bluuebunny/crossref_metadata_2025 huggingface dataset:
Big data analysis of Korea health insurance review and assessment service for treatment cost of dementia and depression from 2014 to 2018
Authors: Eun Hun Jeong , Choi Mal Rye , Kim Hyun Gi
Published: December 2020

Background

Recently, Korea has entered the aging society, and the related dementia and depression are increasing rapidly. Therefore, the purpose of this study was to find out the actual situation by using the Big Data Hub of the Korea Health Insurance Review & Assessment Service to find the data registered in Korea Health Insurance.

Method

Authors visited the Big Data Hub at Korea Health Insurance Review & Assessment Service homepage. After extracting data on the number of patients and medical expenses for 5 years from 2014 to 2018 for dementia and depression in Big Data Homepage, the data were analyzed and statistically verified using Microsoft Excel and IBM SPSS version 23.0. Mann‐Whitney test for hypothesis evaluation applicated.

Result

No. for 5yrs(2014‐2018) : Dementia 929,552.571±809112.0384, Depression 1,434,674.429±1006545.7405 Probability of correct significance, p=0.259. Total Cost for 5yrs : Dementia 3,219,859,523.57±3070117355.004(Korean Won), Depression 566,886,256.29±409089339.917(Korean Won), p=0.209, Expenses excluding insurer contribution applicated for data analysis. Total cost for 5yrs/person : Dementia 2,466.0143±791.06624(US dollar), Depression 334.1757±19.28922(US dollar), p=0.001, 1 dollar=1170.24 Korean Won (2020.1.25). Total cost for 1yr/person : Dementia 493.20286±158.21327(US dollar), Depression 66.83514±3.857845(Us dollar), p=0.001. Dementia 64 years below(US dollar) : Men 440.6060 , Women 203.0120, Dementia 65‐80>years(US dollar) : Men 441.9200, Women 639.2740, Depression 64years below(US dollar) : Men 69.0080, Women 63.0420, Depression 65‐80>years(US dollar) : Men 64.2980, Women 61.9620.

Conclusion

The results of the above study analyzed data on dementia and depression using big data from the Korea Health Insurance Review and Assessment Service, and proved that the number of cases of dementia was less than that of depression, but the treatment cost was higher. The cost of treatment of dementia was much higher for men before 64, but after 65, the cost burden for women increased.
TMEM97 is a potential amyloid beta receptor in human Alzheimer’s disease synapses
Authors: Colom‐Cadena Martí , Tulloch Jane , Rose Jamie , Smith Colin , Spires‐Jones Tara
Published: December 2020

Background

Synapse loss correlates strongly with cognitive decline in Alzheimer’s disease (AD), and abundant evidence from animal and cell models implicates soluble amyloid beta in synaptic dysfunction and loss. While many candidate synaptic receptors for amyloid beta have been observed in model systems, the physiologically relevant amyloid beta receptor(s) involved in synapse degeneration in human AD brain remain unknown. Here we tested the hypothesis that TMEM97, recently discovered to be the sigma 2 receptor, binds amyloid beta in synapses in human AD brain.

Methods

To do this, we combined high resolution array tomography with Forster resonance energy transfer (FRET) to examine whether amyloid beta and candidate receptors are in close enough proximity to be interacting in human postmortem brain samples. We examined temporal cortex from AD (n = 9) and age matched control (n = 6) cases. Ribbons of 70 nm serial sections from human brain samples were stained with antibodies to label pre synapses, post‐synapses, amyloid beta, and TMEM97, and images before and after acceptor photobleaching were obtained on a confocal microscope.

Results

We observe that TMEM97 is present in a higher proportion of post‐synapses in AD brain compared to control brain and that in AD a higher proportion of post‐synapses contain both TMEM97 and amyloid beta. Further, TMEM97 and amyloid beta are in close enough proximity to generate a FRET signal in post‐synaptic densities. Cellular prion protein was also in close proximity to amyloid beta, but as expected, pre synaptic and post‐synaptic markers were too far apart to generate a FRET signal (negative control).

Conclusions

These data support a role for TMEM97 as a synaptic receptor for amyloid beta in human Alzheimer’s disease brain where it may mediate synaptotoxicity.
Single‐cell profiling of circulating and brain‐resident immune cells in a mouse model for amyloidosis and in aged mice
Authors: van Olst Lynn , Verhoeff Jan , Schetters Sjoerd T.T. , Hulshof Lianne A. , van Dijk Roland , van der Pol Susanne M.A. , Schouten Marijn , Vallejo Juan J. Garcia , van Der Flier Wiesje , Teunissen Charlotte E. , Middeldorp Jinte , de Vries Helga E.
Published: December 2020

Background

Emerging evidence suggests that peripheral immunity plays an important role in the progression of Alzheimer’s disease (AD) (Gate et al., 2020). However, more understanding on how peripheral immune cells respond to AD pathology is needed before utilizing the immune system further for early diagnosis and therapeutic treatment. Here, we aimed to map the immune system in the early stages of amyloidosis. In addition, we aimed to characterize the aged immune system and to study the effect of age‐related circulating immune factors on the immune response.

Method

We used 6‐month‐old APPswe/PS1dE9 (APP/PS1) transgenic and wild type (WT) mice to study the immune response to amyloid‐beta pathology and 20 month‐old WT mice for characterization of the aged immune system. In addition, both 6‐month‐old WT and APP/PS1 mice received multiple injections with aged blood plasma derived from 20‐month‐old WT mice. Next, immunohistochemical and high‐dimensional single‐cell analysis using time‐of‐flight mass cytometry (CyTOF), allowing detection of different immune populations and their activation status, was performed to map the circulating and brain‐resident immune cells in the different conditions (Figure 1).

Result

Immunohistochemical analysis revealed that T cell infiltration in the 6‐month‐old APP/PS1 brain coincided with early amyloid‐beta plaque formation. Single cell analysis of circulating and brain‐resident immune cells of APP/PS1 mice showed that especially T cells clustered in different cell‐subsets and had increased expression of activation and cell‐adhesion molecules compared to young WT mice. In contrast, circulating and brain‐resident T cells of aged mice contained more regulatory cell subsets and increasingly expressed molecules involved in immune inhibition. Interestingly, initial analysis revealed that injections with aged WT blood plasma partially reduced the aforementioned differences in T cells between young WT and APP/PS1 mice.

Conclusion

We found that circulating and brain‐resident T cells were different in their subsets and expression profile in early amyloid‐beta accumulation and in aging. In addition, the activation status of APP/PS1‐derived T cells was reduced after exposure to aged WT blood plasma resulting in a T‐cell signature more similar to young WT mice. Currently, we are further investigating the peripheral immune response to amyloid‐beta pathology by lipid‐ and RNA profiling of the circulating immune cells.
Machine learning regression analysis predicts brain amyloid‐β burden: A multimodal neuroimaging research study
Authors: Lin Li , Wang Xiaoni , Wang Xiaoqi , Li Xuanyu , Sun Yu , Du Wenying , Chen Guanqun , Han Ying
Published: December 2020

Background

Recent criteria have unveiled the importance of biomarkers in the continuum of Alzheimer's disease, which greatly enhances the progression of clinical trials of prevention and treatment. However, the expanding cost and resources limit the first‐line brain amyloid measurement techniques.

Objective

We aimed to develop an inexpensive and sensitive method to predict brain amyloid‐β burden by integrating machine learning and multimodal MRI.

Methods

Eighty‐three elders were enrolled from the Xuanwu Hospital. Brain amyloid‐β burden, structural and functional changes were respectively assessed with (18)F‐AV45 amyloid PET, structural and diffusion MRI, functional MRI. Using regression machine implementations, we predicted brain amyloid‐β level by voxel‐based morphometry, fractional anisotropy and fractional amplitude of low frequency fluctuations (fALFF).

Results

We found that extracted features could predict brain amyloid‐β burden, using voxel‐based morphometry (r=0.55, p=0.001) or/and fractional anisotropy (r=0.36, p=0.002), but not fALFF(r=0.07, p=0.2388). These results were replicated using cross‐validation procedures and these models were statistical significance determined by permutation testing. The brain regions that showed most important to predict amyloid‐β burden were superior temporal gyrus, parahippocampal gyrus, inferior frontal gyrus and hippocampus.

Conclusion

The current study showed high correlation between the structural and diffusion MRI indexes and amyloid burden in the elders which opens a new possibility for early diagnosis of AD.
Trajectory of apathy, cognition and neural correlates in the decades before symptoms in frontotemporal dementia
Authors: Malpetti Maura , Kievit Rogier A , Jones P Simon , Rittman Timothy , Tsvetanov Kamen A , van Swieten John C , Borroni Barbara , Galimberti Daniela , Sanchez‐Valle Raquel , Laforce Robert , Moreno Fermin , Synofzik Matthis , Graff Caroline , Masellis Mario , Tartaglia Carmela , Vandenberghe Rik , Finger Elizabeth , Tagliavini Fabrizio , de Mendonca Alexandre , Santana Isabel , Butler Christopher , Ducharme Simon , Gerhard Alexander , Danek Adrian , Levin Johannes , Otto Markus , Frisoni Giovanni B , Ghidoni Roberta , Heller Carolin , Todd Emily , Bocchetta Martina , Convery Rhian S , Peakman Georgia , Moore Katrina M , Rohrer Jonathan D , Rowe James B
Published: December 2020

Background

In frontotemporal dementia (FTD), apathy is reported to negatively impact the prognosis and survival of patients. The study of genetic FTD in its pre‐symptomatic period permits the investigation of markers in the early stages of disease progression. Therefore, in pre‐symptomatic gene carriers in the multicentre Genetic FTD Initiative (GENFI), we examined longitudinal apathy changes in association with cognitive decline over time, and baseline measures of atrophy.

Method

Six hundred participants from Data Freeze 4 (2019) were included: 304 pre‐symptomatic mutation carriers, and 296 family members without mutations. Clinical assessment and a structural MRI scan were undertaken at baseline, and annually for at least 2‐years. Latent Growth Curve modelling (LGCM) was used to assess: 1) longitudinal changes in apathy, as measured by the apathy subscale of the Revised Cambridge Behavioural Inventory; 2) the relationship with longitudinal changes in executive function; 3) the association with baseline regional grey matter volumes. The time to the expected year of symptom onset was included as a covariate.

Result

Univariate LGCM identified a significant linear increase in apathy scores for pre‐symptomatic carriers (estimate= 0.51, se=0.18, z scores= 2.88, p=0.004), but not in non‐carriers (estimate= 0.08, se=0.08, z scores=1.04, p=0.30). An equality constrained comparison suggested a significant group difference in the progression of apathy (i.e. the slope) ((∆ χ2=10.14; p=0.0015). Pre‐symptomatic carriers also had a significant decline in executive functions (est=‐0.07, se=0.03, z scores=‐2.49, p=0.017), which was predicted by baseline apathy (standard estimate=‐0.40, p=0.008). In pre‐symptomatic carriers only, the annual rate of change in apathy was significantly associated with brain volume in frontal lobe (standard estimate=‐0.47, p=0.008) and cingulate cortex (standard estimate=‐0.29, p=0.05) at the baseline.

Conclusion

Apathy progresses significantly in pre‐symptomatic FTD and predicts a sub‐clinical deterioration of executive performance in gene carriers. Apathy changes over 2 years are associated with volume in the frontal lobe and cingulate gyrus measured at the baseline. We suggest that apathy may be a modifiable factor to protect function and cognition in those with, or at risk of, frontotemporal dementia.
Association of trajectories of depressive symptoms with vascular risk factors, cognitive function and adverse brain outcomes: A 28‐year follow‐up
Authors: Demnitz Naiara , Anatürk Melis , Allan Charlotte L , Filippini Nicola , Griffanti Ludovica , Mackay Clare , Mahmood Abda , Sexton Claire E , Suri Sana , Topiwala Anya G , Zsoldos Enikő , Kivimaki Mika , Singh‐Manoux Archana , Ebmeier Klaus P
Published: December 2020

Background

Depressive symptoms are related to an increased risk of cognitive decline. Trajectories of depressive symptoms over the lifespan vary between people, but it is unclear whether these differences may exhibit dissociable structural changes in brain white matter and cognitive changes, including reduced executive function.

Method

In order to compare microvascular and cognitive characteristics of groups with different trajectories of depressive symptoms, we examined 774 participants of the Whitehall II MRI Sub‐study, who had completed the depressive subscale of the General Health Questionnaire at baseline in 1985‐88 and then on average 3, 5, 11, 14, 17, 19, 22, and 25 years later. At 27.3 years after the first examination, participants underwent a multimodal MRI examinations to characterise white matter hyperintensities and white matter microstructure, and completed a detailed neuropsychological test battery to assess cognition. Final examination was 28.8 years after the first examination, including MMSE cognitive screening test.

Result

Using K‐means cluster modelling, we identified five trajectory groups of depressive symptoms: consistent low scorers (n = 505), improvers with highest depression scores at the beginning of the follow‐up period (n = 123), intermediate scorers (n = 89) with a peak in caseness in the middle of the follow‐up period, a subgroup deteriorating towards the time of the scan (n = 29), and consistent high scorers (n = 28). The ‘deteriorators’, but not the consistently high scorers, showed higher mean white matter diffusivity, larger volumes of white matter hyperintensities and impaired executive function. In addition, ‘deteriorators’ had higher Framingham Stroke Risk scores and raised mean arterial blood pressure than consistently high scorers, indicating a higher load of vascular risk factors.

Conclusion

A ‘deteriorating’ trajectory pattern in depressive symptoms was associated with increased vascular risk factors, indices of reduced white matter microstructure and reduced executive function. Altogether, our findings suggest that tracking depressive symptoms over time may be a useful tool to identify pre‐clinical phenotypes in the community that are at risk of later cognitive decline.
The quantitative analysis of tau deposition using [F18] PI‐2620 dynamic PET acquisition in cognitively normal subjects, mild cognitive impairment and Alzheimer’s disease patients
Authors: Jantarato Attapon , Vachatimanont Sira , Assanasen Jintana , Kunawudhi Anchisa , Promteangtrong Chetsadaporn , Chotipanich Chanisa
Published: December 2020

Background

F‐18 PI 2620 has been reported as an effective tau binding radiotracer. However, there are few reports focusing on the quantitative analysis. Hence, this study aims on the quantitative analysis of PI 2620 in individuals with normal cognition, MCI and AD.

Method

Twenty‐six cognitively normal (CN; 8 men, 18 women; aged 56–71 years; mean age ± SD: 63.81 ± 4.6 years), 7 Alzheimer’s disease (AD; 3 men, 4 women; aged 59–74 years; mean age ± SD 64.57 ± 6.09 years), and 36 mild cognitive impairment (MCI; 11 men, 25 women; aged 56–85 years; mean age ± SD 66.61 ± 5.92 years) individuals were enrolled. A dynamic F‐18 PI 2620 PET was performed at 30‐75 minutes post‐injection. Co‐registration was employed between the PET and T1‐weighted MRI. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P‐mod software with the Automated Anatomical Labeling (AAL)‐merged atlas was applied to create volumes of interest. Pair t‐test in STATA was applied for statistical analysis.

Result

In AD group, occipital lobe had the most significantly higher mean SUVR (1.46±0.57) compared to both CN (1.08±0.09, p<0.01) and MCI group (1.06±0.08, p<0.001). Comparing to CN, AD brain also showed significantly higher mean SUVR (p<0.05) in fusiform gyrus (1.06±0.09 vs. 1.49±0.86), inferior temporal (1.07±0.07 vs. 1.46±0.08), parietal lobe (1.01±0.13 vs. 1.27±1.45), lingual gyrus(1.08±0.11 vs. 1.29±0.41) and precuneus (1.02±0.12 vs. 1.27±0.45).Likewise the AD group demonstrated higher mean SUVR than MCI in precuneus (1.00+0.07), lingual (1.07±0.12), inferior temporal (1.06±0.10), fusiform (1.08±0.11), supramarginal (0.97±0.07), orbitofrontal (0.97±0.07) and superior temporal (0.95±0.07) regions. The remaining observed regions including striatum, basal ganglia, thalamus, white matter, showed low SUVR across three groups without statistical significant.

Conclusion

The significantly higher mean SUVR of F‐18 PI 2620 was observed in the AD group at significant brain area for diagnosis Alzheimer’s disease demonstrated tau protein deposit in‐concordance with the Braak Staging III‐V, providing useful information to differentiate AD from CN and MCI. Moreover, low SUVR in deep striatum and thalamus could be useful for the exclusion of primary tauopathies such as progressive supranuclear palsy.
Self‐reported quality of sleep is related to frontoparietal network connectivity in mild cognitive impairment
Authors: Pini Lorenzo , Wennberg Alexandra MV , Mitolo Micaela , Meneghello Francesca , Burgio Francesca , Semenza Carlo , Venneri Annalena , Mantini Dante , Vallesi Antonino
Published: December 2020

Background

Sleep has been identified as a modifiable factor involved in both the development and progression of Alzheimer’s disease (AD). Previous findings have suggested that poor sleep may be associated with increased risk of AD. Conversely, higher quality of sleep may slow progression of pathophysiological mechanisms in mild cognitive impairment (MCI) through functional connectivity reorganization of neural networks underlying higher cognitive functions.

Method

In clinic, 38 MCI patients and 38 age‐matched controls completed structural magnetic resonance imaging (MRI), resting‐state functional MRI (rs‐fMRI), and a cognitive test battery, covering memory, executive functions, and language. The Sleep Continuity in Alzheimer’s Disease Scale (SCADS) was used to assess sleep quality. Patients were stratified into “good” (n=20) and “poor” (n=18) sleepers, using the median SCADS score as a cut‐point. Default mode (DMN) and left and right frontoparietal (FPN) networks were reconstructed through an independent component analysis approach. Differences in network connectivity across MCI groups were investigated with non‐parametric inference using FSL randomize (n=5000 permutations), corrected at a threshold‐free‐cluster enhancement level of pFWE < 0.025. Grey matter and sex were inserted as covariates in the analysis. The same model was implemented to investigate associations between connectivity and cognition in MCI. Finally, between‐network connectivity was assessed through partial correlation with sex as covariate.

Result

MCI good sleepers showed increased FPN connectivity compared to MCI poor sleepers. Increased FPN connectivity was positively associated with language performance in the former group. Finally, we found a positive coupling connectivity between DMN and FPN and between left and right FPN in MCI good sleepers, while this pattern was disrupted in MCI patients with lower quality of sleep.

Conclusion

These findings suggest a relationship between sleep quality and FPN connectivity in MCI, highlighting possible sleep‐induced compensatory mechanisms. Future studies in larger samples using longitudinal methods and objective measures of sleep will be necessary to confirm this finding. However, these results further support the concept that better sleep may be protective on the pathway to AD.
Tauopathies: Need for education and advocacy — Que Tau? A pilot study
Authors: Komatsu Ricardo S. , Komatsu Caroline
Published: December 2020

Introduction

When we ask a medical student or a medical resident about tauopathies our perception of the level of knowledge is in average low. It reinforces the need for education and advocacy of tauopathies involving health care professionals and general population in our country, and probably worldwide.

Objective

To disseminate information about tauopathies using social media campaign.

Methods

We planned an educational program for medical students and medical residents named Que Tau? (in Portuguese Que Tal, means: What about?). We will use social media, sending information by messaging app (WhatsApp and/or Telegram) using images (jpg), short videos, texts or articles (PDF). A pilot study will involve a sample of 60 undergraduate and 60 postgraduate students of a medical school in Brazil, and the same number of controls. Both groups will be asked about tauopathies key concepts three months later the messages.

Results

This strategy to use smartphones to disseminate information about tauopathies can result in a good initiative to take attention of medical residents and medical students for tauopathies and to stimulate future actions to fight these diseases.

Conclusion

We expect that he level of knowledge about tauopathies can increase between medical students and residents according to dissemination of information using social media campaign.
Dementia with Lewy bodies: Characteristics of the prodromal stage in a nationwide longitudinal cohort
Authors: Blanc Frédéric , Bouteloup Vincent , Paquet Claire , Chupin Marie , Pasquier Florence , Gabelle Audrey , Ceccaldi Mathieu , Sousa Paulo Loureiro , Salmon Pierre Krolak , David Renaud , Fischer Clara , Dartigues Jean‐François , Wallon David , Sauvée Mathilde , Moreaud Olivier , Belin Catherine , Botzung Anne , Albasser Timothee , Demuynck Catherine , Namer Izzie , Habert Marie‐Odile , Kremer Stephane , Bousiges Olivier , Martin‐Hunyadi Catherine , Philippi Nathalie , Chêne Geneviève , Cretin Benjamin , Mangin Jean‐Francois , Dufouil Carole
Published: December 2020

Background

Little is known about the prodromal phase of Dementia with Lewy bodies (DLB). In a large prospective cohort of patients attending memory clinics presenting either subjective cognitive impairment (SCI) and mild neurocognitive impairment (MCI) patients, we undertook an ancillary study aiming at detecting early DLB in a longitudinal framework.

Method

We conducted a french nationwide prospective cohort of patients with cognitive complaints and a minimum follow‐up of 4 years. Participants in the Memento cohort study were recruited for either isolated subjective cognitive impairment (SCI) or mild neurocognitive impairment (MCI). Among them, patients from 12 memory resource and research centers, representing eight hundred ninety‐two patients were included in the Lewy sub‐study. Probable Pro‐DLB diagnosis was done using a two‐criteria cut‐off score among the four core clinical features of Dementia with Lewy bodies. This Pro‐DLB group was compared to two other groups: one without any core symptoms (NS group), and the one with one core symptom (1S group). A comprehensive cognitive battery, brain 3D volumetric MRI, CSF, FDG PET and amyloid PET were done.

Result

The pro‐DLB group comprised 148 patients (16.6%). Compared to the other two groups, the neuropsychological profile of the pro‐DLB group showed, regarding cognition, more multidomain (59.8%) MCI with slower processing speed, semantic and neurovisual impairment, and regarding behavior, a higher proportion of patients with depression, anxiety, and apathy. Pro‐DLB patients also presented more autonomic symptoms, including lower libido, constipation, rhinorrhea, sicca syndrome, and photophobia. The Pro‐DLB group had isolated lower P‐Tau and no difference in terms of amyloid PET and FDG PET. Brain MRI analysis showed widening of sulci including fronto‐insular, occipital and olfactory sulci (FDR corrected). Evolution to dementia was not different between the three groups after 4 years of follow‐up.

Conclusion

Patients with pro‐DLB represented 16.6% of SCI and MCI patients, a finding consistent with the proportion observed at the stage of dementia. In addition to the core symptoms, pro‐DLB patients presented cognitive, behavioral and autonomic symptoms. Biomarkers confirmed the non‐Alzheimer profile. The occipital, fronto‐insular, and olfactory bulb involvement on brain MRI was consistent with the symptoms and known neuropathology.
Tau PET imaging, MRI and cognitive progression in subjects with progressive amnesia and suspected non‐Alzheimer pathophysiology (SNAP)
Authors: Lagarde Julien , Olivieri Pauline , Hamelin Lorraine , Valabrègue Romain , Caillé Fabien , Gervais Philippe , Bottlaender Michel , Sarazin Marie
Published: December 2020

Background

While progressive amnesia of the hippocampal type is most often due to Alzheimer’s disease (AD) pathology, other etiologies are not rare during aging, including limbic‐predominant age‐related TDP‐43 encephalopathy (LATE) with or without Hippocampal Sclerosis (HS) and Primary age‐related tauopathy (PART). These pathological conditions differ from AD by the lack of cortical amyloid deposition, but the amnestic syndrome mimicking AD can lead to mis‐diagnosis. By coupling amyloid and tau PET imaging in patients with progressive amnesia, we investigated, in vivo, clinical and biological markers that differentiate suspected non‐AD pathophysiology (SNAP) from AD patients.

Method

We included 41 patients with a progressive episodic memory deficit of the hippocampal type (CDR≤ 1), and 30 controls. All patients underwent both PiB‐PET and AV‐1451‐PET. According to their amyloid PET status, we classified patients in SNAP (negative PiB‐PET defined by a GCI<1.45, n=10) and prodromal‐AD (positive PiB‐PET, n=31). Tau‐PET were analyzed individually vs the control group by using Z‐scores in each ROI. Participants were followed up annually for 2 years

Result

SNAP patients were older than AD (77.9+/‐5 vs 70.0+/‐6.8 years) and the proportion of APOE4 carriers was lower (28% vs 62%). No difference in baseline neuropsychological scores was found between SNAP and AD patients regarding MMSE (22.9+/‐2.6 vs 24.2+/‐3.0), verbal or visual episodic memory, or anxiety/depression scales. Volumes of the hippocampus and entorhinal cortex were lower in SNAP and prodromal‐AD than in controls, without any significant difference between both patient groups. As expected, CSF Ab42/Tau and Ab42/Phospho‐tau ratios were lower in SNAP compared to prodromal AD. Tau‐PET imaging was negative in all SNAP patients except one (fronto‐temporal binding), while tau deposition was observed in all AD patients in the temporal +/‐ parietal cortex. Clinical follow‐up at one and two years showed mild dysexecutive syndrome in SNAP and mild parietal cognitive dysfunction in prodromal‐AD.

Conclusion

Amnesia of the hippocampal type not due to AD was observed in 24% of our cohort, with similar severity of amnesia and hippocampal/entorhinal atrophy as in prodromal‐AD, but possibly distinct longitudinal clinical trajectories. Molecular PET imaging suggested a non‐tau pathology in 9 patients and a possible non‐AD tauopathy in one.
An in‐depth analysis of a large national survey on person‐specific outcome measures (EPSOMS)
Authors: Sheehan Shane , Luz Saturnino , Saunders Stina , Evans Alison , Ritchie Craig W. , Terrera Graciela Muniz
Published: December 2020

Background

The ePSOM programme, a collaboration between the University of Edinburgh and Alzheimer’s Research UK,was prompted by the recognition that outcome measures currently used in clinical trials in prodromal and preclinical neurodegenerative diseases do not capture the research participants’ views of effectiveness. This 4‐stage programme involved an evidence review and programme methodology, focus groups to identify key domains of importance to people at various degrees of neurodegenerative disease, a National online survey and the development of an App development which will permit the design of an outcome measure for use in regulatory trials. Here we present results from an in‐depth analyses of the national survey responded by over 5,500 individuals.

Method

A short online survey collected information about individuals sociodemographic background and bran health and on 5 domains identified as relevant to individuals based on results from focus groups of people living with memory problems, healthy volunteers and telephone interviews with health and social care professionals. These domains covered everyday functioning, enjoyable activities, relationships and social interactions, cognitive function and identity. Data was analysed using clustering and natural language programming techniques.

Result

The survey was completed by 5,807 individuals, of which 75% were women. Average age of respondents was 58.6 (SD=13.8), living in urban areas (61%) and married (63.4%). There are 82514 responses across the five domains. The largest cluster of responses are associated with “Reading” this cluster accounts for 3107 of the answers given. Closely followed by “Car/Drive” with 2969 answers. Other clusters identified with above 1000 answers are “Walk”, “Garden”, “Cook”, “Understand”, “Chat”, “Remember” and “Shop”.

Conclusion

Our work generated strong and new evidence based on a large sample of individuals. Results are relevant for the future development of patient reported outcomes.
Exploring opportunities for the integration of traditional healing medicine in the care and prevention of dementia for first nations people from the Wiikwemikoong Unceded Territory on Manitoulin Island in Northern Ontario, Canada
Authors: Shrestha Hom Lal , Pitawanakwat Karen , Wabie Joey‐Lynn , Maar Marion , Walker Jennifer D
Published: December 2020

Background

Traditional healing methods that prioritize the worldviews and knowledge of First Nations people and communities are pivotal and can be integrated throughout the care process in the way that dementia is screened for and diagnosed. The Canadian Indigenous Cognitive Assessment Tool is a culturally safe dementia a screening tool that requires ongoing thoughtful integration of traditional healing medicine practices to be successfully integrated into current health policy and practice across Canada. In Canada, over the next decade, the number of First Nations people over the age of 60 with dementia will increase four‐fold. This is in comparison to a 2.3‐fold increase in the non‐First Nations population. First Nations Elders seek spiritual, emotional, physical, and mental balance in preventing dementia and empowering First Nations people to live healthy lives through traditional healing medicine practices. Access to culturally safe geriatric care and dementia diagnosis among First Nations older adults is a challenge and there is little research aimed at addressing this gap. Within this limited area of research, there is even less research dedicated to how First Nations older adults’ access to traditional medicines, healing, and practices in the prevention and maintenance of dementia care. Within this forum, this presentation will highlight my learning and my passion for this research area. Through a decolonizing research approach, I propose exploring the pathways that will help to fill the gap between traditional healers and health care providers within dementia care and prevention. The primary research question is rooted in First Nations community priorities and asks: “what are the pathways to fill the gap between care providers and traditional healers to integrate traditionally healing medicine practices into dementia care and prevention in Wiikwemkoong Unceded Territory on Manitoulin Island?” Through relationship‐building and close collaboration with the First Nations community members from the Wiikwemikoong Unceded Territory, this work will exemplify how to frame and uncover the missing link between First Nations use of traditional healing medicines and First Nations dementia care within a mainstream medical system by carrying out an exploratory qualitative Indigenous research design and method.
Cognitive impairment among community‐dwelling, off‐reserve indigenous populations in Canada
Authors: Warren Laura A , Walker Jennifer D , Martiniuk Alexandra , Rosella Laura
Published: December 2020

Background

Limited research suggests the prevalence of cognitive impairment among Indigenous populations in Canada may be higher than that among non‐Indigenous populations. This project is focused on the understudied off‐reserve Indigenous population. We used the social determinants of health model and two‐eyed seeing approach to characterize the epidemiology of cognitive impairment in Canada’s community‐dwelling, off‐reserve Indigenous population in comparison to the non‐Indigenous population using data from the Canadian Community Health Survey (CCHS).

Method

A Community Advisory Board was established to provide leadership, support and direction to the research. Weights were applied to generalize estimates from the sampling population to the general population. Chi‐square tests were used to compare frequencies and prevalence estimates. Risk factors for cognitive impairment will be identified using PROC GENMOD to build a multivariate logistic regression model for Indigenous and non‐Indigenous participants.

Result

Weighted estimates are presented for preliminary results. The prevalence of risk factors for cognitive impairment were generally higher for the Indigenous population (e.g. smoking status, level of education, food security, marital status, rural residency, heart disease, falls, diabetes, emotional health) in comparison to the non‐Indigenous population (Tables 1 & 2; p<0.01). The Indigenous population was younger than the non‐Indigenous population with nearly half of the Indigenous population being 45‐54 years of age (49% vs 38%, p<0.01). Despite the younger age profile of the Indigenous population, the overall prevalence of mild (29% vs 25%) and severe cognitive impairment (4% vs 2%) were higher for the Indigenous population compared to the non‐Indigenous population (Table 2; p<0.01). The prevalence of dementia was <1% for both study populations (p=0.33). Given the low prevalence of dementia, our bivariate and multivariable models will focus on cognitive impairment. Age‐specific cognitive impairment prevalence estimates will be reported for each age group. Odds ratios will be reported from the final multivariable model for Indigenous and non‐Indigenous participants.

Conclusion

This is the first study focused on cognitive impairment among the community‐dwelling, off‐reserve Indigenous population in Canada. By characterizing the epidemiology of cognitive impairment in Indigenous populations we will increase awareness of cognitive impairment and associated risk factors in off‐reserve Indigenous populations.
Protective and risk factors of cognitive decline and dementia with a special emphasis on social health: A systematic mapping review
Authors: Lenart Marta , Luc Mateusz , Pawlowski Marcin , Seifert Imke , Wiegelmann Henrik , Szczesniak Dorota , Gerhardus Ansgar , Wolf‐Ostermann Karin , Rouwette Etienne , Rymaszewska Joanna
Published: December 2020

Background

Insufficient knowledge about dementia and factors influencing its course account for the scarcity of effective interventions and thereby, spiralling social costs related to care for an increasing population of people with dementia. This systematic mapping review is a part of JPND project Social Health And Reserve in the Dementia patient journey (SHARED), aimed to comprehensively map existing evidence on factors impacting cognitive functions and the development and course of dementia, along with a special emphasis on the social health.

Method

This review followed PRISMA Checklist. Medline, PsycINFO, CINAHL Complete, Cochrane Database and Epistemonikos were searched for systematic reviews and meta‐analyses from 2009 to 2019. Reviewers independently screened, reviewed and assessed methodological quality of articles.

Result

Among the 314 included studies, factors affecting cognitive functions and the development of dementia were recorded 586 times under 7 categories: personal (22), socioeconomic (33), lifestyle (143), psychological (53), environmental (25), neurobiological (278) and social health (32). Among these records, risk factors were the most frequently reported (350 times), while protective factors were mainly detected in the lifestyle (58) and social health (15) categories. In addition, the type of impact was unclear for 84 reported mentions.

Conclusion

The results indicate the dominance of research on neurobiological (47.4%) over social health (5.5%) evidence, as well as on risk (59.7%) over protective (14.8%) factors. Obtained data show the potential of studies on social health in the context of dementia prevention and the need for further research on lesser known factors positively influencing cognitive functions.
Challenges in the development of accurate normative neuropsychological test data for older adults: Findings from the HELIAD Study
Authors: Arampatzi Xanthi , Margioti Eleni , Yannakoulia Mary , Hadjigeorgiou Georgios M. , Dardiotis Efthimios , Sakka Paraskevi , Scarmeas Nikolaos , Kosmidis Mary
Published: December 2020

Background

Normative data collected from older adult cohorts may be tainted by the inadvertent inclusion of undiagnosed individuals at the very early stage of a dementia process or Mild Cognitive Impairment (MCI). To avoid this pitfall, we developed normative data from an older adult group who remained cognitively intact at follow‐up examination. The present work addresses the challenge and the absence of appropriate normative data for a range of neuropsychological tests in older adults in Greece.

Method

1031 community dwelling participants (age≥65) underwent neurological and neuropsychological assessment on two occasions with a mean interval of 2.8 years (range:1.2‐5.2; SD:0.8) for the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). A value of 0 or 0.5 for the Clinical Dementia Rating (CDR) and a threshold value of ≥ 26 on the Mini Mental State Examination (MMSE) were used as clinical diagnostic criteria to determine the cognitive status of the participants. Based on these criteria, 750 individuals were cognitively intact in both evaluations and their data were used for norms development. Participants received a comprehensive neuropsychological assessment encompassing five cognitive domains: memory, language, attention/speed, executive and visual‐spatial functioning. Multiple linear regression models were performed, with age at baseline (years), education (years) and sex as the demographic predictors for regression‐based normative formulae, and raw test scores as the dependent variables. The effects of age, education and sex were investigated for each test and subtest separately. Discrete norms were also derived, stratified by four age strata (64‐69, 70‐74, 75‐79, 80‐89) and by three education strata (0, 1‐9, 10+).

Result

Regression analyses revealed that education was associated with all test scores, whereas age was an important predictor of all but a few visuoperceptual, executive functioning and memory variables. Women outperformed men on verbal memory, attention/information processing speed and subtests of executive functioning. Men, however, outperformed women on visual memory recall and visuospatial perception.

Conclusion

The current study provides sound normative data for widely‐used neuropsychological tests among older adults, untainted by potential early and undiagnosed cognitive impairment. We report both discrete and regression‐based norms for use in clinical settings to identify cognitive decline in older adults.
Neuroanatomical signature of super‐ageing: Structural brain study of youthful episodic memory in people over the age of 80
Authors: Pascual Marta Garo , Zhang Linda , Defelipe Javier , Gaser Christian , Medina Miguel , Strange Bryan A
Published: December 2020

Background

Superagers are people over the age of 80 that possess an episodic memory function of a person 20‐30 years younger. By drawing on a large (N=1213) longitudinal cohort of elderly individuals, we aimed to identify a superager subgroup and to determine key differences, including brain structure, between superagers and peers with normal episodic memory for their age.

Method

A sample of 64 superagers (mean age 81.9 years, 59.4% women) and 19 age‐matched controls (mean age 82.6 years, 57.9% women) from the Vallecas Project cohort based at Fundación CIEN were selected according to their episodic memory score in the Free and Cued Selective Reminding Test; superagers scored at or above the mean value of a 50‐56yo person and controls scored within one standard deviation for their age. Demographic, genetic (APOE), lifestyle, clinical and neuropsychological variables were compared. Structural whole‐brain measures of grey matter volume are analised across groups at baseline and over time for up to 5 years (2‐6 time points) using CAT12 toolbox in SPM12.

Result

There were no differences in age, sex, years of education, current frequency of physical exercise or APOE genotype across groups. A history of anxiety, depression and cardiopathy was less frequent in superagers. At baseline, a higher grey matter volume in superagers compared to controls was shown in the bilateral anterior thalamus and regions within the temporal lobe including bilateral effects in the hippocampus, the amygdala, the entorhinal cortex, the parahippocampal gyrus and the fusiform gyrus (p < 0.05 FWE corrected). The longitudinal analysis revealed reduced grey matter volume loss over time in superagers in bilateral hippocampus, entorhinal cortex, parahippocampal gyrus, the left amygdala, bilateral basal forebrain, caudate, anterior insula, and right posterior cingulate (p < 0.05 FWE corrected).

Conclusion

Baseline differences between these two populations were located in a neuroanatomical network linked with memory function including key areas within the temporal lobe and also the anterior thalamus. The atrophy rate over time in these temporal regions is slower for the superager group, suggesting that they are more resistant than controls to the ageing decline of memory‐related areas.
Race or ethnicity is a factor that should be considered for establishing the normative data of subcortical brain volumes in normal aging
Authors: Choi Yu Yong , Kim Hoowon , Lee Kun Ho
Published: December 2020

Background

The norms of aging brain are important to diagnose degenerative brain diseases. However existing analyses have mainly focused on Caucasian samples. Particularly, the aging brain of East Asians has not been fully studied. The study aimed to investigate ethnic differences in aging process of regional brain volumes, specifically to determine to what extent ethnicity affects the normative volumes of subcortical brain structures in normal elderly people.

Method

We measured subcortical volumes from brain magnetic resonance (MR) images of 1,686 cognitively normal elderly Koreans aged 59 to 89 using FreeSurfer. For Caucasians, the brain images of 855 Caucasian‐Non‐Hispanic subjects were selected from the ADNI and OASIS datasets. The regression model predicting brain volumes were built using ethnicity, age, sex, intracranial volume (ICV), magnetic field strength (MFS), and scanner manufacturers as predictors. Based on the prediction model, the z‐scores of each individual were calculated. To validate the z‐score for diagnosis, 420 Alzheimer’s disease (AD) subjects of Koreans and Caucasians, and the same number of normal subjects were selected. The four validation groups divided by race and diagnosis were age‐ and sex‐matched using a propensity score matching method.

Result

The models predicting subcortical volumes had a considerate amount of explained variance (mean R2: 31.8%, range: 12.7%–45.5%). Ethnicity explained substantial variances for thalamus, accumbens, and hippocampus (for all subcortical volumes, mean R2: 3.5%, range: 0.1%–11.6%), comparable to age (mean R2: 4.0%, range: 0.0%–12.2%).

Conclusion

Race or ethnicity should be considered for establishing the normative data of subcortical brain volumes in normal aging. Otherwise, it can mislead clinicians into making an incorrect diagnosis.
Loneliness and isolation among people with dementia and their carers: Prevalence, risk factors and a dyadic analysis
Authors: Rippon Isla , Victor Christina R , Quinn Catherine , Martyr Anthony , Matthews Fiona E , Clare Linda
Published: December 2020

Background

People with dementia and their carers may be vulnerable to loneliness and isolation. We investigated: (a) prevalence of, and risk factors for, loneliness and isolation among people with dementia and their carers and (b) the interrelationship between loneliness and isolation for dyads (person with dementia and carer).

Method

The IDEAL cohort of people with dementia and their carers includes two loneliness measures: the 6 item de Jong Gierveld (DJG) scale (range 0‐6 and classified: not lonely (0‐2), moderately lonely (3‐4) and severely lonely (5+)) and a single‐item question, plus a measure of social isolation, the six‐item Lubben social network scale (range 0‐30: not isolated (13+) or isolated (12 or less). For dyads consisting of a carer and a person with dementia, 1089 had complete data on loneliness and 1204 on social isolation. We report prevalence and examine loneliness/isolation risk factors using regression analysis for people with dementia and carers separately. We use Actor‐Partner Interdependence Models (APIM) to examine the relationship between isolation and loneliness within dyads and vice‐versa.

Result

Prevalence of severe loneliness for people with dementia was 10% (single item score) and 5% (DJG score 5+) (15% and 18% respectively for carers). One third of people with dementia, 35%, were at risk of isolation (18% of carers). Social isolation was the only risk factor for loneliness consistent for both carers and people with dementia. Risk factors for loneliness in carers were caregiving stress and relationship quality and in people with dementia living alone, depression and life satisfaction/quality of life. Loneliness ratings were congruent in 43.1% of dyads (67.8% for isolation). Dyadic analysis using APIM demonstrates that loneliness is affected by both individuals’ own isolation and that of their partners.There were also actor and partner effects for the association between loneliness and isolation.

Conclusion

Most people with dementia and their carers are neither lonely nor isolated. Risk factors for loneliness are different for carers and people with dementia. Isolation in the carers influences the loneliness of the person with dementia and vice versa.