bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and analytical characterization of novel tau Simoa assays targeting full‐length tau in CSF and mid‐tau in CSF and plasma
Authors: Vanbrabant Jeroen , Stoops Erik , Mauroo Kimberley , Bjerke Maria , Engelborghs Sebastiaan , Graham Danielle , Czerkowicz Julie , Rubel Carrie E.
Published: December 2021

Background

Biofluid markers of neurodegeneration and neural injury have great potential to elucidate disease mechanisms and accelerate development of experimental therapeutics. Cerebrospinal fluid (CSF) tau and phosphorylated tau are established biomarkers for AD, while plasma (N‐terminal) tau and phosphorylated tau (p‐tau) are being evaluated as complementary markers in a more accessible biofluid.

Tau is present in CSF and plasma in both full‐length and truncated forms, with great interest in characterizing and advancing these different forms as biomarkers to support clinical development. To contribute to the emerging research on tau fragments as biomarker, novel ultra‐sensitive immunoassays were developed targeting low‐abundant, non‐truncated full‐length (FL) tau in CSF and a mid‐region tau fragment in CSF and plasma.

Method

Simoa assays were developed using monoclonal antibodies (mAbs) targeting mid‐region tau epitopes or epitopes on full‐length tau.

Resulting assays were qualified and partially validated for analytical performance parameters: measuring range, specificity, repeatability, reproducibility and parallelism were assessed. Reagent and analyte stability were investigated by assessing hold time and freeze/thaw (F/T) stability. Paired clinical routine CSF and plasma samples were analysed (20 controls and 20 AD based upon CSF Aβ1‐42, t‐tau and p‐tau(T181) profile).

Result

FL‐ and mid‐tau Simoa assays were analytically characterized, upscaled to bulk volumes and partially validated. Both assays had acceptable repeatability and reproducibility (%CV <20%) for plasma and/or CSF. Parallelism was within acceptance criteria (ACC of 75‐125%; %CV <20%) for FL‐tau in 4 CSF samples and for mid‐tau in 4 CSF and 4 plasma samples. Analyte stability was demonstrated up to 5 F/T cycles and for a hold‐time of 24h at 21°C with a %CV<20%. Testing of clinical samples showed an increased CSF FL‐ (p<0.005) and mid‐Tau (p<0.0001) concentration in AD versus controls, whereas plasma mid‐tau did not increase.

Conclusion

A novel CSF assay for full length tau and a novel CSF/plasma assay for the mid‐tau fragment was developed, qualified and partially validated. The generated data indicated well‐performing tau assays available as RUO kits in pre‐clinical and clinical use in drug development programs.
Greater diffusion restriction in white matter tracts in preclinical AD
Authors: Benitez Andreana , Jensen Jens H. , Falangola Maria F. , Spampinato Maria Vittoria , Rieter William J. , Nietert Paul J. , Fountain‐Zaragoza Stephanie , Keith Kahtryn , Dhiman Siddhartha , Helpern Joseph A.
Published: December 2021

Background

The Alzheimer’s Continuum is biologically defined by beta‐amyloid deposition, encompassing individuals with or without other biomarker or clinical changes (Jack et al., 2018). Beta‐amyloid deposition is superimposed upon white matter degeneration in aging, but the degree to which these co‐occurring changes are characterized in vivo in the preclinical stage is less understood. The goal of this study was to use Diffusional Kurtosis Imaging (Jensen & Helpern, 2010) and biophysical modeling (Fieremans et al., 2011) to detect and describe amyloid‐related white matter changes in preclinical AD.

Method

141 cognitively unimpaired older adults ages 45 to 85 completed 3T brain MRI, amyloid PET (florbetapir, F18), and standard clinical and neuropsychological procedures (Besser et al., 2018). 51 had amyloid PET mSUVr values ≤ 1.21 and were designated as being on the Alzheimer’s Continuum (AB+); all other subjects were AB‐. DKI data were pre‐processed (Ades‐Aron et al., 2018), maps were computed using in‐house scripts (https://github.com/m‐ama/PyDesigner), and tensor‐based registration was performed using DTI‐TK (Zhang et al., 2007) as integrated with TBSS (Smith et al., 2006). Voxelwise and region of interest analyses of skeletonised maps were conducted to determine differences between AB+ and AB‐ groups, covarying for age, on conventional diffusivity (i.e. MD, FA) and biophysical modeling metrics that indicate extra‐axonal myelin/gliotic changes (i.e. D
e,⊥) and changes in axonal density (i.e. AWF).

Result

Voxelwise analysis indicated significantly greater diffusion restriction (i.e. lower MD, higher FA) in AB+ versus AB‐ subjects, with medium‐to‐large effect sizes (age‐adjusted |d|= 0.6 to 0.8). Region of interest analyses of the corpus callosum corroborated these findings, suggesting that these differences occur in late‐myelinating (genu) but not early‐myelinating (splenium) tracts (Fig. 1.B). This effect was likely driven by changes in the extra‐axonal space (i.e. lower D
e,⊥ in AB+).

Conclusion

The Alzheimer’s Continuum in preclinical AD is associated with greater diffusion restriction in white matter, preferentially in regions that myelinate later in life. Potential mechanisms include myelin breakdown and repair, oligodentritic activation, and inflammation (i.e. microgliosis, astrocytosis), suggesting non‐amyloid pathological changes upon which to focus disease monitoring or treatment development at the very earliest stages of disease.
Comparison of the prognostic value of cerebrospinal fluid and plasma neurofilament light in predicting longitudinal decline in white matter integrity among older adults
Authors: Moore Elizabeth E. , Shashikumar Niranjana , Pechman Kimberly R. , Bell Susan P. , Gifford Katherine A. , Landman Bennett A. , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L.
Published: December 2021

Background

Cerebrospinal fluid (CSF) neurofilament light (NFL) is a biomarker of neuroaxonal injury associated with cognitive decline, neurodegeneration, and white matter damage. Recent advances allow for plasma measurement of NFL, increasing accessibility of this biomarker. However, it is unknown if CSF and plasma NFL have similar prognostic value for predicting white matter damage. This study relates baseline CSF and plasma NFL concentrations to longitudinal change in white matter integrity in older adults.

Method

Vanderbilt Memory & Aging Project participants free of dementia at baseline (n=147, 72±6 years, 32% female) underwent baseline fasting lumbar puncture for CSF sampling and venous blood draw for plasma sampling. Participants completed serial 3T diffusion tensor imaging to assess white matter microstructural integrity at baseline, 18‐months, 3‐years, and 5‐years (follow‐up 4.3±1.3 years). Voxel‐wise linear mixed effects models with follow‐up time interaction terms related baseline CSF and plasma NFL separately to white matter microstructural trajectory, adjusting for baseline demographic and health variables, apolipoprotein E‐ε4 status, diagnosis, and follow‐up time. Follow‐up models tested interactions with diagnosis, amyloid‐β (Aβ), and phosphorylated tau (p‐tau).

Result

CSF and plasma NFL were correlated (r=0.50, p<0.001). In the entire sample, CSF NFL related to faster white matter microstructural integrity decline in frontal, parietal, occipital, and subcortical regions (corrected p‐values<0.05). Plasma NFL related to faster white matter microstructural integrity decline in frontal and subcortical regions (corrected p‐values<0.05). CSF (largest β=5.7x10‐9) and plasma (largest β=3.1x10‐7) associations were similar in strength. CSF NFL interacted with diagnosis and Aβ (corrected p‐values<0.04), with associations driven by MCI and Aβ negative participants. Plasma NFL interacted with Aβ and p‐tau (corrected p‐values<0.04), with associations driven by Aβ and p‐tau negative participants.

Conclusion

Among older adults, increased baseline CSF and plasma NFL concentrations predicted faster longitudinal decline in white matter integrity. While CSF NFL may relate to more widespread future white matter damage compared to plasma, plasma NFL could be an accessible biomarker for assessing future risk of white matter damage, particularly in individuals without Aβ or p‐tau pathology. CSF NFL may be a better prognostic biomarker in individuals with MCI, whereas plasma NFL has similar prognostic ability across diagnostic groups.
Menopause moderates sex differences in tau PET signal: Findings from the Framingham Study
Authors: Buckley Rachel F. , O’Donnell Adrienne , McGrath Emer R. , Jacobs Heidi I.L. , Satizabal Claudia L. , Ghosh Saptaparni , Rubinstein Zoe B. , Murabito Joanne M. , Sperling Reisa A. , Beiser Alexa S. , Seshadri Sudha
Published: December 2021

Background

Cognitively‐normal (CN) older women exhibit elevated tau‐PET signal in medial temporal and neocortical regions compared with men. The effect of menopause on tau deposition remains unclear. We explored menopausal status as a moderator of sex differences in tau deposition in middle‐aged adults.

Method

273 CN (Age=55yrs(±8), Female(n)=134, Post‐menopausal(n)=70) from the Framingham Study 3rd generation cohort underwent 18F‐Flortaucipir (FTP)‐PET and/or 11C‐Pittsburgh Compound‐B (PiB)‐PET scans. We examined FTP‐PET signal in four a priori regions that demonstrate large sex differences in CN older adults (entorhinal, rostral middle frontal, inferior parietal and lateral occipital). FTP‐PET and global PiB‐PET signal were referenced to cerebellar grey. Linear regression examined sex differences in each ROI, adjusting for age and PET camera. Separate models examined menopausal status (post‐menopause/pre‐menopause females), menopausal age (≤|>50 years), and interactions with APOEε4. Sensitivity analyses included age‐matched males (‘pseudo‐premenopausal’/‘pseudo‐menopausal’) against the menopause groups to account for confounds with chronological age.

Result

Middle‐aged females exhibited higher FTP‐PET signal in the inferior parietal, rostral middle frontal and lateral occipital regions than males by ∼0.04SUVr (p<0.009; Fig. 1). No sex or menopause differences were evident in PiB‐PET. Post‐menopausal females exhibited higher FTP‐PET signal in the lateral occipital lobe than pre‐menopausal (p=0.05; Fig. 2). Menopause age≤50 years corresponded with higher lateral occipital and rostral middle frontal FTP‐PET signal than >50years (p<0.05; Fig. 2). Post‐menopausal females maintained higher signal in lateral occipital, inferior parietal and rostral middle frontal regions compared with even age‐matched ‘pseudo‐menopausal’ males (Table 1). Finally, a significant menopause*APOEε4 interaction suggested that the menopause effect was only evident in APOEε4 non‐carriers, localized to the parietal lobe (p∼0.03; Fig. 3).

Conclusion

Sex differences in tauopathy are apparent in CN individuals approximately 20 years earlier than previously demonstrated. Our findings suggest that sex differences are exacerbated by menopause, particularly when the age‐at‐menopause is below 50 years. Chronological age did not appear to confound the results, as age‐matched males exhibited significantly lower tau signal. Finally, the effect of APOEε4 carriership may ameliorate menopause effects; only pre‐menopausal APOEε4 non‐carriers appeared to exhibit protective effects of circulating estradiol relative to post‐menopausal non‐carriers. Future work will need to identify direct hormonal contributions, the impact of surgery and hormone‐therapy.
Telememory – A systematic, automated, digital reminiscence therapy platform for patients with dementia: A pilot project
Authors: Grossberg George T , Arnold Eliot C , Bukowski Martin , Adams Angie C
Published: December 2021

Background

Reminiscence Therapy (RT) is a therapeutic modality for cognitive stimulation therapy. The difficulty employing this therapy is gathering personal and family memories to engage the patient in life‐review. Digital RT (DRT) bypasses these difficulties, allowing family to engage in the creation of digital content designed to highlight patient‐specific memories administered via internet and communication technology. The efficacy of DRT has been demonstrated in controlled studies with positive results when compared with traditional reminiscence therapy.[1] The focus is how DRT (a non‐pharmacological intervention) reduces dementia related behavior. Based on this previously published research, we share preliminary results utilizing a proprietary platform to administer DRT to dementia patients. We implemented DRT through a novel technology platform. The platform runs on Android‐based devices. The solution standardizes collection of patient biographical information through care team interaction. Digital artifacts (photos, music, videos) are assembled through proprietary interfaces to produce a patient‐centric DRT session. DRT sessions are shared with patient 3‐5 times per week, allowing patient to experience benefits of reminiscence therapy through an automated interface. Minimal on‐staff time is needed. Proprietary AI, which is currently being refined, records patient reactions to stimuli presented throughout each session, allowing future sessions to be tailored towards those stimuli producing the highest level of positive response. DRT was administered via the Telememory solution to five (5) patients at skilled nursing facilities. Empirical data concerning mood improvement was gathered remotely and onsite by Telememory and facility staff. Assistance from onsite facility staff was minimal, limited to the initiation of DRT sessions and patient observation. Results were positive. Patients demonstrated consistent mood improvement sessions. In some cases, mood improvement extended beyond treatment. Mood improvement and patient mental status was confirmed by Neuropsychiatric Index evaluations. The quality of outcomes improved with increased patient/family/caregiver memory data input. Patients experienced immediate and post‐treatment benefits as observed by onsite caregiver staff. Best results were achieved with closely curated content from each patient’s past. Highest cognitive stimulation and mood improvement occurred from the presentation of digital artifacts provided by family members and primary caregivers.
Elevated neurofibrillary tau levels emerge with subthreshold Aβ accumulation in Down syndrome
Authors: Zammit Matthew D , DiFilippo Alexandra H , Tullis Tyler , McVea Andrew K , Tudorascu Dana L , Laymon Charles M , Cohen Ann D , Zaman Shahid , Ances Beau M. , Hartley Sigan L , Johnson Sterling C. , Stone Charles K , Mathis Chester A , Klunk William E , Handen Benjamin L , Christian Bradley T
Published: December 2021

Background

Adults with Down syndrome (DS) are genetically predisposed to Alzheimer’s disease (AD) and accumulate beta‐amyloid plaques (Aβ) early in life. The aim of this study was to evaluate neurofibrillary tau deposition in DS between groups of Aβ negative (A‐) and subthreshold Aβ accumulators (subthreshold A+).

Method

A total of 130 adults with DS (age=36.5 [6.77] years) and 40 healthy, non‐DS sibling controls (43.2 [12.6] years) underwent T1w‐MRI, [C‐11]PiB and [F‐18]AV‐1451 PET scans. MRI images were processed using FreeSurfer v5.3.0 to generate ROI masks encompassing the Braak staging of tau pathology. PiB and AV‐1451 SUVr images were generated using a cerebellar gray matter reference region. Global Aβ burden was calculated using the amyloid load metric (AβL). Of the 130 DS adults, N=26 were classified as subthreshold A+ (13.3 < AβL < 20), and the remaining 104 were classified as A‐ (AβL < 13.3). AV‐1451 images were averaged for each group, and the difference was taken to generate a ΔSUVr image. Regional tau was assessed using AV‐1451 SUVr Z‐scores relative to the sibling control group. Partial volume correction was performed on AV‐1451 SUVrs in the Braak I‐II regions using the geometric transfer matrix method. Braak regional SUVr Z‐scores were then compared across the two groups using Student’s t‐tests while adjusting for imaging site. The analysis was then repeated using an age‐matched sample of A‐ (N=68) and subthreshold A+ (N=26) DS.

Result

The SUVr difference image revealed higher AV‐1451 uptake in Braak regions I‐III for the subthreshold A+ group (Figure 1). Student’s t‐tests revealed significantly higher AV‐1451 uptake in Braak regions I‐III for the subthreshold A+ group (Table 1). No difference in AV‐1451 uptake was observed between groups in Braak regions IV‐VI (Table 1). Higher AV‐1451 uptake in Braak regions I‐III was also observed in the subthreshold A+ group when compared to the age‐matched A‐ group (Table 2).

Conclusion

These results show that subthreshold Aβ in DS is accompanied by elevated tau in the early Braak stage regions. These findings indicate that there is a short latency between the onset of Aβ and the spread of neurofibrillary tau in DS.
The Global Council on Brain Health: Tailoring brain health guidance for the pandemic era
Authors: Chura Lindsay Rachel
Published: December 2021

Background

The Global Council on Brain Health (GCBH) recognizes people across the globe are interested in learning what they can do to maintain their brain health as they cope with the pandemic. With growing evidence that COVID‐19 harms brain health, the GCBH determined it was important to inform people about the impact and what if anything might be done about it.

Method

The GCBH has updated recommendations relevant to patient and caregiver advice to reflect the current challenges of living in a pandemic. This presentation will explore both the direct and indirect ways the virus impacts brain health and offers recommendations based upon the current state of the science on how to try to avoid the harms the pandemic poses. The GCBH considered which of their previous brain health recommendations they could make to foster brain health resiliency during the pandemic.

Result

Recommendations included: stay physically active, eat a healthy diet, stay socially connected, maintain a regular sleep schedule, stimulate your brain, take care of your mental health, pay attention to signs of ‘brain fog’, monitor changes in neurological health, and don’t put off necessary medical appointments.

Conclusion

This presentation will discuss the approach taken and lessons learned in adapting several years of brain health guidance for the COVID era. Living through this pandemic, even without infection, can adversely impact mental well‐being and ultimately brain health. Many people have been forced to change rituals and routines with substantially reduced social interaction under guidelines designed to reduce the spread of the virus. Moreover, COVID has had an undeniably huge negative impact on people living with dementia and the long‐term consequences will be topic of research for years to come.
Apathy as a treatment target in neurocognitive disorders: Clinical trial implications
Authors: Mortby Moyra E , Adler Lawrence , Agüera‐Ortiz Luis , Bateman Dan R , Brodaty Henry , Cantillon Marc , Geda Yonas E. , Ismail Zahinoor , Lanctôt Krista L. , Marshall Gad A , Padala Prasad R , Politis Antonis , Rosenberg Paul B. , Siarkos Kostas , Sultzer David L , Theleritis Christos
Published: December 2021

Background

Apathy is the most prevalent, stable and persistent neuropsychiatric symptom observed across the neurocognitive disorders spectrum and is linked to poorer disease outcome, reduced daily functioning and higher levels of caregiver distress, and an increased risk of mortality. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight an increased interest in and recognition of apathy as an important target for clinical intervention. We therefore conducted a comprehensive review and critical evaluation of recent advances to determine evidence‐based suggestions for future trial designs.

Method

A critical review of latest research on apathy as a treatment target in pre‐dementia and dementia populations by the Alzheimer’s Association International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS‐PIA) Apathy Workgroup. This review focused on 4 key areas: 1) mechanisms and biomarkers; 2) assessment; 3) treatment and intervention efficacy; and 4) pre‐dementia states.

Result

Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non‐pharmacological apathy treatment interventions. Areas of the literature requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms and biomarkers of apathy, and a carefully considered and well‐formed approach to the development of treatment strategies.

Conclusion

We have made much progress in better understanding the role of apathy in affecting the impact and course of neurocognitive disorders and are starting to see some successes in targeting new treatments. To advance the recognition of apathy as a treatment target for clinical trials, it is essential that a better understanding of the subdomains and biological mechanisms of apathy are achieved. We propose the utility of a comprehensive multi‐national longitudinal observational study of neuropsychiatric symptoms in which the study of apathy is incorporated.
Challenges of defining healthcare costs for people with mild cognitive impairment (MCI) based on the claim database analysis in Japan
Authors: Shibata Kai , Ariyoshi Koichi , Azuma Mie , Shiromi Kai , Hioki Shinya , Ishii Mika
Published: December 2021

Background

The earlier treatment for dementia is important when it is diagnosed. The annual healthcare costs for mild Alzheimer's disease (AD) has been reported to be approximately 250,000 JPY (equivalent to 2,400 USD) per person [1], but there were few cost studies associated with mild cognitive impairment (MCI). This study aimed to clarify the healthcare costs incurred for MCI using a medical claim database in order to find out the disease burden in the early stage of dementia.

Method

An administrative claim database of Diagnostic Procedure Combination provided by Medical Data Vision Co., Ltd. was used. Patients data with MCI (ICD‐10 code: F067) diagnosed between April 2008 and September 2018 were selected. The index date was the date of the first diagnosis of MCI, and the evaluation period was the period between the index date and the date of the diagnosis of dementia or the date of any dementia medication prescribed as the end of MCI stage. If no date was given above, the last day of visit to a psychiatric department or the date of death was taken. Patients diagnosed with dementia before the index date or patients with an evaluation period of fewer than 30 days were excluded. From the selected patients, we identified the evaluation period, actual treatment for MCI during that period, and treatment costs. Tableau (Tableau Software LLC. Seattle, WA, USA) was used for the analyses.

Result

The total number of patients with MCI whose medical costs could be assessed was 4,713. The mean and median duration of MCI were 574 and 351 days, respectively; most of these patients were later diagnosed with dementia. The mean annual healthcare costs per person were 118,257 JPY (median: 40,551. min: 0. max: 3,764,722.), in which monitoring or diagnostic examination was mainly claimed.

Conclusion

Healthcare costs associated with MCI were limited and lower than those associated with mild AD. [1] Kitamura S., Inoue S., Matsui D., Matsushita Y. Cost‐effectiveness analysis for memantine monotherapy in patients with moderate and severe Alzheimer’s disease. Japanese Journal of Geriatric Psychiatry 2014;25: 1361‐1373.
Memory assessment and dementia risk in the PREVENT Study
Authors: Parra Mario A , Muniz‐Terrera Graciela , Danso Samuel O. , Ritchie Karen , Ritchie Craig W.
Published: December 2021

Background

Promising memory markers for Alzheimer´s dementia (AD) tap into either relational (face‐name) or conjunctive (object‐colour) functions (Rentz et al., 2013). Whereas relational functions appear affected in the early symptomatic stages of AD, conjunctive functions have been found impaired in the pre‐symptomatic stages. Relational but not conjunctive functions are age sensitive. This can delay the detection of AD‐related impairments. No study to date has traced the progression or memory decline in people at risk of AD using these markers. This is an aim of the PREVENT study.

Methods

A cohort of 183 healthy adults with age ranging from 40‐60 years (M: 52) underwent assessment at baseline and two‐year follow up (T1). The assessment consisted of the neuropsychological test battery COGNITO (Ritchie et al., 2017), a demographic questionnaire, and four memory tests (relational: Virtual Reality Supermarket Trolley Task (VRST), Name‐Face Association Test (NFAT), and 4 Mountain Test (4MT), and conjunctive: Visual Short‐Term Memory Binding Test (VSTMBT)). Participants also underwent genetic testing to identify APOE genotypes. Risk profiles were defined by the present of Family History and APOE4, with High Risk subjects being positive to both, Middle Risk to either, and Low Risk to neither. Cross‐sectional and longitudinal comparisons were carried out within and across risk groups.

Results

Neither cross‐sectional nor longitudinal comparisons revealed differences across risk groups on the memory markers. Only the NFAT significantly correlated with age (p<0.01). The VRST and VSTMBT were not associated to the level of education while the NFAT and 4MT were (p<0.05). Correlations between baseline and T1 were large for all the tests. Performance on the VSTMBT did not correlate with that on any relational memory tasks. The VSRT and 4MT did reveal significant correlations (p<0.001).

Conclusion

We have identified an early time window in the ageing continuum where people at risk of dementia show intact cognitive functions known to be markers of AD. We have replicated the previously reported patterns of sensitivity to demographic variables (age and education) and confirmed their potential to dissociate trajectories of memory decline across constructs and risk profiles.
Behavioural and psychological symptoms of dementia in aboriginal australians
Authors: Lavrencic Louise , Yong Zechariah , Daylight Gail , Broe Gerald A , Draper Brian , Radford Kylie
Published: December 2021

Background

Behavioural and Psychological Symptoms of Dementia (BPSD) and Neuropsychiatric Symptoms (NPS, in people without dementia) have not been examined in the Aboriginal Australian population despite high rates of dementia and cognitive decline. BPSD/NPS contribute significantly to poorer wellbeing, institutionalisation, and adverse outcomes. This study aims to identify the characteristics and factors associated with BPSD/NPS in older Aboriginal Australians.

Method

Data were from the Koori Growing Old Well Study, a longitudinal, population‐based study with Aboriginal Australians from 5 partnering communities in New South Wales (n=336 baseline including n=153 with medical assessment). Participant, care person and medical interviews were carried out. Baseline BPSD/NPS were classified using the Cambridge Behavioural Inventory‐Revised (CBI‐R) and social and clinical predictors were collected. Logistic regression analyses examined associations with severe BPSD/NPS.

Result

CBI‐R data were available for n=132 (mean age= 67, SD= 6.6; 46% male). The prevalence of one or more NPS was high (66%), with 74% of mild cognitive impairment (MCI) and 100% of people with dementia experiencing symptoms. Patterns of behaviour change indicated that mood symptoms were prominent in MCI/mild dementia, symptoms of apathy worsened with dementia severity, and abnormal beliefs were more prominent in moderate/severe dementia. Stroke history (OR=4.4) and living in residential aged care (RAC; OR=10.8) were associated with severe BPSD/NPS. When presence of a dementia diagnosis was added to the model, only RAC (OR=5.5) and dementia presence (OR=5.8) remained significant.

Conclusion

The prevalence of BPSD/NPS is high in Aboriginal communities, linked to the high rates of cognitive decline. Characterising the pattern and predictors of BPSD/NPS is critical for early intervention and support. Future research should validate culturally‐relevant assessment and models of care for BPSD/NPS.
Consumption of ultra‐processed food and cognitive decline among older adults with type‐2 diabetes
Authors: Weinstein Galit , Vered Shiraz , Ivancovsky‐Wajcman Dana , Zelber‐Sagi Shira , Ravona‐Springer Ramit , Heymann Anthony , Beeri Michal Schnaider
Published: December 2021

Background

Ultra‐processed foods (UPF) are ready‐to‐eat/heat foods that derive from a series of industrial processes. These products constitute a large and increasing amount of the food supply in high and middle‐income countries. Accumulating evidence point to an association of UPF intake with increased mortality and adverse health outcomes, including cardiovascular and metabolic diseases. However, whether UPF consumption is associated with cognitive function is not clear. We investigated the associations between UPF intake and cognitive decline, in a cohort of older adults at high‐risk for dementia due to type‐2 diabetes (T2D).

Method

The study sample included initially non‐demented T2D older adults (≥65y), from the Israel Diabetes and Cognitive Decline (IDCD) study, who had complete information on nutrition at baseline and at least three cognitive assessments (mean follow‐up 5.3±1.5y). Nutritional intake was evaluated by a validated Food‐Frequency Questionnaire and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption, first as overall UPF intake and then for specific food groups. Global cognitive functioning and four cognitive domains (episodic memory, working memory/attention, semantic categorization, and executive functions) were assessed. Mixed effect models were used to examine the link between UPF intake (top vs. bottom quartiles) and change in cognitive function while adjusting for age, sex, education, smoking, physical activity, BMI, HbA1C, duration of diabetes, total cholesterol and blood pressure.

Result

Of the total sample (N=578; mean age at baseline 71.3±4.5y, 61% men), 144 (top quartile) consumed >31% kcal from UPF out of total kcal. Total UPF consumption was not related to cognitive function. However, consumption of ultra‐processed fat (e.g. mayonnaise) was associated with faster decline in global cognition, executive function and memory (ß=‐0.028±0.010; p=0.009, ß=‐0.031±0.014; p=0.022 and ß=‐0.035±0.017; p=0.046, respectively). Additionally, increased intake of ultra‐processed meat (e.g. sausages) was associated with a faster decline in executive functions (ß=‐0.029±0.013; p=0.031). UPF derived from dairy products and carbohydrates were not associated with cognitive change.

Conclusion

This pioneering study suggests a possible association of ultra‐processed meat and fat intake with accelerated cognitive decline in older individuals with T2D, independently of sociodemographic, lifestyle, cardiovascular and T2D‐related factors.
The relationship between cognitive and social leisure activities across the lifespan and neural markers for brain health: A systematic literature review
Authors: Duffner Lukas , de Jong Nathan , Backes Walter H , Jansen Jacobus FA , de Vugt Marjolein , Deckers Kay , Koehler Sebastian
Published: December 2021

Background

Cognitive and social leisure activities (CA/SA) as well as social network size (SNS) have been associated with performance on cognitive tasks and lower dementia risk. However, the neural mechanisms behind these associations remain unclear. Therefore, this systematic literature review aims at summarizing the available evidence on these associations across the adult lifespan.

Method

MEDLINE, PsychINFO, CINAHL and the Cochrane Library of Controlled Trials were searched for potential publications until January 2021. Eligible studies included those with cognitively normal individuals older than 18 years, and assessed the direct association between CA/SA or SNS and brain structure. CA/SA were defined as those cognitively and/or socially stimulating activities being performed for the sake of pleasure. Eligible outcome measures included magnetic resonance imaging (MRI) of macro (grey/white matter volumes) and micro (diffusion tensor imaging) structure, or computerized tomography (CT). Both observational and (quasi)experimental designs were included. Study‐quality was assessed using the NIH tool for study quality appraisal and the Newcastle‐Ottawa Scale. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. A full protocol is available in PROSPERO (CRD42020193278).

Result

6115 unique abstracts were identified and screened by two independent raters. Sixty‐six full‐text articles were retained for further appraisal, of which thirty‐five (0.6%) were included for qualitative analysis. Of those, 20 cross‐sectional, 4 cohort and 3 experimental studies investigated the association between CA/SA and brain structure. Eight cross‐sectional studies investigated the relationship between social network size and brain structure. All studies included in this review used structural MRI (3 used DTI) as outcome measure. In the majority of studies, CA/SA and SNS showed associations with structural brain MRI markers. Detailed results of this ongoing review and possible meta‐analysis will be presented.

Conclusion

CA and SA are associated with structural MRI markers.
Dementia care in Taiwan during COVID‐19
Authors: Yoon Grace H , Shyu Yea‐Ing L , Lin Paige
Published: December 2021

Background

Taiwan has been bolstering dementia care policy with the concern of reaching the ‘super‐aging’ mark by 2025. Taiwan’s success in containing the COVID‐19 pandemic involves focused, timely interventions in preventive measures, including policies targeting people living with dementia and their caregivers. This review presents key dementia policy interventions achieved during the pandemic.

Method

A scoping review of published academic, media and grey literature was conducted. We extracted relevant information pertaining to dementia care during the COVID‐19 pandemic and summarized the data in a narrative format.

Result

Taiwanese government has implemented a policy in April 2020 that restricted visitations to long‐term care facilities, which continues today. Since the start of the pandemic, one nurse and no individuals with dementia living in long‐term care facilities has been infected. A landmark decision was made in April 2020 to ban penalization of people with dementia for violation of the epidemic prevention regulation (e.g., wearing a mask) if they have documentation of disability. This was possible due to the strong, continued advocacy from the Taiwan Alzheimer’s Disease Association (TADA). TADA provided critical resources to the dementia community by releasing online videos to teach patients how to protect themselves and others during the pandemic, such as mask wearing and handwashing. TADA’s Reference Handbook of Dementia Care Responding to COVID‐19was well‐received by the Health Promotion Administration of the Ministry of Health and Welfare, who forwarded the handbook to all local governments and shared these videos on its national official website. There are government‐sponsored facilities across the districts of Taipei City that encourage people with dementia to participate in local activities during the pandemic.

Conclusion

In Taiwan, national public health policies quickly came into place since the beginning of the pandemic to curb the spread of COVID‐19 infection in elderly care settings impacting dementia care. Patient advocacy groups have played an important role in providing resources and support to the dementia community. Taiwan’s recent demonstration of quick policy reactions and public‐private partnerships to protect people with dementia and their caregivers provide an effective dementia care model for future response measures.
Sex and ApoE‐4 interactions on development and severity of psychosis in AD
Authors: Tan Yu Bin , Fornazzari Luis , Dissanayake Andrew S. , Churchill Nathan W , Schweizer Tom A. , Munoz David G. , Fischer Corinne E.
Published: December 2021

Background

Nearly half of all Alzheimer’s Disease (AD) patients experiences psychosis at some point in their disease trajectory. Kim et al. (2017) found a sexual dimorphism in AD psychosis where the ε4 allele may play a larger role in influencing psychosis development in females with Lewy body (LB) pathology.

Method

We investigated the effect of sex and ApoE‐4 status on age, presence and severity of psychotic symptoms on a clinical cohort using data from the National Alzheimer’s Disease Coordinating Centre (Figure 1). The non‐psychotic group (AD‐P) was compared against each of the overlapping diagnostic groups – psychotic (AD+P), delusion (AD+D) and hallucination (AD+H).

Result

We found a significant association between ε4 homozygotes and AD+P (OR = 1.08, p =. 017) and AD+D (OR = 1.09, p = .007). There was also a significant association between ε4 heterozygotes and AD+P (OR = 1.09, p = .004) and AD+D (OR = 1.08, p = .012). In males, the likelihood of having two copies of ε4 was increased in AD+P (OR = 1.10, p = .034) and AD+D (OR = 1.13, p = .006). The likelihood of having one copy of ε4 was also increased in AD+P (OR = 1.10, p = .030) and AD+D (OR = 1.10, p = .028). In females, the likelihood of having one copy of ε4 was increased in AD+H (OR = 1.10, p = .033). Participants who were female and homozygous for ε4 had a predicted increase of 0.388 in the log‐odds of being in a more severe category for delusions (95% CI: 0.016 ‐ 0.759, p = .041) and hallucinations (95% CI: 0.011 ‐ 1.264, p = .046).

Conclusion

Our findings show that the presence of ApoE‐4 increases the risk of psychosis in clinically diagnosed AD patients. Moreover, there are differential associations between sex, ApoE‐4 status and psychotic manifestations. The fact that we did not find an increase risk of psychosis among female homozygous ApoE‐4 carriers may be explained by the fact that we did not stratify by Lewy body pathology (Tsuang et al., 2005).
Impact of mild behavioral impairment on longitudinal changes in cognitive performance
Authors: Rouse Hillary J , Small Brent J , Ismail Zahinoor
Published: December 2021

Background

Recent research has developed a better appreciation for non‐cognitive factors, such as neuropsychiatric symptoms (NPS), as early indicators for dementia. This has led to the development of criteria for mild behavioral impairment (MBI), or the late‐life onset of NPS. MBI has been associated with a unique cognitive phenotype, but research on longitudinal changes is limited. The goal of this study is to examine if MBI influences changes in cognitive abilities among older adults who are cognitively healthy (CH) or have mild cognitive impairment (MCI).

Method

Secondary data analysis of participants (n=17,291) from the National Alzheimer’s Coordinating Center who were CH (n=11,771) or diagnosed with MCI (n=5,520). Almost 25% of the sample met the operationalized diagnostic criteria for MBI (n=4,274). Cognitive performance was evaluated using tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed.

Results

Cross‐sectionally, persons with MBI performed worse on tasks of attention, episodic memory, executive function, language, visuospatial ability, and processing speed compared to people without MBI. There were no significant interactions present between MBI and MCI on any of the tasks. Longitudinally up to 14 years, persons with MBI saw a greater decline on tasks of attention, executive function, language, episodic memory, and processing speed compared to individuals without MBI. Further, older adults with MBI performed significantly worse across time on tasks of executive function, language, and processing speed when compared to CH older adults without MBI. Persons with MBI and MCI performed significantly worse across time on tasks of executive function, language, processing speed, and visuospatial ability when compared to those with only MCI.

Conclusion

Older adults with MBI performed worse on all cognitive domains, compared to those without MBI. Additionally, CH older adults with MBI saw a greater decline across time in the domains of executive function, language, and processing speed. In the MCI group, MBI was associated with a greater decline in all of these domains in addition to visuospatial ability. The results provide support for unique cognitive phenotypes for MBI in CH older adults and MCI, that may be indicative of preclinical and prodromal symptoms of dementia.
Cognitive intraindividual variability as a biomarker for functional declines in the Texas Alzheimer’s Research and Care Consortium (TARCC) Longitudinal Hispanic Cohort
Authors: Scott Bonnie M. , Royall Donald R. , Hilsabeck Robin C.
Published: December 2021

Background

While intraindividual variability (IIV) in cognitive performance has been associated with increased risk for cognitive decline, the relative predictive utility of IIV‐across versus IIV‐within different cognitive domains remains unknown. Given that cognitive IIV has also been linked to age‐related reductions in white matter integrity, the current study aimed to determine if IIV‐within a “frontal‐subcortical” domain may be a more robust predictor of functional declines over time than IIV‐across cognitive domains.

Methods

Participants included 651 controls, 211 MCI and 218 AD patients enrolled in the TARCC Hispanic Longitudinal Cohort. Mixed Linear Modeling was used to examine the fixed effects of static predictors (i.e., age, education, gender, ethnicity, APOE genotype, cognitive status) at baseline, and the fixed and random effects of time‐varying covariates (i.e., depression, pulse pressure, IIV‐across domains, and IIV‐within the frontal‐subcortical domain) on changes in functional independence over 5 years.

Results

Age, education and ethnicity moderated the relationship between APOE genotype, baseline cognitive status and declines in functional independence over time. Overall, greater pulse pressure, IIV‐across domains and IIV‐within the frontal‐subcortical domain were all associated with larger decrements in functional independence over time. Although increases in IIV‐across domains were primarily driven by increases in IIV‐within the frontal‐subcortical domain over time, the former emerged as a stronger predictor of functional independence than the latter. Gender and education significantly influenced individual differences in rates of change over time, while the effects of IIV‐across domains and IIV‐within the frontal‐subcortical domain on functional declines differed from person‐to‐person. The addition of cognitive IIV predictors significantly improved model fit with a 1498.3 reduction in ‐2LL (p < 0.001). The final model accounted for 97.8% of the variance in functional independence over time.

Conclusions

Results suggest that IIV‐across domains may be a robust biomarker of subsequent declines in functional independence and changes in this metric are primarily driven by increasing variability across tasks dependent on frontal‐subcortical circuitry. Findings also highlight important considerations for the development of future clinical trials aimed at early prevention and treatment, including the significance of demographic and clinical characteristics in moderating the risk of decline in functional independence over time.
A data‐driven examination of clustering of apathy and depression symptoms in people with dementia
Authors: Da Silva Miguel Vasconcelos , Melendez‐Torres G.J. , Testad Ingelin , Ballard Clive , Creese Byron
Published: December 2021

Background

Apathy is one of the most common Neuropsychiatric Symptom (NPS) and is associated with poor clinical outcomes. Apathy remains under‐researched and its medical classification remains unclear, potentially associated with the fact that apathy is commonly a comorbidity with depression. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies.

Method

Using latent class analysis (LCA) we analysed data from the KCL Care Home Research Network study with 349 participants (an observational study of people living with dementia in care homes). The aim was to understand how apathy and depression phenotypes cluster together. Apathy and depression were defined on the basis of item G (Apathy) and D (Depression) of the NPI‐NH scale, combining the 7 apathy subquestions with the 8 depression subquestions, rated as yes or no. Predictors of class membership were then analysed, including other NPS, demographics, medication and Clinical Dementia Rating (CDR).

Result

The LCA analysis showed a 4‐cluster group which was considered the best model: No symptoms, predominantly depression, apathy/depression, and a predominantly apathy group. Those in the apathy/depression class were more likely to experience psychosis symptoms compared to the no symptoms class, whilst those in the predominantly apathy class were more likely to have a higher CDR score compared to the no symptoms class.

Conclusion

Using a data driven method, we show distinct clustering of apathy and depression symptoms in this cohort. There was evidence that these clusters have different clinical associations which may help inform diagnostic categories for research studies and clinical practice. Potentially, the four subtypes may be used in future studies to further evaluate their utility in biomarker studies in dementia.
Using a virtual reality path integration task to investigate entorhinal functioning in individuals with and without subjective cognitive decline
Authors: Alkan Merve , Bierbrauer Anne , Kunz Lukas , Axmacher Nikolai , Jessen Frank
Published: December 2021

Background

The entorhinal cortex (EC) contains spatially modulated cells, so called grid cells, and plays a central role in spatial navigation. Studies show that tauopathy in the EC is already observed in the early stages of Alzheimer's disease (AD) and is responsible for impairments in spatial memory performance. Moreover, recent studies demonstrate that young, healthy volunteers with the APOE‐ε4‐allele, a genetic risk factor for AD, show impaired grid‐like representations in the EC and reduced path integration performance in environments without spatial cues. People with subjective cognitive decline (SCD) perceive a subjective deterioration in their cognitive memory performance with unimpaired performance on standardized neuropsychological tests. SCD corresponds to the recently defined stage 2 of AD and is also a risk factor for dementia. Here, we tested whether subjects with SCD show path integration impairment, presumably related to malfunctioning in the EC.

Method

68 participants (31 SCD patients recruited through a memory clinic, age: 68.8 ± 9.2; 37 controls without SCD, age: 69.1 ± 7.9) performed a path integration task on a laptop. In addition, a neuropsychological test (CERAD+) was carried out to rule out an objective cognitive impairment.

Result

The two groups did not differ in age, sex, medical history and number of educational years. We replicated previous findings indicating better path integration performance with spatial cues such as boundaries and landmarks (F(2,128) = 20.83, P < 0.001). In addition, we showed that women performed worse than men (F(1,64) = 6.00, P = 0.017) and that path integration performance declined with increasing age (F(1,64) = 32.14, P < 0.001). There was no significant difference in performance between SCD and controls (F(1,64) = 2.20, P = 0.143).

Conclusion

Generally, SCD was not associated with lower path integration performance. We are in the process of characterizing the sample based on plasma amyloid beta 42/40, NFL, pTau and APOE genotype to test, if AD biomarkers and genetic risk factors are associated with path integration performance.