bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance on autobiographical memory tests measuring contextual details is impaired in subjective cognitive decline and mild cognitive impairment
Authors: Bruus Anna Elise , Waldemar Gunhild , Vogel Asmus
Published: December 2021

Background

The neuropathological hallmarks of Alzheimer’s disease (AD) occur many years prior to the onset of clinical symptoms. Subjective memory decline can occur during this phase, but no standardized, clinically usable neuropsychological tests are currently able to detect such changes. Autobiographical memory (AM) tests tap a brain network affected in “preclinical” AD. The aim of this study was to investigate whether AM test performance was impaired in persons with Subjective Cognitive Decline (SCD) and in persons with Mild Cognitive Impairment (MCI) and mild dementia due to AD.

Method

We included 17 SCD patients diagnosed according to international SCD criteria, 17 amnestic MCI (aMCI) patients, and 17 patients with mild dementia due to AD. A group of 30 healthy controls was also examined. All participants were ≥ 45 years old and had MMSE scores of ≥ 24. AM was assessed using the Columbia Autobiographical Memory Interview – Short Form (CAMI‐SF) and an instrument, which we named the 3 Events Test. Both measure the specificity of AM and the ability to provide details about personal experiences. We also applied cognitive and neuropsychiatric screening tests and a traditional neuropsychological battery.

Result

For the 3 Events Test, a significant effect of group was found. Post‐hoc testing showed that participants with SCD, aMCI, or mild AD produced significantly fewer contextual details than the healthy controls. An ANOVA also showed a significant effect of group for the CAMI‐SF, and post‐hoc testing showed that the aMCI and mild AD groups were able to answer fewer questions or gave less detailed answers compared to the other groups. The total scores on the CAMI‐SF were lower in the SCD group than in the control group, but the difference was not significant.

Conclusion

AM was compromised in SCD, aMCI, and mild AD, as reflected by lower scores on the 3 Events Test compared to the control group. Thus, AM may be impaired in very early AD – even in the phases where standard episodic memory tests show no decline. AM tests could be useful in the attempt to verify subjective memory problems, and a decline on such a test could indicate later cognitive decline.
Comparison of language and narrative features of individuals among amnestic mild cognitive impairment and healthy adults
Authors: Karali Fenise Selin , MAVIS Ilknur , Cinar Nilgun
Published: December 2021

Background

Mild Cognitive Impairment (MCI) is a stage between normal aging and dementia. Even though individuals have some decline in cognition due to normal aging, preserved daily life functioning skills is the main distinction between dementia and MCI. Individuals with MCI experience mild impairments in memory, language and judgement.

MCI is classified in two subtypes: one is amnestic MCI which is characterized by memory impairment, the other one is non‐amnestic MCI in which other cognitive domains are impaired. Individuals with amnestic MCI (aMCI) are at increased risk of developing Alzheimer disease (AD). The purpose of this study is to determine the language and narration skills of individuals with aMCI and to compare their scores with healthy participants.

Method

For this purpose, the Test Your Memory – Turkish Version (TYM‐TR), the Turkish Picture Naming Test (T‐RAT), the Aphasia Language Assessment Test (ADD) Repetition Subtest, the Turkish Nonword Repetition Test (TAST) were administered to 60 participants between the ages of 60‐85, 30 with aMCI and 30 healthy individuals. Pyramid and Palm Trees Test (PPTT) and the Multilingual Assessment Instrument for Narratives (MAIN‐TR) Dog Story Retelling tasks were also administered.

Result

After the distribution of the data was examined, those with normal distribution were compared between the groups with independent samples T test and the data that did not show a normal distribution were calculated using non‐parametric Mann Whitney‐U. As a result of the statistical analysis, it was determined that nonword repetition differed significantly between the groups. As for macrostructures, it was determined that there was a difference between the groups in terms of story structure and comprehension. As for the other parameters, even though the average of healthy individuals was higher, no significant difference was found between the groups.

Conclusion

This study is the first on the language and narrative skills of the participants with aMCI in Turkish, and it is thought that it will shed light on the language skills of individuals with aMCI during the neurodegeneration process. Determining the changes in language skills is very important in setting goals for Language and Speech Therapy.
Psychosocial effects of the humanoid socially assistive robot Coach Pepper on informal caregivers of people with dementia: A mixed‐methods study
Authors: Zuschnegg Julia , Schüssler Sandra , Paletta Lucas , Voithofer Claudia , Lodron Gerald , Orgel Thomas , Russegger Silvia , Schneeberger Michael , Fellner Maria , Steiner Josef , Pansy‐Resch Sandra , Holter Magdalena , Prodromou Dimitrios , Brunsch Sebastian , Carnevale Lorenzo , Lammer Lara , Koini Marisa
Published: December 2021

Background

Dementia care is largely provided by informal caregivers, which can present significant challenges and increase caregivers’ burden. Humanoid socially assistive robots (SARs) have the potential to provide assistance, but evidence is missing. The aim was to explore the psychosocial effects of Coach Pepper (humanoid SAR system “AMIGO” combined with a tablet PC‐based dementia training) versus an exclusive tablet PC‐based dementia training on informal caregivers of people with dementia living at home (as well as their experiences).

Method

A randomized controlled trial with a complementary qualitative part was performed (May 2019‐March 2020). 32 informal caregivers of people with dementia living at home participated in the study. The intervention group received Coach Pepper and the control group received only the tablet‐based dementia training. The duration of the intervention was three weeks per household. Data was collected at baseline and after the intervention by standardized questionnaires for caregiver burden (primary outcome), quality of life, depressive symptoms and affect. Additionally, interviews about caregivers’ experiences were conducted in the intervention group.

Result

Participants were on average 58.2 (±12.5) years old and predominantly female (68.8%). Quality of life, depressive symptoms and affect demonstrated no significant differences regarding between‐group mean changes, neither did caregivers’ burden, which showed decreasing tendencies of burden in the intervention and control group (Zarit Burden Interview, ‐2.7±8.7 vs. ‐4.4±6.4, p=0.2552). Qualitative findings revealed that participants had positive attitudes regarding Coach Pepper and experienced it as neutral in terms of burden. Some stated that Coach Pepper provided relief/more free time by entertaining the persons with dementia. However, some participants stated that they had to invest additional time until the person with dementia was able to engage with Coach Pepper and that its usability should be improved in certain areas (e.g., communication) to constitute more support for caregivers.

Conclusion

Coach Pepper had no significant psychosocial effects on informal caregivers of people with dementia. Qualitative findings demonstrated the participants' positive attitudes but highlighted a need for improvement regarding its usability. This study contributes to the development/modification of Coach Pepper based on caregivers’ needs in dementia care.
Web application for single‐case AD subtyping and staging based on SuStaIn model
Authors: Archetti Damiano , Oxtoby Neil P. , Alexander Daniel C. , Redolfi Alberto
Published: December 2021

Background

In recent years, statistical and machine learning algorithms allowed advancements in many fields of healthcare research, but such methods are still mostly used by technical experts. Their implementation in user‐friendly software/web interfaces is fundamental for their broader adoption by patient‐facing physicians.

Method

A validated SuStaIn (Young et al, 2019, https://doi.org/10.1038/s41467-018-05892-0) model for atrophy patterns in Alzheimer’s Disease (AD) was used as core for a web application. The model was trained using volumes of relevant brain regions of 1031 subjects from the Alzheimer’s Disease Neuroimaging Initiative and validated using 731 subjects from the OASIS, PharmaCog and ViTA Cohorts. Biomarkers used to train and validate the model were corrected against the effects of age, sex, education, APOE genotype and total intracranial volume (TIV). The model was exploited in the web application for single‐case scenarios. The user is required to input age and sex of the subject and upload an MRI scan which is processed with Freesurfer 5.3 to extract relevant brain volumes. Volumes are corrected against the effects of sex, age and TIV and converted into z‐scores used to compute the most likely among the three subtypes defined by the model and stage the subject on the relative z‐scores progression sequence. Results are summarized in a report (Fig. 1) and sent to the user via e‐mail. The web application skips the correction against education and APOE genotype as these factors may be unavailable and their influence on volumes should be minor. The validity of the different correction procedure was tested by subtyping and staging 50 subjects from the training set using the web application. Outputs were compared with the results of the validated model.

Result

The web application was built and deployed on the neuGRID platform, and it is available at https://www.neugrid2.eu/index.php/ml-tools/sustain/. All subjects tested on the web application were assigned the same subtype as the validated model, although an average difference equal to 2.2 positions was observed for the staging.

Conclusion

This web application implementing a SuStaIn model for AD atrophy subtypes represents a first example of advanced data‐driven algorithms implemented in a user‐friendly tool usable by clinicians in daily practice.
BDNF shown to partially mediate greater verbal learning performances in women as compared to men in a cohort enriched with risk for Alzheimer’s disease
Authors: Edmunds Kyle J. , Mamlouk Gabriella M. , Okonkwo Ozioma C. , Rogers Christine C.
Published: December 2021

Background

It is established that the sex‐based prevalence of Alzheimer’s disease (AD) is greater in women, though the mechanisms underlying this difference are not well understood. Furthermore, in cognitively normal adults, women consistently score higher than men in verbal learning ability, a primary domain of cognitive function sensitive to decline from AD progression. The sex‐specific mechanisms of action of brain‐derived neurotrophic factor (BDNF), a growth factor important for memory and long‐term brain health, may explain observed sex‐based differences in cognitive decline. The purpose of this study was to investigate whether sex‐based differences in verbal learning and memory (VLM) are mediated by BDNF expression in a cohort of cognitively normal adults at risk for AD.

Method

Wisconsin Registry for Alzheimer’s Prevention (WRAP) participants (n=201, age 63.81±6.04, 66.2% women, 65.7% family history of AD, 38% APOE‐ε4 carriers, without known cognitive decline) underwent the Rey Auditory Verbal Learning Test (RAVLT), trials 3‐5 and delayed recall, to assess VLM function. BDNF serum levels were measured using Human BDNF Quatikine Immunoassay DBD00 from R&D Systems. Mediation analysis was performed using the Hayes and Preacher macro for IBM SPSS, adjusting for age, time between variable collection, APOE‐ε4 status, parental AD history, and hippocampal volume.

Result

Regression models indicated significantly higher levels of BDNF in women (F(6,191)=2.38, p=0.031, R2 =0.07, β=‐2280.89, t(191)=‐2.52). Women were found to have significantly higher VLM scores (F(6,191)=7.22, p<0.0001, R2=0.18, β=‐0.68, t(191)=‐4.58). Greater BDNF levels indicated higher VLM scores (β<0.00, t(190)=2.49, p=0.014). Controlling for BDNF as a mediator attenuated the effect of sex on VLM, indicating partial mediation from BDNF (β=‐0.61, t(190)=‐4.12, p=0001).

Conclusion

This study shows that BDNF level partially mediates the higher scores of women in VLM in a cohort of cognitively normal adults at‐risk for AD, suggesting that sex‐specific differences in BDNF expression may partially explain the differing prevalence of AD between the sexes. However, this difference is likely due to many additional factors, and it is still unknown whether this relationship persists throughout clinical AD. Research is needed on the relationship between BDNF, sex, and VLM in individuals with cognitive impairment, as well as the direct interactions between these factors.
Associations between low‐value care treatments and patient‐centered outcomes of people with dementia: A cross‐sectional analysis
Authors: Platen Moritz , Raedke Anika , Wucherer Diana , Thyrian Jochen René , Mohr Wiebke , Scharf Annelie , Mühlichen Franka , Hoffmann Wolfgang , Michalowsky Bernhard
Published: December 2021

Background

Rapidly increasing healthcare expenditures are a global healthcare challenge. Parts of these costs are caused by an overtreatment of patients or low‐value care (LvC), which is defined as care unlikely to provide a benefit to the patient or likely to provide harm. However, there is currently a lack of evidence about the prevalence of LvC and its association with patient‐reported outcomes in people living with dementia (PwD).

Method

The analysis was based on the baseline data of the DelpHi‐trial, including 516 community‐dwelling PwD. LvC were identified by a systematic review of dementia‐specific evidence‐based guidelines, "do not do" recommendations of initiatives, like “Choosing Wiseley”, and lists of inappropriate medication for the elderly. The association of LvC treatments with health‐related quality of life (HRQol), assessed by using the SF‐12 and the Quality of life in Alzheimer´s diseases, and hospitalization were analyzed using multiple regression models.

Result

The study revealed that 159 PwD (31 %) received at least one LvC treatment. They had, on average, less cognitive impairment and less functional impairment than those without LvC. PwD who received LvC had a lower quality of life (b=‐0.08; CI95% ‐0.14 – ‐0.02) and were more likely to be hospitalized (OR=2.11; CI95% 1.30 – 3.41). The lower HRQol was attributed to the measured sedatives and hypnotics (B=‐0.21; CI95% ‐0.34 – ‐0.08). The higher odds for hospitalization could be caused by antidepressants (OR=2.86; CI95% 1.10 – 7.46) and antihypertensive drugs (OR=4.09; CI95% 1.20 – 13.92).

Conclusion

LvC could reduce patients' HRQoL and increase the risk of hospitalization. More research is needed to evaluate if innovative approaches, like digital health applications, are useful to identify and reduce LvC within primary care and if this could improve PwD HRQoL and reduce hospitalizations.
Developing a consensus protocol for genetic testing in frontotemporal dementia
Authors: Greaves Caroline V , Lahiri Nayana , Rohrer Jonathan D ,   The Genetic Frontotemporal Dementia Initiative (GENFI) and UK Predictive Testing Consortium
Published: December 2021

Background

Frontotemporal dementia (FTD) is genetic in around 30% of people. The aim of the study was to develop a consensus protocol for genetic testing in FTD.

Methods

A Delphi methodology was used to achieve consensus recommendations from an international consortium of FTD and neurogenetics specialists. Participants were presented with a number of scenarios involving an asymptomatic individual from a family with a history of FTD but no known genetic mutation, who is requesting predictive testing. Consensus was defined as a recommendation being selected by >80% of respondents.

Results

1) If an affected relative is alive and able to consent for diagnostic testing, a sample should be taken to ascertain whether there is a genetic form of FTD in the family before the asymptomatic individual can pursue predictive testing. 2) In the case where the affected relative is alive but unable to consent to diagnostic testing, experts decided that a blood or saliva sample could be taken if possible, and with the family’s agreement diagnostic testing could be performed to ascertain whether a mutation is present prior to predictive testing. 3) When there is no living affected relative but a sample of DNA or tissue has been stored, experts agreed that diagnostic testing should be performed on the sample, independent of family history, prior to offering predictive testing. 4) In the case where there is no living relative and no stored DNA or tissue but there is known pathology in a deceased family member that is pathognomonic for a specific genetic form of FTD, the consensus was to perform predictive testing based on that pathology. 5) Where there is no stored sample available, experts were in agreement that predictive testing should not be offered.

Conclusions

This revised protocol will provide guidance to clinicians for FTD‐specific genetic testing.
Pattern of progression in MAPT‐related frontotemporal dementia: Results from the GENFI study
Authors: Todd Emily G , Peakman Georgia , Cash David M , Convery Rhian S , Russell Lucy L , Thomas David L , van Swieten John C , Jiskoot Lize C. , Seelaar Harro , Borroni Barbara , Galimberti Daniela , Sanchez‐Valle Raquel , Laforce Robert , Moreno Fermin , Synofzik Matthis , Graff Caroline , Masellis Mario , Tartaglia Maria Carmela , Rowe James B , Vandenberghe Rik , Finger Elizabeth , Tagliavini Fabrizio , de Mendonca Alexandre , Santana Isabel , Butler Christopher , Ducharme Simon , Gerhard Alexander , Danek Adrian , Levin Johannes , Otto Markus , Sorbi Sandro , Le Ber Isabelle , Pasquier Florence , Rohrer Jonathan D , Bocchetta Martina ,   Genetic Frontotemporal Dementia Initiative (GENFI)
Published: December 2021

Background

Mutations in MAPT are associated with frontotemporal dementia (FTD), but little is known about the progression in its early stages. We aimed at identifying the presence of early brain changes in MAPT mutation carriers.

Method

We included 3T MRIs from 84 MAPT carriers [27 symptomatic: mean(SD) age 58(8) years; 57 presymptomatic: 40(11) years] from the Genetic FTD Initiative (GENFI) and from 77 age‐matched non‐carrier healthy controls (44(14) years). Based on their expected years to symptom onset (EYO), we divided the presymptomatic carriers into early (n=35, <‐10 years) and late (n=22, >‐10 years) groups.

First, we performed voxel‐based morphometry (VBM) comparing 24 symptomatic carriers with 32 controls to identify the regions of interest (ROIs) which were atrophic in the symptomatic stage of MAPT. We then used automated and manual segmentations to extract these ROI volumes in all carriers. To remove the effect of age, gender, total intracranial volume and scanner type, we transformed the volumes into w‐scores, considering the controls as the reference group. A w‐score of <‐1.28 (corresponding to the 10th percentile) was considered abnormal.

Result

From the VBM we identified seven structures significantly atrophic in symptomatic carriers: the nucleus accumbens, amygdala, hippocampus, orbitofrontal cortex, temporal pole, anterior insula and hypothalamus.

The percentage of early presymptomatic carriers with abnormal w‐scores was 14% for nucleus accumbens and hippocampus, and 20% orbitofrontal cortex. In the late group, 36% showed abnormal amygdala and temporal pole, 27% abnormal hippocampus, 32% abnormal anterior insula and 9% abnormal hypothalamus. In the symptomatic group, the percentages were higher: nucleus accumbens (41%), amygdala, hippocampus and temporal pole (85%), orbitofrontal cortex (56%), anterior insula (93%) and hypothalamus (48%).

Conclusion

Abnormal limbic regions are a frequent feature in presymptomatic MAPT carriers, showing early structural changes before symptom onset. Further investigations on the associated cognitive and white matter changes are ongoing.
Active diagnostics of dementia in the inland region of Portugal
Authors: Marques Ermelinda Maria Bernardo G , Paiva Teresa , Paulino Manuel , Corte Agostinha ,   NEUROQUALYFAM Group
Published: December 2021

Background

According to Alzheimer Europe (2019), it is estimated that in 2018, there were 8,885,101 people with dementia in Europe (EU‐28), with a prevalence of 1.73%. In Portugal, it is estimated that this figure is 193,516, with a prevalence of 1.88%, surpassing the European trend, since it is expected to almost double the number of cases in 2050 (346,905), reflecting the significant increase of people over 70 years and, specifically over 85. The OECD's “Health at a Glance 2020” report indicates that Alzheimer's and other dementia accounted for 5% of all deaths in 2017.

Thus, it becomes relevant to study the magnitude of this problem also at the local level.

This study aims to identify and characterize people with dementia in a region of the inland region of Portugal. It is assumed as the first stage of a more comprehensive study on the quality of life of the person with dementia and his/her family, within the framework of the NEUROQUALYFAM Project (0541_NEURO_QUALYFAM_6_E).

Method

This is a cross‐sectional descriptive epidemiological study of people with dementia. The data, provided by health services, refer to the active diagnoses of the disease, according to the International Classification of Primary Health Care ‐ ICPC‐2 (P70 ‐ Dementia) and do not allow to trace any of the individuals.

Result

The total number of people with active diagnosis of Dementia (P70) was in 2019, around 1603 cases, with an increase of 363 cases between 2014 and 2019. The proportion of active diagnoses in the resident population was 1.13%, with higher values in women (0.80% versus 0.33% in men). Most active diagnoses (95.51%) are from people aged 65 years or older, also reflecting the results a higher proportion in the higher age groups, namely 25.02% in the 80–84‐year‐old group and 43.54% in the 85‐year‐old group.

Conclusion

The identification and characterization of people with dementia, in the geographic area under study, will now allow the development of the study of the quality of life of these people and their families so that it is possible to implement more specific and targeted strategies for this target population.
Markers of periodontal disease and cognitive decline in a diverse, older cohort
Authors: Nikitin Benjamin , Bahorik Amber L , Mcevoy Claire T , Yaffe Kristine
Published: December 2021

Background

Prior studies have reported associations between periodontitis, as a proxy for inflammation, and increased risk of cognitive decline and dementia, but findings for specific markers of periodontal disease (PDD) have been inconsistent with the few longitudinal studies in diverse cohorts. The goal of this study was to assess whether measures of PDD were associated with subsequent cognitive decline in a cohort of older Black and white adults.

Method

We studied 967 Black and white adults, aged 70‐79 at baseline (51.8% female and 32.8% Black), enrolled in the Health, Aging and Body Composition study. Participants received a periodontal exam in year 2 which assessed indicators of PDD: gingival index (a rating of gingival inflammation), mean attachment loss, and mean pocket probing depth. Cognitive testing was repeated at baseline, years 3, 5, 8, 10, and 11, and included the Modified Mini‐Mental State (3MS) Examination and the Digit Symbol Substitution Test (DSST). We evaluated the association between PDD, categorized as tertiles, and cognitive decline over 11 years of follow‐up with linear mixed‐effects models.

Result

In unadjusted models, higher gingival index was associated with greater decline on 3MS (high vs. low gingival index β = ‐0.27, 95% CI ‐0.48 to ‐0.05) but not DSST. This relationship remained significant after adjusting for race, sex, education, and socioeconomic status (β = ‐0.26, 95% CI ‐0.48 to ‐0.04). Models stratified by race suggest that this association was stronger among older Black adults (Black: β = ‐0.44, 95% CI ‐0.81 to ‐0.06; white: β = ‐0.13, 95% CI ‐0.40 to ‐0.12). Mean attachment loss and mean pocket probing depth were not consistently associated with cognitive decline.

Conclusion

Gingival index was associated with worse decline in global cognition among Black and white older adults. Further work is necessary to understand other measures of poor oral health as markers of cognitive aging in diverse populations.
Longitudinal hippocampal atrophy in hippocampal sclerosis of aging vs. Alzheimer’s disease
Authors: Li Janice X. , Nguyen Hannah L. , Woodworth Davis C. , Sajjadi S. Ahmad
Published: December 2021

Background

Hippocampal sclerosis of aging (HS) is a common degenerative neuropathology in older individuals and is strongly associated with dementia. HS is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy and how it relates with stages of cognitive impairment in individuals with HS. We performed a longitudinal case‐series study of hippocampal atrophy and its progression in participants with HS at autopsy compared with matched participants with Alzheimer’s disease (AD) and those without HS or AD to better understand the longitudinal pattern of hippocampal atrophy in HS.

Methods

We used data from Alzheimer’s Disease Neuroimaging Initiative (ADNI‐1, http://adni.loni.usc.edu/) participants with both 3D‐T1w MRIs and autopsy data. Of 47 total participants, 6 had HS. 12 comparison cases were matched by age, sex, and education: 6 with AD, and 6 with neither HS nor AD (No‐HS/AD). We calculated total hippocampal volume using FreeSurfer v6.0 (https://surfer.nmr.mgh.harvard.edu/fswiki/LongitudinalHippocampalSubfields). We plotted hippocampal volumes with respect to age labeled by cognitive status, and compared average volumes and slopes using paired T‐tests.

Results

Participant characteristics are shown in Table‐1. Three HS participants also had AD. All except one HS participants had lower hippocampal volumes compared to the matched AD and No‐HS/AD participants (Figure‐1). HS3 participant maintained a high hippocampal volume and normal cognition throughout follow‐up. When excluding participants with normal cognition at the time of imaging (HS3, N5), paired T‐tests for average hippocampal volume trended towards significance (HSvsAD P=0.060, HSvsNo‐HS/AD P=0.12), but there were no significant differences in slopes of volume change with age (Figure‐2).

Conclusion

The results of this case‐series suggest that individuals with HS have MRI detectable smaller hippocampi than individuals with AD or other pathologies at corresponding stages of cognitive impairment. Our findings also suggest that hippocampal atrophy may begin several years before dementia onset in individuals with HS, supporting the potential utility of hippocampal atrophy as an early biomarker for HS.
Cognitive decline in possible vascular cognitive impairment (VCI): Does the form of vascular brain injury matter?
Authors: Boomsma Jooske , Exalto Lieza G. , Barkhof Frederik , Leeuwis Anna E. , Prins Niels D. , Scheltens Philip , Teunissen Charlotte E. , Weinstein Henry C. , Biessels Geert Jan , van der Flier Wiesje M ,   TRACE‐VCI study group
Published: December 2021

Background

Patients presenting at a memory clinic with possible VCI include a heterogeneous population in terms of cognitive profile, vascular brain injury and prognosis. Little is known about the trajectories of cognitive decline on cognitive test performance in relation to the different forms of vascular brain injury.

Method

We included 474 memory clinic patients(age 68(±8.2) years, 44% female, mean MMSE 25.9(±2.9), 212(44.7%) patients with dementia) from the prospective TRACE‐VCI cohort study with possible VCI; cognitive complaints and vascular brain injury on MRI. We assessed cognitive functioning at baseline and follow‐up(mean follow‐up time 2.5(±1.4) years, total of 1176 neuropsychological tests) including the Rey Auditory Verbal Learning Test(RAVLT) immediate and delayed recall(memory), the Trail Making Test(TMT) A and B(attention and executive functioning, respectively), category fluency(language) and MMSE. Linear mixed models were used to evaluate the effect of different forms of vascular brain injury on cognitive decline. Models included(dichotomized) terms for vascular brain injury(infarct(s), lacune(s), white matter hyperintensities(WMH), microbleed(s)), time and vascular brain injury*time. All models were adjusted for sex, age, diagnosis (dementia versus no dementia), education and medial temporal lobe atrophy(MTA) score(dichotomized as ≥1.5). Also, the models were evaluated in patients with a positive(+CSF‐AD) and negative(‐CSF‐AD) biomarker CSF Alzheimer profile.

Result

Vascular brain injury(multiple forms in one patient possible) consisted of infarct(s) in 54(11.4%), lacune(s) in 108(22.8%), moderate/severe WMH in 212(44.7%) and microbleed(s) in 203(42.8%) patients. In 164(54.3%) patients the MTA score was ≥1.5. We found no association between any form of vascular brain injury and baseline cognition. Infarct(s) showed an association with worsening on the TMTB(β;30.19,p=.00), especially in patients with a –CSF‐AD(β;65.93,p=.00). This effect was not found in patients with a +CSF‐AD(β;‐25.24,p=.18). Lacune(s) were associated with a rate of decline in immediate memory(β;1.62), delayed recall(β;.33), category fluency(β;.44) and MMSE(β;.46;all p<0.05). Infarct(s) were associated with a slower rate of decline on category fluency(β;.96,p=.01). We found no association between WMH, microbleed(s) and rate of cognitive decline.

Conclusion

In patients with possible VCI, infarct(s) were associated with steeper decline in executive functioning, especially in patients with a –CSF‐AD. Counterintuitively, the presence of lacune(s) and infarct(s) predisposed for a more favorable trajectory in memory.
Remote identification of MCI using self‐ and study partner‐report subjective cognitive decline in the Brain Health Registry
Authors: Nosheny Rachel L , Jin Chengshi , Banh Timothy , Ashford Miriam T. , Camacho Monica R , Mackin R Scott , Truran‐Sacrey Diana , Flenniken Derek , Neuhaus John
Published: December 2021

Background

Efficient identification of older adults with Mild Cognitive Impairment (MCI), including MCI due to AD, is a pressing challenge. Remote methods to accurately identify older adults with MCI are a promising approach. Subjective cognitive decline (SCD), reported by individuals and their study partners, can be efficiently collected remotely.

Methods

In 1286 older adults in the Brain Health Registry (BHR, Table 1), using logistic regression, we determined the accuracy of online self‐report mood (Geriatric Depression Scale Short Form, GDS), family history of AD, Everyday Cognition Scale (ECog) as a measure of SCD, and Cogstate Brief Battery one card learning (OCL) accuray to distinguish (1) Cognitively‐unimpaired (CU) from MCI, and (2) CU from b‐amyloid (Ab)+ MCI. In a subset of 289 participants with enrolled study partners, we measured the contribution of study partner‐report SCD to predicting diagnostic category, and the correlation between self‐ and study partner‐report SCD. Models covaried for age, gender, and education level.

Results

Self‐ and study partner‐report SCD scores were moderately correlated (r=0.44); associations between the two measures were significantly lower in participants with higher GDS scores, indicating more depressive symptoms (p=0.03). Models including self‐ and study partner‐report SCD and Cogstate OCL scores had the highest accuracy for distinguishing CU from all MCI, as well as CU from Ab+ MCI (AUC=0.90 for CU vs MCI; AUC=0.93 for CU vs Ab+ MCI). Models excluding study partner‐report SCD had moderate accuracy at diagnostic classification (AUC=0.81 for CU vs MCI; AUC=0.83 for CU vs Ab+ MCI). Models excluding all SCD measures, and instead relying on OCL accuracy scores, had lower accuracy (AUC=0.73 for CU vs MCI; AUC=0.76 for CU vs Ab+ MCI). Model outputs are summarized in Table 2.

Conclusions

Remotely‐collected self‐ and study partner‐report SCD accurately distinguish CU from MCI, as well as CU from biomarker positive MCI. SCD measures perform well in identifying MCI, even in the absence of objective cognitive measures. Results support utilization of remote SCD measures to identify older adults for prodromal AD clinical trials, and who are suitable candidates to receive future anti‐amyloid therapeutics.
Associations between cerebrospinal fluid markers of neuroinflammation and longitudinal measurements of white matter lesions
Authors: Gertje Eske Christiane , Janelidze Shorena , van Westen Danielle , Cullen Nicholas , Palmqvist Sebastian , Hansson Oskar , Mattsson‐Carlgren Niklas
Published: December 2021

Background

The interplay between neuroinflammation and small vessel disease in the early stages of neurodegenerative disease is unclear. Here, we tested the association between cerebrospinal fluid (CSF) levels of biomarkers reflecting inflammatory processes and white matter lesion (WML) volume over time.

Method

We included 582 cognitively unimpaired (CU) elderly and 279 patients with mild cognitive impairment (MCI). CSF samples were analyzed for interleukin (IL)–6, IL‐7, IL‐8, IL‐15, IL‐16, interferon‐gamma induced protein‐10 (IP‐10), monocyte chemoattractant protein 1 (MCP‐1), intercellular adhesion molecule 1(ICAM‐1), vascular adhesion molecule 1 (VCAM‐1), placental growth factor (PlGF), and fms‐related tyrosine kinase 1 (sFlt‐1) as well as vascular endothelial growth factor (VEGF). WML volumes were measured at baseline, and at 2, 4 and 6 years. Analyses were adjusted for Aβ status, age and gender.

Result

In CU, lower levels of PlGF (β=‐0.02, p=0.027) were associated with increasing WML burden over time. However, in MCI lower levels of PlGF (β=‐0.05, p<0.001), IL‐16 (β=‐0.04, p=0.010), VEGF (β=‐0.03, p=0.012), IL‐6 (β=‐0.04, p=0.005), IL‐8 (β=‐0.03, p=0.016) and MCP‐1 (β=‐0.03, p=0.012), as well as higher levels of sFlt‐1 (β=‐0.03, p=0.034) were associated with longitudinal increase in WML.

Conclusion

CSF markers mediating angiogenesis, such as PlGF and VEGF, are associated with longitudinal WML volume changes, especially in individuals with MCI.
Racial/ethnic disparities in new and persistent cholinesterase inhibitors treatment in Alzheimer’s disease
Authors: Zhu Carolyn W , Neugroschl Judith A , Sano Mary
Published: December 2021

Background

Racial/ethnic minorities are less likely to use anti‐dementia medications and less likely to participate in dementia studies. It is unclear if treatment disparities remain in those who participate in longitudinal research at Alzheimer’s Disease Centers (ADCs).

Methods

Data were drawn from the National Alzheimer's Coordinating Center Uniform Data Set (9/2005‐11/2019). Baseline inclusion criteria: ≥65yo, etiology of AD, and CDR<3. Sample included Non‐Hispanic white, Non‐Hispanic Black, or Hispanic participants with ≥1 follow‐up. Main outcomes: (1) any new Acetylcholinesterase (AChEI) treatment during follow‐up, (2) persistence of treatment measured by proportion of follow‐up visits reporting AChEI use, categorized into: intermittent (<50% follow‐ups), persistent (≥50% follow‐ups), and always treated. Differences by race/ethnicity were estimated using logistic or ordered logistic regression models, controlling for participant clinical and demographic variables.

Results

Sample included 5,866 white, 918 Black, and 608 Hispanic participants. Compare to the treated, those who were untreated at baseline were older, more likely to be female, lived alone, more likely to have AD (vs. MCI), with better clinical profiles (better CDR, FAQ, NPIQ, MMSE, lower rate of hypertension and diabetes). Among baseline untreated, average age=77.1±7.0, 55% female, education=14.7±3.8 years, MMSE=24.4±4.7. 51% AD. The proportion of participants with CDR=0.5, 1, 2 was 66%, 25%, and 6% respectively. 47% were referred by a clinical professional. Average follow‐up=3.9±2.2 years. 83% had a spouse/partner or child as co‐participant. Etiology remained AD for 85% of follow‐up visits. Any new AChEI treatment during follow‐up was lower among Blacks (33.7%) and Hispanics (41.4%) compared to whites (45.8%) (p<0.001). After controlling for participant characteristics, adjusted odds of any new AChEI treatment remained lower for Blacks (OR=0.707±0.068) and Hispanics (OR=0.813±0.083, both p<0.05) compared to whites. Unadjusted differences in persistence of treatment were not statistically significant (13.6% intermittent, 28,8% persistence, 57.6% always treated). However, adjusted differences in persistence of treatment was significantly lower for Blacks (OR=0.827±0.090) and Hispanics (OR=0.785±0.081, both p<0.05) compared to whites.

Conclusion

Racial/ethnic minorities had lower rates of AChEI treatment at study enrollment. Disparities in AChEI treatment persisted even though individuals were followed in ADCs over time and remained significant after adjusting for clinical and demographic variables.
Deep Residual Inception Encoded‐Decoder Neural Network for amyloid PET harmonization
Authors: Shah Jay , Ghisays Valentina , Luo Ji , Chen Yinghua , Lee Wendy , Li Baoxin , Benzinger Tammie L.S. , Reiman Eric M. , Chen Kewei , Su Yi , Wu Teresa
Published: December 2021

Background

Amyloid PET is an in vivo technology to visualize and quantify beta‐amyloid deposition in the brain. However, the use of multiple amyloid tracers with varied characteristics compounded by processing variabilities poses significant challenges to interpret or combine results from cross‐center studies, and to define common positivity threshold. In this research, we developed an encoder‐decoder based deep model as a harmonization strategy to render imputed amyloid PET images of one amyloid tracer to the images of another.

Method

91 PiB‐florbetapir (FBP) image pairs from the Open Access Series of Imaging Studies (OASIS) were processed using established pipelines to extract regional standard uptake value ratios (SUVRs), mean cortical SUVRs (mcSUVRs), and SUVR images. Residual Inception Encoder‐Decoder Neural Network (RIED‐Net) was implemented to learn the nonlinear mappings from the image pairs in 2D using encoding‐decoding architecture in conjunction with residual inception blocks and generating imputed images. A 10‐fold cross‐validation was implemented on axial, coronal and sagittal views separately to generate imputed PiB SUVR imaging from FBP data. The average imputed PiB image from all three views was used for performance evaluation. Correlation was evaluated between the imputed vs. real PiB SUVR image voxel‐wise, and between the virtual PiB mcSUVR derived from imputed PiB vs. the real PiB mcSUVR. The trained RIED‐Net model was also applied to an independent dataset with 46 subjects from www.gaain.org/centiloid‐project, and the same metric was used to assess performance.

Result

The imputed PiB SUVR images were visually more similar to real PiB SUVR images than FBP. Voxel‐wise correlation improved from 0.89 between PiB and FBP to 0.95 between the synthetic and real PiB SUVR image (p<0.0001) in the cross‐validation. The agreement of mcSUVR improved from r=0.91 to r=0.96 (p<0.0001) in the cross‐validation dataset and from r=0.92 to r=0.96 (p<0.001) in the independent dataset.

Conclusion

We proposed a novel encoder‐decoder based deep model for synthetic imaging. The model discovered the voxel‐wise nonlinear associations between the input images and the output images which significantly improved agreements of amyloid burden measurements from different tracers. The result was further confirmed in an independent dataset demonstrating the generalizability.
Spatial covariance structure of tau‐PET changes more than Aβ‐PET across disease stages
Authors: Chen Gengsheng
Published: December 2021

Background

Alzheimer disease (AD) has a long preclinical phase with pathophysiological changes such as β‐amyloid (Aβ) accumulation in early stages followed by tau deposition. Graph theory may provide additional insights into the disease processes underlying patterns of Aβ and tau deposition (Pereira et al., 2018; Hoenig,2018). This project uses graph theory to study the spatial covariance structure of Aβ‐PET and tau‐PET changes across disease stages.

Method

This study includes 254 cognitively normal participants (Clinical Dementia Rating™ (CDR™) =0) and 41 impaired participants (CDR>0) from the Washington University Knight Alzheimer Disease Research Center (ADRC, Funding: P50AG005681; P01AG003991; P01AG026276), who underwent MRI, Aβ‐PET 18F‐AV45, and tau‐PET (18F‐AV1451). Regions of interest were defined using the Freesurfer Desikin atlas. Regional Aβ and tau standardized uptake value ratios (SUVRs) were adjusted by gender and age, and used to generate Pearson correlation matrix. Aβ and tau spatial covariance structure can be built as a collection of nodes representing the mean SUVR values from different brain regions, connected by edges representing correlated deposition quantity. BRAPH toolbox (Mijalkov, 2017) were used to calculate Binary Undirected Density (BUD) graph measures. To test for significant differences between these two groups, BRAPH performs non‐parametric permutation tests. Global graph theory measures (global and local efficiency, and modularity) are used to assess the spatial covariance structure of Aβ‐PET and tau‐PET changes.

Result

No significant difference between the CDR=0 and CDR>0 groups was observed for the global measures generated from the Aβ‐PET data (Table 1 and Figure 1A‐C). However, there were significant differences between the two groups for the global measures generated from the tau‐PET data (Table 1 and Figure 1D‐F). The global and local efficiency were lower in the CDR>0 group (p=0.003 and p=0.018, respectively) indicating a higher global and local path length in the covariance structure. Moreover, the modularity was lower (p=0.005) for CDR>0 group, indicating lower fragmentation between regions in this group.

Conclusion

Changes in spatial correlation associated with conversion to clinical impairment are happening in the tau pattern. These spatial covariance structure changes need further evaluation to assess their utility as a biomarker of disease progression in the preclinical phase of AD.
Training of trainers in the GI‐mhGAP dementia module: National training experience in Mexico
Authors: Astudillo‐García Claudia Iveth , Xochihua‐Tlecuitl Tonatiuh , Velásquez José Javier Mendoza , López‐Montoya Alejandra , Austria‐Corrales Fernando
Published: December 2021

Background

The GI‐mhGAP (WHO) is an evidence‐based clinical guideline for the assessment and management of mental, neurological and substance use disorders (MNS) in non‐specialist health settings, which aims to improve capacity for the identification, diagnosis, management and treatment of people with MNS disorders. In Mexico, a national network of facilitators is being established to train non‐specialist mental health providers at the first level of care. Therefore, the aim of this paper is to present how participants perceive themselves in the assessment, management and follow‐up of people with dementia, as well as to provide a replication of this course to primary care personnel.

Method

The sample consisted of 651 participants (doctors, psychologists, nurses and social workers) who were in the virtual training course for facilitators in the GI‐mhGAP given between September‐November 2020, and completed the digital feedback form. Responses were aggregated in a database and analysed using the 'topicmodel' (Grün & Hornik, 2011) and 'tidytext' in R (R Core Team, 2020).

Results

The sample consisted of 474 (72.81%) women and 177 (27.19%) men, with a mean age of 39.9 (SD=8.13). Regarding the perceived self‐efficacy for the assessment of the condition in their daily practice 70.04% (n=456) felt confident to do it, 63.75% (n=415) felt confident to manage the condition; but only half of them felt confident to train other professionals (54.84%, n=357). The results of the semantic analysis reflect the importance of providing psychoeducation to caregivers and family members, as well as training in assessment based on the identification of symptoms for proper diagnosis. It highlights the need for more training on pharmacological treatment, extending its duration and reducing technical problems with the platform, as well as having more examples and clinical cases.

Conclusion

The trained facilitators feel more self‐efficient in identifying and managing the condition in their daily practice, but report the need for further training to be able to replicate the dementia module in primary care providers.
Plasma Aβ1–42 dominantly predicts cognitive decline
Authors: Yang Shieh‐Yueh , Liu H.C.
Published: December 2021

Background

In populations at‐risk for developing dementia, such as patients with Down’s syndrome, stroke, and amnestic mild cognitive impairment, it is important to be able to predict the progression to dementia or cognitive decline. is important to be able to predict the progression to dementia or cognitive decline. In clinical practice, a convenient examination that can evaluate the progression to dementia or cognitive decline is urgently needed.

Method

Notably, there are limitations in this work. Only five studies are available for this review because such studies are novel.

Result

According to this review, plasma Aβ1‐42 possibly plays a more key role in this prediction than Aβ1‐40 or Tau. This implies that abnormal levels of Aβ1‐42 might possibly be a critical trigger of the onset of developing dementia or cognitive decline.

Conclusion

It would be hopeful to stop the development of dementia or delay cognitive decline by eliminating the abnormal changes in the level of plasma Aβ1‐42.
Optimization of biosensor cell lines for the detection of tau seeding competency in human CSF
Authors: Lathuiliere Aurelien , Jo Youhwa , Fan Zhanyun , Hyman Bradley T.
Published: December 2021

Background

The capacity of pathological tau aggregates to recruit and template monomeric tau into misfolded multimers is a major step in the propagation of tau pathology in Alzheimer’s Disease and other tauopathies. Recently, tau seeding activity in postmortem brain tissue was correlated to rate of clinical progression, confirming its relevance in the disease process. If tau seeds could be measured in biofluids, it may be an interesting novel biomarker potentially able to predict disease course. However, current available methods are not sensitive enough to quantify those seeds in the cerebrospinal fluid (CSF).

Method

We generated a series of Förster resonance energy transfer (FRET)‐based biosensor cell lines using rational design of tau bait sequences, linkers, and fluorescent reporter proteins in an attempt to increase assay sensitivity. Transient transfection was used to screen FRET efficiency of novel constructs by flow cytometry. Ultimately, multiple stable cell lines were produced and characterized for their ability to detect tau seeds in human brain lysate and lumbar CSF.

Result

The novel generation of tau biosensor cell lines demonstrated an enhanced sensitivity by more than one order of magnitude as compared to the standard reporter cell line. Tau seeding activity could be measured in less than 100 pg of human brain lysate and in microliters of lumbar CSF.

Conclusion

Optimized FRET‐based biosensor cells can be used to quantify tau seeds in the CSF of live individuals and are currently being implemented to test the hypothesis that seeding capability will vary in different individuals based on the characteristics of tau strains.