bluuebunny/crossref_metadata_2025_split huggingface dataset:
Informant‐based report of cognitive decline correlates with age‐adjusted hippocampal volume in mild cognitive impairment and Alzheimer's dementia?
Authors: Sabbagh Marwan Noel , Miller Justin , Wint Dylan 
Published: December 2020

AbstractBackgroundInformant‐based measures can be effective screening tools for cognitive impairment. The Alzheimer’s Questionnaire (AQ; Sabbagh et al., 2010) is a subjective, informant‐based measure that captures five cognitive domains associated with Alzheimer’s disease (AD). The AQ detects amnestic mild cognitive impairment (aMCI) and Alzheimer‐type dementia with high sensitivity and specificity, and has also been shown to predict amyloid burden. We hypothesize that a higher AQ score (greater functional impairment) correlates with lower hippocampal volumes.MethodRetrospective chart review of 131 clinically referred patients with clinical diagnoses of aMCI or mild dementia due to AD was conducted. Diagnostic status (clinical diagnosis made by a neurologist), NeuroQuant measured MRI brain with percentile rank hippocampal volume, Montreal Cognitive Assessment (MoCA) total, AQ‐Total score, and demographic variables were extracted from medical records. Spearman correlation was used to assess the relationship between hippocampal volume and AQ‐Total. As the AQ was used as a factor in assigning diagnostic status, thus the relationship between the AQ and diagnostic status was excluded from analyses.ResultThe analyzed sample was 53% female with a mean of 73.96±10.48 years of age and 14.74±3.51 years of education. Sample means for the MoCA and AQ score were 22.16±4.39 and 10.62±5.29, respectively. Correlation between AQ score and HC volume (as reported as percentile) revealed an inverse relationship, such that higher AQ scores were associated with smaller hippocampal volumes (r =‐0.40 (95% CI ‐0.54 to ‐0.24), p<0.0001).ConclusionIn a mixed‐clinical sample of patients presenting to an outpatient memory disorders center, higher endorsements of functional impairments by caregivers were significantly associated with smaller hippocampal volumes. When used in conjunction with other available measures, these findings further support the role of the AQ in clinical decision‐making, and demonstrate an additional relationship with established AD biomarker outcomes with volumetric MRI.
The peripheral hearing and central auditory processing skills of individuals with subjective memory complaints
Authors: Jayakody Dona M.P. , Sohrabi Hamid , Martins Ralph N. 
Published: December 2020

AbstractBackgroundWith no cure or effective treatment currently in sight, it is critical to identify those factors that may prevent or delay cognitive decline and dementia in older adults, it is important to focus on potentially modifiable risk factors. Untreated hearing loss contributes up to about 9% of the modifiable risk factors in mid‐life (Livingston et al., 2017).MethodA total of 95 participants were recruited from the larger Western Australia Memory Study and were classified as SMCs (N = 61; 20 males and 41 females, mean age 71.47 + 7.19 years) and non‐SMCs (N = 34; 10 males, 24 females, mean age 68.85 + 7.70 years). All participants completed a peripheral hearing assessment, a CAP assessment battery (Dichotic Digits, Duration Pattern Test, Dichotic Sentence Identification, Synthetic Sentence Identification with Ipsilateral Competing Message and the Quick‐Speech‐in‐Noise) and a cognitive screening assessment.ResultThe SMCs group performed significantly poorer than the control group on Synthetic Sentence Identification with Ipsilateral Competing Message ‐10dB and ‐20 dB Signal to Noise Ratio conditions. No significant differences were found between the two groups on the peripheral hearing threshold measurements.ConclusionThe results suggest that individuals with SMCs perform poorly in CAP assessments in comparison to the controls. The poor CAP in SMC individuals may result in a greater cost to their finite pool of cognitive resources. The CAP results provide yet another biomarker that supports the hypothesis that SMCs may be a primary indication on neuropathological changes in the brain affecting various functions. Longitudinal follow up of individuals with SMCs and decreased CAP abilities should inform whether this group is at higher risk of developing dementia as compared to non‐SMCs and to those SMC individuals without CAP difficulties.
Cognitive impairment and disability after arterial stroke in older adults: A hospital‐based study
Authors: Mukku Shiva Shanker Reddy , PT Sivakumar , Kukarini Girish Baburao , Prasad Krishna 
Published: December 2020

AbstractBackgroundStroke and cognitive impairment often co‐exist in older adults. Every one minute three people get stroke in India, who are potentially at risk for cognitive impairment. However the literature on this area is limited from India.The objective is study the cognitive impairment in older adults with arterial stroke. To study the relation between the cognitive impairment and disability.MethodSample includes patients above the age of 45 years with arterial stroke seeking treatment from NIMHANS outpatient departments. Ethical clearance was obtained. Patient underwent neurological examination. Standard instruments applied were Modified Rankin scale (MRS), Barthel index (BI), Stroke specific quality of life (SS‐QOL) and Addenbrooke’s cognitive examination (ACE‐III).Results100 stroke patients were recruited as per the inclusion criteria. The sample included 75% males (M:F‐ 3:1), with mean age of 63.98 (SD‐8.45) years. Among them majority were living with spouse (87%), from urban background (75%) and 52% had education of high school and above. Median duration of stroke at assessment was 5 months. The mean score on MRS, BI and SS‐QOL were 2.12 (SD‐1.13), 82.0 (18.64) and 180 (SD‐35.175)respectively. Among our patients 10% meets criteria for vascular dementia and 20% for mild cognitive impairment.On ACE‐III the mean score was 65.50 (SD‐17.72) with score on Attention‐13.21 (SD‐4.54), Memory‐15.11 (SD‐7.07), Fluency‐5.63 (SD‐3.174), Language‐19.92 (SD‐5.59),Visuo‐spatial‐9.69 (SD‐4.51). There was positive correlation between ACE‐ III scores and Barthel index (r= 0.526; p<0.001)and SS‐QOL (r=0.716; P<0.001).There was negative correlation between ACE‐III score and MRS (r= ‐ 0.599; p<0.001).ConclusionIn our study, one‐third of sample had cognitive impairment, at 5 months (median) after stroke.The prevalence of post stroke cognitive impairment is on the lower side as compared to recent meta‐analysis (Barbay et al., 2018; Merriman et al., 2019) which could be due to inclusion of outpatient sample and time of assessment. Cognitive impairment has negative impact of functioning and quality of life in stroke patients which is in agreement with previous studies.
Neuropathological characteristics associated with a recently identified rare PSEN1 deletion mutation (F175del)
Authors: Vöglein Jonathan , Arzberger Thomas , Willem Michael , Trambauer Johannes , Dieterich Marianne , Biskup Saskia , Guidici Camilla , Brendel Matthias , Roeber Sigrun , Danek Adrian , Steiner Harald , Herms Jochen , Haass Christian , Levin Johannes 
Published: December 2020

AbstractBackgroundThe novel PSEN1single amino acid deletion mutation F175del causes autosomal dominant Alzheimer disease (ADAD) in the late thirties. In vitroF175del features an unusual pattern of APP fragments including an increased production of Aβ39. This Aβ species was found particularly in brain vessels and therefore may contribute to the development of cerebral amyloid angiopathy (CAA).MethodNeuropathological examination was performed in a patient with ADAD caused by PSEN1F175del who died at the age of 45 years. Clinical, neuropsychological, genetic and biomarker findings in this patient as well effects of the PSEN1deletion mutation on Aβ processing were described before (Vöglein et al, Neurobiology of Aging, 2019).ResultCopious cored/compact and diffuse Aβ plaques were found in the cerebral cortex. Interestingly, there were plentiful streaky and several cored/compact and diffuse Aβ plaques also in the cerebellum. A large number of cortical neuropil threads and neurons with fibrillary cytoplasmatic tau aggregates as well as several neuritic plaques were detected (ABC score: A3/B3/C3). CAA with Aβ depositions in the leptomeningeal and cortical vessel walls was detected (Thal phase 2). Furthermore, several Lewy bodies and Lewy neurites were found in the cerebral cortex (Braak stage 6).ConclusionThe neuropathological hallmarks of AD, Aβ plaques and neurofibrillary degeneration, were present in PSEN1 F175del associated ADAD. CAA was found that could be in causal connection with the enhanced Aβ 39 generation caused by the mutation as shown in cell culture. Further, an unusually high cerebellar Aβ burden was detected. In summary, we provide neuropathological characteristics of ADAD caused by PSEN1 F175del and potentially unveiled an effect of an altered Aβ processing that was shown in vitro on brain pathology.
Subtle differences in the appearance of hippocampal layers differentiate preclinical AD from healthy aging
Authors: Xie Long , Das Sandhitsu R. , Wisse Laura , Ittyerah Ranjit , Vergnet Nicolas , de Flores Robin , Wolk David A. , Yushkevich Paul A. 
Published: December 2020

AbstractBackgroundDegeneration of the stratum radiatum lacunosum moleculare (SRLM), located between the cornu ammonis (CA)/subiculum and dentate gyrus (DG) subfields of the hippocampus (Figure 1) and containing apical dendrites of CA pyramidal cells, may be an early feature of AD and can be observed in postmortem studies (Adler et al, 2018). The pathological change in SRLM may produce subtle alteration of image signal on high‐resolution in vivo MRI. We hypothesize that convolutional neural networks (CNNs) can detect such alterations in preclinical AD, yielding a more sensitive biomarker than conventional morphological measurements.MethodsCross‐sectional 0.4x0.4x2.0mm3 T2‐weighted MRI of 285 cognitively normal controls from ADNI were included. The dataset was dichotomized according to amyloid‐ß (Aß) status (+ or ‐) based on PET and divided into training (48%), validation (12%) and test sets (40%, Table 1). Volumes of medial temporal lobe subregions (CA1‐3, DG, subiculum, entorhinal cortex, Brodmann areas 35/36, parahippocampal cortex) were extracted automatically using ASHS (Yushkevich et al., 2015). Small image patches (∼6x6x6 mm3) centered on the SRLM were extracted. A CNN was trained to discriminate patches as Aß+ or Aß‐. The output of the last CNN layer was averaged over all SRLM patches to generate a CNN‐based score for each subject in the test set. ANCOVA with age, sex, education and intracranial volume as covariates was used to test for significance.ResultsWe observed a significant difference in CNN score between Ab+ and Ab‐ controls in the test set (Table 2). None of the conventional volume measures show statistical significance except a trend level effect in parahippcampal cortex opposite the expected result (greater atrophy in Aß+).ConclusionsIn this proof‐of‐concept study, we demonstrated that our novel CNN‐based score is more sensitive to Aß status than standard medial temporal lobe volume measurements. Since the image patches only cover a small area around the SRLM, the score may reflect subtle change of the SRLM in preclinical AD. Better understanding the linkage of SRLM appearance and underlying pathology is required and will be investigated in future work using a dataset of antemortem and postmortem imaging in the same subjects.
Health‐related quality of life of people with dementia and their caregivers
Authors: Zoi Panagiota , Ntanasi Eva , Kalligerou Faidra , Sakka Paraskevi , Gouva Mary 
Published: December 2020

AbstractBackgroundOver the last decades dementia has been a major public health challenge. Caregivers burden is increasing as the disease progresses and the behavior of the person who suffers from dementia is worsening. Caregivers burden has psychological, physical and financial dimensions.The purpose of this research was to measure Health‐Related Quality of Life (HRQoL) of people with dementia and their caregivers and to investigate which parameters have an impact on caregivers burden (Zarit Burden Interview ‐ ZBI). Additionally we investigated existing differences between the estimation of health status by people with dementia, their caregivers for themselves and caregivers assessing their relatives’ condition, using the EQ‐5D‐5L questionnaire. The EQ VAS scale was used as a quantitative measure of health status of participants, both patients and caregivers.MethodThe research was conducted between December 2018 and January 2019 in the Athens Alzheimer Association Day Care Centers. The sample consisted of 200 people (100 people with dementia and their 100 caregivers). Demographic characteristics were recorded for all. People with dementia underwent neuropsychological assessment including MMSE, ACE‐R, GDS, EQ‐5D‐5LResultThe majority of caregivers were women (70%), caring for their parents (50%) and spouses (42%). In our research 36% caregivers had moderate to severe burden (41,9 score’s ZBI). Through the EQ VAS, patients self‐assessed their health at an average of 72.9 points while caregivers rated health for their relatives at an average of 59.19 points.ConclusionOur findings suggest that caregivers health status correlates negatively to the amount of burden as expressed by ZBI scores. High ZBI scores rated by the caregivers also result in low HRQoL
Weight loss predicts Alzheimer’s disease biomarker positivity in cognitively unimpaired middle‐aged adults
Authors: Grau‐Rivera Oriol , Navalpotro Irene , Sánchez‐Benavides Gonzalo , Suárez‐Calvet Marc , Milà‐Alomà Marta , Arenaza‐Urquijo Eider M , Salvadó Gemma , Sala‐Vila Aleix , Crous‐Bou Marta , González‐de‐Echávarri José Maria , Minguillón Carolina , Farrar Gill , Buckley Chris J , Niñerola‐Baizán Aida , Perissinotti Andrés , Simon Maryline , Kollmorgen Gwendlyn , Eichenlaub Udo , Zetterberg Henrik , Blennow Kaj , Gispert Juan Domingo , Molinuevo Jose Luis ,   ALFA Study
Published: December 2020

AbstractBackgroundWeight loss is common in Alzheimer’s disease (AD) and may start before cognitive impairment, but little is known about the relationship between weight change and AD biomarkers in the preclinical Alzheimer’s continuum. We aimed to assess the association between weight change and AD biomarkers and cognitive performance in cognitively unimpaired (CU) adults from the ALFA+ study.MethodWe analyzed data from 295 CU middle‐aged adults with two consecutive (mean interval 3.7 years) weight measures and neuropsychological assessments (n=267). Preclinical Alzheimer's Cognitive Composite (PACC) was computed as an average of z‐scores of episodic memory, semantic fluency and processing speed measures. We measured cerebrospinal fluid (CSF) levels of Aβ42, Aβ40, p‐tau, t‐tau, neurofilament light (NfL) and neurogranin using the Roche NeuroToolKit and Elecsys® immunoassays (n=280), and performed a [18F]flutemetamol PET scan in the follow‐up visit (n=252). PET results were dichotomized (Aβ positive or negative) based on visual read. Using established CSF cutoffs, we grouped participants in three biomarker categories: A‐T‐ (both Aβ and tau negative), A+T‐ (Aβ positive only) and A+T+ (both Aβ and tau positive). Linear and logistic regression and Kernel‐weighted local polynomial smoothing were used for analyses, which were adjusted by age, sex, body mass index, APOE genotype and years of education, as appropriate.ResultWeight loss predicted amyloid PET positivity (odds ratio 1.1, p=0.028) and was associated with significantly higher CSF levels of p‐tau (p=0.005), t‐tau (p=0.005) and neurogranin (p=0.002) (Table 1). Weight loss ≥5% (a standard cutoff for clinically relevant weight change) yielded 87% specificity and 30% sensitivity for amyloid PET positivity. Participants from the A+T+ group experienced significantly higher weight loss compared to A+T‐ (p=0.0029) and A‐T‐ (p=0.0005) groups (Figure 1). Weight loss was not associated with longitudinal changes in cognitive performance and preceded cognitive decline when using Aβ42/40 as a proxy of AD change progression (Table 1, Figure 2).ConclusionWeight loss predicts amyloid PET positivity in CU middle‐aged adults. Our results suggest that weight loss is mainly related with changes in tau‐related and synaptic dysfunction biomarkers and may precede cognitive decline in the preclinical stage of the Alzheimer’s continuum.
Disruptors of the Hsp90/Aha1 complex that reduce tau aggregation
Authors: Keegan Bradley M , Koren John , Blagg Brian S.J. ,   Warren Family Research Center for Drug Discovery and Development
Published: December 2020

AbstractBackgroundAberrant aggregation of misfolded microtubule‐associated protein tau (MAPT, tau) is a hallmark of Alzheimer’s disease (AD) and other neurodegenerative tauopathies. Recently, the ATP‐dependent molecular chaperone family has been identified as a critical mediator of the pathogenic accumulation of misfolded tau. In particular, studies have demonstrated that inhibiting the ATPase activity of Hsp90 reduces pathological tau accumulation and promotes the clearance of tau via the proteosome.MethodThe ATPase activity of Hsp90 is regulated through interactions with a number of co‐chaperones, which direct specific proteins for interaction with Hsp90. Our team recently discovered that one of these co‐chaperones, Aha1 (AHSA1), dramatically increases the production of aggregated tau in vitro (ThT fluorescence assays) and in vivo (transgenic rTg4510 tau mice).ResultWe identified several small molecules that disrupt Aha1/Hsp90 interactions in vitro and demonstrated that one of these compounds, KU‐177, ablates Aha1‐driven enhancement of Hsp90‐dependent tau aggregation.ConclusionUsing KU‐177 as a parent compound, we are developing small molecule disruptors of the Aha1/Hsp90 complex for the treatment of Alzheimer’s disease and have developed assays to evaluate their efficacy.
Daytime napping trajectory over time and its association with cognitive aging: A 13‐year community‐based longitudinal study of older adults
Authors: Li Peng , Gao Lei , Gaba Arlen , Yu Lei , Yaffe Kristine , Buchman Aron S , Bennett David A , Hu Kun , Leng Yue 
Published: December 2020

AbstractBackgroundDaytime napping is common in elderly adults and has been associated with cognitive impairment. Prior studies have assessed napping at one time point, making it difficult to examine the longitudinal progression of napping and its association with cognitive aging. We examined objectively measured daytime napping longitudinally across different stages of Alzheimer’s disease (AD): from no cognitive impairment (NCI), to mild cognitive impairment (MCI), and to Alzheimer’s dementia.MethodWe studied 1,066 participants (female: 810 [76%]; age: 81.0±7.3 [SD]) in the Rush Memory and Aging Project who have been followed for up to 13 years. Motor activities of up to 10 days were recorded annually with actigraphy and used to assess napping objectively. We defined daytime napping episodes as segments between 10AM and 7PM with continuous zero‐activity for ≥10min but <1h (to avoid off‐wrist periods). Segments that were <5min apart were merged. Cognitive and clinical evaluations were administered annually to render a clinical diagnostic classification of NCI, MCI, or AD. To examine how change in napping duration and frequency was associated with progression of AD, we performed linear mixed‐effects models with 2 change points anchored at the diagnoses of MCI and AD while adjusted for age, sex, and education.ResultAt baseline, participants had 1.44±0.04 (mean±standard error) naps with an accumulated duration of 35.0±1.1 min per day. Napping duration increased by 5.2±0.3 min and frequency increased by 0.21±0.01 times every year (both p<0.0001). Compared to those who remained NCI, the rate of increase was more than doubled after MCI diagnosis with an annual increase of 11.4±0.7 min in duration and 0.40±0.02 times in frequency (both p<0.0001); these were doubled further after AD diagnosis with an annual change of 26.3±3.1 min in duration and 0.84±0.08 times in frequency (both p<0.0001).ConclusionDaytime napping duration and frequency increase with aging, and the increase was accelerated with AD progression.
Harmonization of amyloid PET scans minimizes the impact of reconstruction parameters on centiloid values
Authors: Shekari Mahnaz , Niñerola‐Baizán Aida , Salvadó Gemma , Battle Mark R , Buckley Christopher , Farrar Gill , Operto Greg , Falcon Carles , Arenaza‐Urquijo Eider M , Perissinotti Andrés , Molinuevo Jose Luis , Gispert Juan Domingo ,   ALFA study
Published: December 2020

AbstractBackgroundThe Centiloid method has been proposed to enhance the comparability of amyloid PET quantification across different amyloid tracers and to provide a reference metric. In this study, we first quantified the impact of reconstruction parameters on Centiloid values for different reference regions, then we evaluated the reduction of this source of bias after PET image harmonization.MethodA total of 71 cognitively unimpaired participants from ALFA+ cohort were included in this study. For each participant a 18F‐flutemetamol PET scan and a T1‐weighted MRI scan were acquired. A Hoffman 3D‐brain phantom filled with 0.5 mCi of 18F‐FDG was scanned in the same tomograph. Participant and phantom PET data were reconstructed with 4 different protocols used in the clinical and research settings (Table1). The reconstruction with the coarsest spatial resolution was selected as the reference. The remaining 3 were harmonized to yield the same effective spatial resolution using the protocol used in the ADNI study. All images were quantified with a validated Centiloid pipeline using an AAL composite and different reference regions (Whole Cerebellum, Cerebellar Gray, Pons and White Matter). The mean absolute difference in Centiloids (CL) between different reconstructions of the same scan was calculated using the coarsest resolution as reference. Differences below 2.5 CL were considered to be irrelevant based on published test‐retest data.ResultRespectively, Figures 1 and 2 show the Hoffman phantom and the amyloid PET scans before and after harmonization. While mean absolute differences were below the test‐retest threshold for the Cerebellar Gray and whole cerebellum, differences up to 9 CL were observed for the Pons (Table2). White matter as reference region showed the biggest sensitivity to reconstruction parameters and the bias was dependent on the amyloid load (Figure 3c). After harmonization differences were always below the test‐retest threshold.ConclusionReconstruction parameters impact the Centiloid values as a function of reference region. While the impact using Cerebellar gray and the Whole Cerebellum was minor, important differences were observed when using the pons and white matter as reference regions. In all cases, harmonization of the effective spatial resolution was able to bring these biases below the test‐retest threshold.