significance (all p>.05, Table 1). They reported more depressive symptoms (CES‐D median(IQR): 10(5‐16) vs 4(2‐7)), anxiety (HADS‐A: 5(2‐10) vs 2(0.25‐4)) and cognitive decline (CCI: 43(31‐56) vs 35(25‐47)), all p≤.001. Sociodemographics, cognitive performance, MRI measures and AD CSF biomarker levels did not differ between groups.

Conclusion

sleep problems are common in subjects with SCD and are associated with higher levels of anxiety, depressive symptoms and self‐reported cognitive decline, but not AD biomarkers. Our results suggest that poor sleep quality and hygiene are a potentially reversible cause of the subjective experience of cognitive decline and potential leads for treatment in many subjects with SCD.
Characterization of the NIA‐AA Research Framework stage 2 in the longitudinal multicenter DELCODE study
Authors: Sannemann Lena , Meiberth Dix U. , Schild Ann‐Katrin , Bürger Katharina , Heneka Michael T. , Laske Christoph , Perneczky Robert , Peters Oliver , Priller Josef , Schneider Anja , Spottke Annika , Teipel Stefan J. , Wagner Michael , Wiltfang Jens , Wolfsgruber Steffen , Düzel Emrah , Jessen Frank ,   the DELCODE study group
Published: December 2021

Background

The latest NIA‐AA Research Framework for Alzheimer’s disease (AD) includes a numerical staging system for individuals in the Alzheimer’s continuum. The authors introduce “stage 2” as a transitional stage, characterized by the earliest detectable cognitive or neurobehavioral changes. We aimed to characterize stage 2 in a large German multicentre cohort study.

Method

Our analysis included baseline data of N = 349 cognitively healthy participants with available CSF biomarker information from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study. A subsample of n = 110 participants presented with abnormal Aß42/40 biomarkers and was therefore classified as part of the Alzheimer’s continuum. Stage 2 characteristics at baseline were defined by subjective decline with concern in any domain on the SCD interview that persisted for at least 6 months. In addition, subtle impairment of objective cognitive performance (<0,5SD) was derived from factor scores of the DELCODE neuropsychological test battery. Subtle neurobehavioral changes were defined by the presence of at least one neuropsychiatric symptom (NPS) on the Neuropsychiatric Inventory Questionnaire (NPI‐Q).

Result

The majority of participants in the Alzheimer’s continuum presented with only SCD (22.7%) or both SCD and NPS (20.9%), whereas 12.7% presented with only NPS and 5.5% with only subtle objective cognitive decline. While 10.9% showed all three stage 2 characteristics, 14.5% showed none. The distribution of stage 2 characteristics differed between participants in the Alzheimer’s continuum and those with normal Aß42/40 (X2
(7)=21.21, p<.01). In addition, the number of fulfilled stage 2 criteria was higher in participants with abnormal Aß42/40 (M=1.41, SD=0.87) compared to those with normal amyloid biomarkers (M=1.10, SD=0.84, t(347)=1.45, p=.001).

Conclusion

Our findings provide a systematic overview on stage 2 characteristics in a large cohort of cognitively healthy participants with abnormal AD biomarkers and indicate that both the number of fulfilled stage 2 criteria and their distribution differs from participants outside the Alzheimer’s continuum.
Impairment of recognition of facial expressions in different types of dementia
Authors: Güntekin Bahar , Yıldırım Ebru , Kıyı İlayda , Akturk Tuba , Calısoglu Pervin , Uzunlar Hakan , Yirikogullari Harun , Helvacı‐Yılmaz Nesrin , Bayraktaroglu Zubeyir , Hanoğlu Lutfu , Sequeira Henrique , Yener Gorsev
Published: December 2021

Background

Impairment of facial expression recognition in dementia is one of the cognitive deficits that could affect the social life of dementia patients. The severity of the facial expression recognition in different types of dementia has not been fully addressed. Previous studies showed that EEG event‐related oscillation (ERO) studies could reveal the brain dynamics during successful facial expression recognition. Furthermore, the impairment of facial recognition in Alzheimer's disease patients were represented with abnormal EROs (Güntekin et al., 2019). The present study aims to compare the impaired facial expression recognition between different types of dementia by analysis of event‐related delta responses. The role of delta responses in facial expression and emotional paradigms was reported previously by several researchers (Güntekin and Başar, 2014).

Method

25 Healthy elderly controls (HC), 25 Mild Cognitive Impairment patients (MCI), 25 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease with Mild Cognitive Impairment (PDMCI) and 16 patients with Parkinson's disease Dementia (PDD) were included in the study. The electroencephalographic activity was recorded during the perception of the facial expression recognition task (Angry, Happy, Neutral). Delta power and phase‐locking were computed for each facial recognition stimuli and compared among the groups (ANOVA, p<0.05).

Result

Both delta power and delta phase locking were lower in dementia groups than healthy controls being worst in PDD. Figure 1 shows the grand average of delta power in all groups for the right occipital location. PDD (p<0.0001) and AD (p<0.05) had lower delta power than the healthy controls, the reduction of delta responses in PDD and AD were especially found over occipital locations. MCI and PDMCI subjects were found less impaired facial expression recognition compared to AD and PDMCI.

Conclusion

The present study showed that dementia patients had severe facial recognition deficits that increased cognitive impairment. Event‐related delta responses successfully showed the impaired recognition of facial expression in different types of dementia groups. Among all dementia subjects, PDD patients had the most reduced delta responses that could be an electrophysiological biomarker of impaired facial expression recognition. Acknowledgments: This work (grant number 218S314) was supported by TUBITAK. References: 1) https://doi.org/10.1111/psyp.13434.2) https://doi.org/10.1016/j.neuropsychologia.2014.03.014
A stepwise approach towards diagnostic workup in dementia using online cognitive tools
Authors: Meester Hanneke FM Rhodius‐ , Tolonen Antti , Van Gils Aniek M , Koikkalainen Juha , Barkhof Frederik , Herukka Sanna‐Kaisa , Hänninen Tuomo , Ngandu Tiia , Kivipelto Miia , Hasselbalch Steen Gregers , Mecocci Patrizia , Remes Anne , Soininen Hilkka , Scheltens Philip , van der Flier Wiesje M , Lötjönen Jyrki
Published: December 2021

Background

Dementia affects more and more people worldwide. Unfortunately, only half of dementia cases are well recognized. This indicates a need for both efficient and tailored tools for diagnosis. To improve the number of correctly diagnosed patients while retaining cost‐effectiveness, we study a stepwise data‐driven approach for the diagnostic workup. By using the online cognitive test tool cCOG [1] as prescreener, we aim to select the right diagnostic workup for each patient.

Methods

We included 710 subjects from three memory clinic cohorts (PredictND, VPH‐DARE and Amsterdam dementia cohort) with different types of dementia and subjective cognitive decline (SCD). All patients performed a neuropsychological (NP) test battery (consisting of MMSE, RAVLT, TMT‐A and B and Animal Fluency) and had MRI of the brain. A subset of 214 subjects additionally performed cCOG. To verify results we imputed missing cCOG based on corresponding NP tests [1]. From MRI, multiple imaging biomarkers were defined [2]. We tested a stepwise diagnostic approach, starting with screening using cCOG, then if needed testing with NP test battery and MRI, using the Disease State Index (DSI) classifier [2]. At each step patients were selected for the next step based on DSI model’s confidence (Figure 1).

Results

The stepwise approach was as accurate as performing all tests in every patient (Table 1), but it reduced the number of tests done especially in SCD patients considerably, with NP in only 57% and MRI in 38% (Table 2). This was also reflected in reduced cost per patient in typical memory clinic population (from estimated 510 € to 238‐243 €). For dementia patients the reduction in number of tests and costs was smaller.

Conclusion

This study suggest that using a stepwise approach, applying online cognitive tests as prescreening at home, can reduce the number of patient visits to clinic and costs. The results were as accurate as with the standard traditional work‐up. Online cognitive testing is therefore a promising tool to funnel the patient flow to memory clinics, also in times of social distancing. References: [1] Rhodius‐Meester, H.F.M. et al. Alzheimers Dement 2020 Aug25;12(1) [2] Bruun, M. et al. Alzheimers Dement 2018 Aug17;10.
Tau368 in cerebrospinal fluid is associated with severity of tau pathology load in the Alzheimer’s continuum
Authors: Simrén Joel , Benedet Andréa Lessa , Ashton Nicholas J. , Pascoal Tharick A. , Zetterberg Henrik , Rosa‐Neto Pedro , Blennow Kaj
Published: December 2021

Background

Recent developments in the biomarker field allow Alzheimer’s disease (AD) pathophysiology to be reflected at the preclinical stage. We recently presented an assay targeting tau fragments ending at residue 368, which exhibited a stage‐wise decrease in a ratio with total‐tau. The tau368/T‐tau ratio also correlated with tau positron emission tomography (PET) uptake, and was present in tau tangles. In this study, we aimed to validate these findings in a larger cohort including a larger subset spanning the AD continuum.

Method

We investigated 129 participants cross‐sectionally from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort (22 young, 60 cognitively unimpaired (CU) elderly (14 Aβ+), 26 mild cognitive impairment (MCI; 10 Aβ+), 14 AD dementia and 7 frontotemporal dementia (FTD)). For all individuals, [18F]AZD4694 and [18F]MK‐6240 PET were used to index Aβ and tau load (Braak stages) respectively. T‐tau was quantified using ELISA (INNOTEST®) and Tau368 was quantified by an in house Single molecule array (Simoa) assay (Quanterix, Billerica, MA). Spearman rank tests assessed correlation between continuous variables. Linear models tested the effect of tau368/t‐tau ratio on PET summary measures and at the voxel level, always adjusting for age and sex.

Result

Compared to young controls, we observed a stage‐wise decrease of tau368/t‐tau, with the lowest ratio found in AD dementia (P<0.01), followed by CU‐ (P<0.001), CU+ (P<0.01) and MCI‐ (P<0.001). MCI+ had a lower ratio than CU‐ (P<0.01). Furthermore, there was a strong negative correlation between tau368/t‐tau ratio and PET Braak stages in the whole population (I‐II; ρ=‐0.46, P<0.001, III‐IV; ρ=‐0.44, P<0.001, V‐VI; ρ=‐0.37, P<0.001), in MCI+ (I‐II; ρ=‐0.79, P<0.01, III‐IV; ρ=‐0.84, P<0.01, V‐VI; ρ=‐0.83, P<0.01) and in AD dementia (V‐VI; ρ=‐0.57, P<0.05). Voxel‐wise analysis demonstrated strong correlation between tau368/t‐tau and tau PET ligand uptake in the medial and lateral temporal lobes in cognitively impaired individuals, while no significant association was found in CU.

Conclusion

We provide further evidence of a stage‐wise decrease in CSF tau368/t‐tau, which tracks cortical tau accumulation only in clinically manifest AD dementia and amyloid positive MCI. These results further support that CSF tau368/t‐tau captures severity of tau pathology within the AD continuum.
Can community‐based cognitive screening identify individuals with MCI associated changes in complex instrumental activities of daily living?
Authors: Marks Timothy S , Giles Gordon Muir , Edwards Dorothy Farrar
Published: December 2021

Background

Unrecognized deficits in complex instrumental activities of daily living, termed “preclinical disability”, have been identified in individuals experiencing mild cognitive impairment (MCI: Fieo & Stern, 2018; Peterson et al., 2017). Screening for difficulties in the performance of cognitively demanding complex IADLs may facilitate earlier identification of people on the threshold of MCI and can facilitate earlier intervention (Rodakowski et al., 2014). We examined the ability of three cognitive screening tests to identify individuals reporting IADL problems on the ADCS‐ADL‐MCI scale.

Methods

A sample of 87 adults living independently in the community were assessed with the Menu Task, Mini‐Cog, Montreal Cognitive Assessment (MoCA), the ADCS‐ADL, and the 18 and 24 item versions of the ADCS‐MCI‐ADL scale. Established cut‐off scores for each cognitive screen identified impaired and unimpaired groups. Mann‐Whitney U tests compared differences between unimpaired and impaired groups for each cognitive screen on the 18 and 24 item ADCS‐MCI‐ADL composite scores. Between group differences were also examined for each of the ADCS‐MCI‐ADL‐24 individual items.

Results

Sample demographics are presented in Table 1. Individuals impaired on the Menu Task had significantly lower composite scores on both the ADCS‐MCI‐ADL‐18 and the ADCS‐MCI‐ADL‐24 (p < .01), although no significant composite score differences were found for the Mini‐Cog (p = .061, p = .155) or the MoCA (p = .053, p = .099). Individual ADCS MCI items were also analyzed to explore the types of IADL impairments identified by each of the three cognitive screens scales. Different patterns of IADL impairment emerged for each of the cognitive screening measures. Individuals impaired on the Mini‐Cog had significantly lower ADCS‐ADL composite scores (p < .05).

Conclusion

Individuals living in the community who score as impaired on the Menu Task demonstrated significantly lower ADCS‐MCI‐ADL‐18 and ADCS‐MCI‐ADL‐24 composite scores, but no significant difference on ADCS‐ADL. Impairment on each of the cognitive screening measures was associated with lower scores on individual ADCS‐ADL‐MCI complex IADL items. Cognitive screening measures that detect early and subtle changes in function may lead to earlier diagnosis and interventions for cognitively complex IADL deficits.
Overlooked threats to person‐centered dementia care: An imperative to explore the family terrain
Authors: Podgorski Carol Ann
Published: December 2021

Background

Adoption of person‐centered care practices for older adults has increased considerably across the United States in recent years. This momentum is due largely to the dissemination of evidence‐based models including those delineated in both the Alzheimer’s Association® Dementia Care Practice Recommendations (2018) and the Age‐Friendly Health System initiative (2018). Both frameworks call for health care providers to work collaboratively with patients and their families to deliver care in accordance with what matters most to the patient. The role of family, particularly in person‐centered dementia care, generally involves informing, interpreting, and advocating for the patient. In healthy, well‐functioning families with strong attachment bonds and clear, open communication, the family is likely to know the patient’s wishes and to act in their best interest. In fractured, wounded families, however, this is less often true. Limited knowledge and understanding of the patient’s family dynamics preclude consideration of the complex, interdependent nature of family relationships and how those relationships influence not only the patient information that family members share, but also how they interpret information that gets exchanged with health care providers, and how the dynamics shape the goals of care for which families advocate. Family dynamics also influence whether and how care plans are implemented, which inevitably affects patient quality of life along with health care outcomes and costs. Evidence suggests that patients with dysfunctional families often require more careful monitoring regarding care compliance. Family history and relational dynamics pose threats to effective delivery of person‐centered care in a number of important ways including, for example: whether a family member will commit to step into the caregiver role and to what extent; whether, how, and when advance care planning takes place; and whether interdependent family relationships create power dynamics that lead to misrepresentation of the patient’s wishes, elder mistreatment, or family violence. This presentation will provide evidence to support a call for person‐centered care approaches to incorporate screening and assessment of patient and family relationship history as a means to better ensure the delivery of person‐centered dementia care that promotes safety as well as compliance with legal and ethical standards.
Social cognition provides early distinction between phenocopy syndrome of behavioural variant frontotemporal dementia and behavioural variant frontotemporal dementia
Authors: van Engelen Marie‐Paule E. , Louwers Paulette , Gossink Flora T , Krudop Welmoed A. , de Boer Sterre C.M. , Dols Annemiek , Schouws Sigfried , Scheltens Philip , Vijverberg Everard G.B. , Pijnenburg Yolande A.L.
Published: December 2021

Background

Patients displaying clinical features of bvFTD but lacking abnormalities on neuroimaging in the absence of clinical progression over time are considered to represent the phenocopy syndrome of bvFTD (phFTD). Clinical overlap between bvFTD and phFTD hampers their diagnostic distinction whereas it is essential to provide adequate treatment and prognosis. We aimed to assess whether there are differences in patient characteristics and caregiver‐reported symptoms between phFTD and bvFTD that can provide tools for early distinction.

Method

We compared phFTD with probable/definite bvFTD with respect to patient characteristics and caregiver‐reported symptoms, that comprised the domains behaviour, global cognitive functioning, social cognition and ADL. Total test scores were compared between groups followed by multiple logistic regression analysis. ROC curves were plotted to assess diagnostic value.

Result

A total of 53 patients were included (n = 28 phFTD, n= 25 bvFTD). Compared to bvFTD, phFTD patients performed better in terms of social cognition yet had more behavioural symptoms and worse ADL performance reported by the caregiver. When combining social cognition, behavioural symptoms and ADL performance we found a sensitivity and specificity of 85.71% and 80.0% for a diagnosis of phFTD.

Conclusion

Social cognition was spared in phFTD compared to bvFTD patients implying to be a valuable tool in distinguishing phFTD from bvFTD. Worse ADL performance and increased behavioural symptoms reported by caregivers in phFTD is remarkable and indicates further research is needed to asses if patient‐based tools are superior to caregiver‐based tools when suspecting phFTD.