bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting cortical thickness with [18F]flortaucipir PET: A longitudinal MRI study
Authors: Visser Denise , Ossenkoppele Rik , Bosch Iris W.M. , Brouwer Iman , Tuncel Hayel , Coomans Emma M. , Rikken Roos M. , Mastenbroek Sophie E , Verfaillie Sander C.J. , Golla Sandeep S.V. , Barkhof Frederik , van der Flier Wiesje M. , van Berckel Bart N.M. 
Published: June 2023

AbstractBackgroundThe association between tau pathology and neurodegeneration (atrophy) in Alzheimer’s disease (AD) is not fully understood. This study aimed to investigate whether tau pathology is associated with concurrent and longitudinal cortical thickness in individuals along the AD continuum.MethodWe included 92 amyloid‐positive cognitively impaired individuals (age 65±7, 48% female, MMSE 23±4) with AD dementia (n = 73) or mild cognitive impairment due to AD (MCI, n = 19) and 61 cognitively normal individuals (CN; age 66±8, 48% female, MMSE 29±1) with subjective cognitive decline (SCD, n = 55, 19 amyloid‐positive) or healthy controls (HC, n = 6, amyloid‐status unknown). All participants underwent dynamic [18F]flortaucipir PET and structural 3T‐MRI at baseline. A subset underwent two‐year follow‐up structural 3T‐MRI (CN: n = 35, time‐interval 24±8 months; AD: n = 26; time‐interval 28±4 months). Parametric [18F]flortaucipir binding potential (BPND) images were generated using receptor parametric mapping (cerebellar gray matter reference region) to quantify tau pathology. Cortical thickness (over time) was measured using Freesurfer (version 6.0.1). Regional associations between [18F]flortaucipir BPND and cortical thickness were assessed using linear mixed models in three commonly used a priori defined regions‐of‐interest, including entorhinal, middle‐and inferior temporal, and neocortical areas. Models were adjusted for age, sex and amyloid status (in case of CN individuals).ResultFor cognitively impaired individuals, higher [18F]flortaucipir BPND (in all three regions) was associated with lower concurrent cortical thickness in the entorhinal cortex [Table‐1&Fig‐1]. Higher middle‐ and inferior temporal and neocortical BPND was associated with cortical thinning over time within the same region (intra‐regionally). Higher middle‐ and inferior temporal BPND additionally showed associations with cortical thinning over time in the neocortex (inter‐regionally). For cognitively normal individuals, we found no associations between [18F]flortaucipir BPND and cortical thickness (over time) [Table‐1&Figure‐1].ConclusionTau pathology is associated with both concurrent and longitudinal atrophy in a region‐specific manner in cognitively impaired individuals (MCI/AD), but not in cognitively normal individuals (HC/SCD). The regional‐specificity of these associations might suggest that there are similarities between tau‐related progression patterns and patterns of neurodegeneration. Taking into account a temporal delay between the development of region‐specific tau pathology and neurodegeneration, this potentially suggests that tau pathology is a (partial) driver of neurodegeneration in AD.
The effect of virtual reality on executive function in older adults with mild cognitive impairment: A systematic review and meta‐analysis
Authors: Lai Frank Ho‐yin , Yu Hailey Dan , LI Xun 
Published: June 2023

AbstractBackgroundVirtual reality (VR) ‐ a computer simulation of a real or imagined three‐dimensional (3‐D) environment, which allows users to have the same experiences they would get in a similar real situation, has stimulated the interest of researchers and clinicians since its first use in 1994. Compared to traditional pen‐and‐paper training, it is symbolized as a systematic and controllable intervention that makes use of data visualization and provides immediate feedback based on the participants’ performance. VR is usually categorized into three types according to the form of connection with the physical world, and includes non‐immersive, semi‐immersive, and full‐immersive VR.MethodThis review aimed to summarize the currently available premium evidence to determine the effect of virtual reality (VR) on executive function (EF) in older adults with mild cognitive impairment (MCI), and to detect what level of immersive VR would be the most beneficial. Five electronic databases, namely, PubMed, Embase, PsycINFO, CINAHL and Cochrane Library were searched. Our research team screened the studies and extracted data according to our inclusion criteria. The methodological quality of each study was rated using the PEDro scale. When three or more studies reported the same outcome, a meta‐analysis was conducted using Review manager 5.4.1ResultFinally, 14 randomized controlled trials with a total of 518 participants were included. VR training had an overall positive effect on cognitive flexibility, global cognitive function, attention, and short‐term memory compared to the control groups. Additionally, semi‐immersive VR was more effective in improving cognitive flexibility compared to the other two types of VR. The application of non‐immersive level of VR had a significant effect on global cognitive function, attention, short‐term memory, and cognitive flexibility.ConclusionVR may be effective in improving EF in older adults with MCI. However, the level of immersive VR that would be the most beneficial on EF still needs to be investigated with a greater number of well‐designed studies.
Changes in serum urate and body weight interact to affect cognitive decline rates of community‐dwelling older adults
Authors: Nelson Kendra L , Cheatham Carol L , Voruganti Saroja 
Published: June 2023

AbstractBackgroundSeveral innate and environmental factors affect the rate and degree of cognitive decline with each factor representing a potentially valuable intervention point to slow progression of this decline. Serum urate, a product of purine metabolism and potent antioxidant, and weight loss have been associated with cognitive decline. The aim of this study was to determine the relation among urate, body weight, and their interaction with cognitive function.MethodsIn the context of a larger study, 133 adults aged 65‐80 at baseline (mean baseline age 72.7 years, 56.5% male) were recruited to participate in a double‐blind, randomized controlled trial. The Montreal Cognitive Assessment (MoCA) was administered to assess cognitive function. Those with MoCA scores >25 were considered cognitively typical, whereas those with MoCA scores below this threshold were deemed to be experiencing mild cognitive decline (MCD). The cognitively typical group was instructed to maintain their regular diet and served as a reference, whereas MCD groups were randomized to receive either 35mg lyophilized wild blueberries or dextrose (serving as control) daily in addition to their regular diet. MoCA, anthropometric measures, and serum were collected at baseline and repeated at 3 and 6 months. The statistical analysis was performed using MiniTab v.19.ResultsA regression‐based analysis showed that changes in serum urate were positively associated with changes in MoCA scores (ß = 0.94, SE = 0.47, p < 0.05) at 6 months. Groupwise analyses showed that changes in MoCA scores were not correlated with changes in urate or body weight in individuals with typical cognition or those in the blueberry group. However, in the control group, changes in serum urate (ß = 1.96, SE = 0.92, p<0.05), changes in body weight (ß = ‐0.31, SE = 0.13, p<0.05), and interaction between urate and body weight significantly impacted the change in MoCA scores. (ß = 0.663, SE = 0.20, p<0.05). Individuals with increased urate and decreased body weight showed less cognitive decline as compared to those who had weight gain and decreased urate.ConclusionOur findings show that changes in urate and body weight interact with each other to significantly impact changes in cognitive function.
Tau deposition in the locus coeruleus and depression in cognitively unimpaired older adults
Authors: Kim Min Jung , Yi Dahyun , Byun Min Soo , Jung Joon Hyung , Kong Nayeoung , Jung Gijung , Lee Jun‐Young , Lee Yun‐Sang , Lee Dong Young 
Published: June 2023

AbstractBackgroundDepression is a common manifestation of Alzheimer’s disease (AD) and frequently observed at the early phase of the disease. Several postmortem studies demonstrated that tau deposition was found at the brainstem nuclei including the locus coeruleus (LC) and dossal raphe nucleus (DRN) (3, 4), even before early Braak stages of neurofibrillary tangle pathology. Given the disturbance of monoaminergic system is related to depression in general, tau deposition in the LC or DRN may underlie depression in late‐life, as suggested in a couple of postmortem studies. In this context, we tried to examine the hypothetical association between in vivo tau depostion at the brain stem monoaminergic nuclei and depression in cognitively unimpaired older adults.MethodA total of 69 cognitively unimpaired older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) were included. All participants underwent comprehensive clinical assessment including the Hamilton Rating Scale for Depression (HRSD) and [18F] AV‐1451 positron emission tomography. Tau deposition in the LC and DRN was measured using the Harvard Ascending Arousal Network Atlas (AAN). Tau deposition in the pons was also assessed as a non‐monoaminergic control for comparison. Age, education, sex, and apolipoprotein E ε4 positivity were controlled as covariates in the analyses for the association between brain stem tau and HRSD score.ResultTau deposition in the LC was significantly associated with HRSD total score (β = 3.861, P = .009). In contrast, there was no significant association between tau deposition in the DRN and HRSD score (β = 2.229, P = .090). Tau deposition in the pons was also not related to HRSD score (β = 1.632, P = .207).ConclusionThe findings support the possibility that alteration of the noradrenergic neurons in the LC by tau pathology may underlie depressive manifestation in cognitively unimpaired older individuals.
Reactive astrocytes as imaged with 11C‐DED in patients with different dementia disorders
Authors: Chiotis Konstantinos , Jelic Vesna , Rodriguez‐Vieitez Elena , Savitcheva Irina , Wall Anders , Antoni Gunnar , Nordberg Agneta K 
Published: June 2023

AbstractBackgroundNeuroinflammation, which receives ever increasing interest in neurodegenerative diseases, comprises a heterogeneous cascade of events that are thought to be related to the downstream neurodegeneration. The aim of this study was to evaluate the binding of 11C‐Deuterium‐L‐Deprenyl PET (DED) as a measure of reactive astrocytes in patients with different dementia disorders, and to assess its association with other disease biomarkers.MethodEleven patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA, n = 5) and behavioral variant of frontotemporal dementia (bvFTD, n = 6) were recruited. All patients had a cerebrospinal fluid biomarker profile that was inconsistent with Alzheimer’s disease (AD) or a negative amyloid‐β PET scan. The imaging protocol included 11C‐DED‐PET, 18F‐FDG‐PET, and a 3D T1 MRI. A group of amyloid‐beta positive patients with AD (n = 20) that underwent similar investigations were used for comparison. Z‐scores were created for 11C‐DED binding (Patlak slopes) and tracer relative delivery (R1 parameter) relative to that of healthy controls (HC; n = 20), for assessing the load of reactive astrocytes and cerebral perfusion, respectively.ResultThe patients with svPPA and bvFTD showed significantly higher 11C‐DED binding in frontotemporal areas, compared to HC. Patients with AD showed significantly higher 11C‐DED binding in temporo‐occipital areas, compared to HC. The regional distribution of 11C‐DED binding in the patients with svPPA and bvFTD was consistent with the expected underlying pattern of neurodegeneration in those disorders, although the load of binding was heterogeneous across patients with the same clinical diagnosis.ConclusionReactive astrocytes appear to be a common feature of different dementia disorders, although the regional pattern of reactivity differs. Ongoing work evaluates the relationship between patterns of reactive astrocyte activation, cerebral perfusion, glucose metabolism, atrophy, and cognitive performance.
Tau‐PET in retired contact sport athletes
Authors: Vasilevskaya Anna , Taghdiri Foad , Multani Namita , Ozzoude Miracle , Tarazi Apameh , Khodadadi Mozhgan , Wennberg Richard , Rusjan Pablo , Houle Sylvain , Green Robin , Colella Brenda , Blennow Kaj , Zetterberg Henrik , Karikari Thomas K , Mikulis David , Davis Karen Deborah , Tator Charles , Tartaglia Carmela 
Published: June 2023

AbstractBackgroundLong term effects of concussions and sub‐concussions in athletes can include delayed neurodegeneration as seen in Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). The PET tracer [18F]AV1451 has high affinity and selectivity for paired helical filament‐tau in vivo, the pathological form of tau in CTE and AD. The aim of this study was to assess the effect of tau‐PET binding on brain atrophy in former contact sports athletes and evaluate differences between subjects with and without tau‐PET binding.Method31 retired athletes (age:53±15; sex: 29M, 2F; concussions/athlete: 7±6) negative for AD (CSF: p‐tau <68 pg/mL and ATI >0.8 and/or normal range of plasma p‐tau181) and 54 normal controls (age: 50±13) were included. All athletes completed MRI, [18F]AV1451 tau‐PET, the Sport Concussion Assessment tool 2 (SCAT2) and the Personality Assessment Inventory (PAI) depression and anxiety scales. Tau‐PET standardized uptake value ratios (SUVR) images were created using cerebellar gray matter (GM); tau‐PET positivity was set to ≥1.30 SUVR. Normal control MRI scans were used to create age/intracranial volume corrected GM volume maps.ResultGM volumes were significantly lower in tau‐PET positive voxels in retired athletes ≥40 y.o. (N = 25; ‐0.48±0.40 vs. ‐0.42±0.41; p = .02) and there was a trend for lower GM volumes in tau‐PET positive voxels across athletes of all ages (N = 30; ‐0.40±0.42 vs. ‐0.35±0.41; p = .09), compared to tau‐PET negative voxels. Mean tau‐PET SUVR values in the cortical GM were used to divide retired athletes into tau‐PET positive (N = 20; SUVR ≥1.30) and negative (N = 11; SUVR <1.30) groups. The tau‐PET positive group did not differ in age (52±16 vs. 56±12; p = .4) or concussion number (9±7 vs. 7±5; p = 1.0) from the tau‐PET negative group; the tau‐PET positive group had significantly higher SCAT2 symptom severity (28.26±25.15 vs. 8.89±12.67; p = .01), PAI anxiety t‐scores (49.90±11.25 vs. 42.55±4.13; p = .01), and a trend for higher PAI depression t‐scores (54.75±16.58 vs. 47.09±8.08; p = .095), compared to the tau‐PET negative group.ConclusionTau‐PET may be useful for identifying those at risk for delayed neurodegeneration. Older athletes showed relatively greater brain atrophy in tau‐PET positive regions, suggesting that detection of tau‐PET at a younger age may enable interventions to prevent future degeneration.
Consumption patterns of dementia patients compared to the MIND diet
Authors: Waterman Anna , Labyak Corinne A , Sealey‐Potts Claudia 
Published: June 2023

AbstractBackgroundIt is well‐documented that nutrition plays a role in the development and the progression of dementia. There have been numerous suggestions on how to combat this issue from the pre‐diagnosis stage and throughout as nutritional deficiencies and malnutrition persist. Certain dietary patterns have been shown to be protective against this disease, namely the MIND diet. There is limited data on the current intake of individuals living with dementia therefore it is important to identify nutrition patterns in order to improve outcomes.MethodResearchers compared the dietary intake of diagnosed dementia patients compared to the dietary pattern recommended in the MIND diet. Dementia caregivers filled out food frequency questionnaires (FFQ) for loved ones with dementia on recent nutrition intake. Current intake was compared to the MIND diet categories for adequacy.ResultCaregivers (n = 28) completed FFQs on the eating patterns of respective dementia participant. Compared to the MIND diet serving recommendations, most participants reported under consumption of whole grains, leafy vegetables, and nuts, and over consumption of poultry, other vegetables, fast/fried foods, and cheese. Participants adhered to the recommendations for red meat, and all (100%) reported consumption patterns of steak, hamburgers and roast beef as less than 4 times per week. Fifty‐two percent reported fish consumption of one week or less; 50% ate 1 serving of nuts; 46.7% consumed the recommended amount of beans per week, and only 2 individuals reported alcohol consumption and it was kept to 1 serving per day. Pattern for frequencies for berries consumption was split evenly: 29.4% met the recommendation for consumption, while 29.4% reported lower than recommended consumption of this food item.ConclusionResults indicate that individuals with dementia are eating well below the recommended levels of suggested foods in the MIND diet. Excess consumption of items that should be limited was observed. These findings indicate a call to action for input from Registered Dietitians to counsel patients and caregivers after dementia diagnosis.
Are lifestyle factors and mental attitude 30 years earlier associated with being a 90+ SuperAger? Results from the 90+ study
Authors: Biswas Roshni , Kawas Claudia H. , Paganini‐Hill Annlia , Corrada María M. M. 
Published: June 2023

AbstractBackgroundIndividuals with superior cognitive performance despite older age are known as SuperAgers. However, gaps in our knowledge of factors related to the ability to maintain this superior level of cognition remain. Our aim was to identify lifestyle factors and mental attitudes 30 years earlier that were related to superior cognition in the oldest‐old.MethodParticipants of The 90+ Study, a population‐based longitudinal cohort of people aged 90+, are survivors from the Leisure World Cohort Study (LWCS). We assigned a participant’s cognitive diagnosis during a multidisciplinary consensus conference after their death. We analyzed data from participants without dementia who had an evaluation within a year of death. Individuals who scored ≥28 in their last Mini Mental State Examination within one year to two months before death, were categorized as SuperAgers (SA) and the rest as non‐SuperAgers. At the time of enrollment into the LWCS, 30 years earlier, all participants completed a questionnaire on lifestyle factors (body mass index, physical activity, smoking habits, alcohol intake) and seven positively worded items from the Zung self‐rating depression scale. To assess the relationships between being a SA and lifestyle and positive mental attitudes, we calculated odds ratios (OR) and 95% confidence intervals using multiple logistic regression.ResultsParticipants were 317 individuals (102 men and 215 women) with a mean age at the last visit of 96.6±3.3 years. Of them, 120 participants (37.8%) were identified as SA. Women and younger individuals were more likely to be SA while college education was unrelated (Table). Lifestyle factors and positive mental attitude were not associated with being a SA, although a greater proportion of SA tended to have healthful lifestyle habits, with normal body mass index, one or more hour of daily physical activity, and in the highest tertile for positive mental attitude (Table).ConclusionFactors like higher education, positive lifestyle choices and positive mental attitude, all related to living longer in this cohort, were not related to superior cognitive performance after ages 90 and older. Future research should try to identify other characteristics that may distinguish oldest‐old SuperAgers.
Dietary sulfur amino acid restriction to prevent Alzheimer’s Disease
Authors: Sambamurti Kumar , Krug Elaine , Cromwell Ian , Pappolla Miguel A , Vasu Chenthamarakshan , Lahiri Debomoy K. , Greig Nigel H , Padmaraju Vasudevaraju 
Published: June 2023

AbstractBackgroundHigh serum homocysteine is a risk factor for Alzheimer’s Disease (AD). It has been reported to influence the accumulation of its characteristic lesions ‐ senile plaques (SP) and neurofibrillary tangles (NFT) ‐ containing amyloid β protein (Abeta) and microtubule‐associated protein Tau (MAPT), respectively. Reduced food or calorie intake or branched‐chain amino acids are reported to benefit AD model mice. Restriction of Methionine (Met), an essential amino acid, contributes to increased longevity without calorie restriction.MethodWe treated APP/PS1 transgenic mice with a 75% Met restricted (MR) diet and compared it to an isocaloric isonitrogenous complete diet (CD) for up to 12 months. We subsequently evaluated amyloid loads by ELISA and other APP metabolites by western blotting as described previously (Barnwell et al., 2014, Teich et al., 2018). We collected fecal matter from the colon, extracted DNA, and evaluated the gut microbiome.ResultOur data show that MR treatment substantially lowered brain soluble Abeta at 3 and 6 months. Abeta levels are excessively and presumably saturated in older mice, accounting for the lack of statistically significant differences between the different diets evaluated after twelve months. Nevertheless, older mice showed substantial improvement in behavior in a novel object recognition task after MR treatment. MR treatment is known to be senolytic, and therefore, we are currently examining related processes, such as preservation of lysosomal capacity changes in metabolome, mRNA, and miRNA profiles. Future work involves evaluating methionine and branch‐chain amino acid restriction in AD animal models, such as in human tau‐overexpressing Tg mice, and evaluating miRNAs.MR diets significantly alter gut microbiota. As expected, the bacteria that metabolize Met and Cys were decreased. Specifically, several major species of bacteria were reduced, and the overall diversity of microbiota was increased. Senolysis and improvements in AD pathology may also be mediated by reduced inflammation due to the increased diversification of the microbiome. Thus, such diets may play an important role in strategies to prevent AD, retinal degeneration, and other age‐associated disorders.ConclusionSulfur amino acid restriction reduces amyloid production and preserves cognitive function in mice. Reduced protein diets may be useful in preventing proteinopathies that lead to neurodegeneration.