bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between cerebral amyloid angiopathy and plasma homocysteine levels in Alzheimer’s disease
Authors: Kanemaru Kazutomi , Kanemaru Akiko , Murayama Shigeo 
Published: December 2020

AbstractBackgroundCerebral amyloid angiopathy (CAA) is the characteristic vascular pathology in Alzheimer’s disease (AD). The vascular changes including CAA contribute to mental decline in AD. Elevated plasma total homocysteine (tHcy) is reported to be an independent risk factor for Alzheimer’s disease (AD). Elevated tHcy is also reported to result in CAA in mice. Here we investigated the relationship between CAA and plasma tHcy levels in AD.MethodThe subjects of this study consisted of clinically diagnosed 136 patients with AD (83 females, 53 males, age 75.2±8.8 years). The cortical microbleeds shown by T2*‐weighted MRI images could be CAA‐related. We divided the AD patients into two groups; CAA(+) (AD with CAA, n=46) and CAA(‐) (AD without CAA, n=90). We compared the levels of plasma tHcy between the two groups: CAA(+) and CAA(‐). We also compared CSF biomarkers (tau, ptau‐181 and Abeta42) and MMSE scores between the two groups. The CSF samples were obtained by lumbar puncture after informed consent was obtained. The CSF levels of tau, ptau‐181 and Abeta42 were measured by ELISA (Fujirebio, Belgium) according to the manufacturer’s protocol.ResultThe tHcy levels were 14.3±10.5 nmol/ml in the CAA(+) group and 11.6±4.0 in the CAA(‐) group. The tHct levels showed no significant difference between the two groups. The CSF Abeta42 levels were significantly lower in the CAA(+) group (274.2±108.7 pg/ml) than those in the CAA(‐) group (316.8±112.1 pg/ml, p<0.05, t‐test), whereas the CSF tau and ptau levels showed no difference between the two groups. MMSE scores were lower in the CAA(+) group (16.5±7.0) than those in the CAA(‐) group (20.3±6.3) (p<0.005, t‐test). The tHcy levels were not related to any of CSF biomarkers (tau, ptau‐181 or Abeta42) .ConclusionPlasma tHct levels showed no significant difference between the two groups: CAA(+) and CAA(‐).CSF levels of Abeta42 and MMSE scores were lower in the CAA(+) group than those in the CAA(‐) group.
Polygenic risk score for Alzheimer’s disease is related to amyloid positivity in subjective cognitive decline: The SCIENCe project
Authors: van der Lee Sven J. , Ebenau Jarith L. , Jansen Iris E. , Verberk Inge M.W. , Scheltens Philip , Teunissen Charlotte E. , Barkhof Frederik , Reinders Marcel J.T. , Van Berckel Bart N.M. , Holstege Henne , van Der Flier Wiesje 
Published: December 2020

AbstractBackgroundThe majority of individuals with subjective cognitive decline (SCD) is worried well, but in some the subjective experience of cognitive decline herald’s incipient neurodegenerative disease. Understanding the determinants of disease in SCD is important to separate wheat from chaff. Here we studied APOE and a polygenic risk score for Alzheimer’s disease (AD) in a cohort of SCD that was classified according to the ATN‐framework.MethodWe classified 542 participants with SCD (59.2±8.7 years, 38.9%Female, MMSE 28.3±1.5) from the Amsterdam Dementia Cohort and SCIENCe project according to the ATN‐framework, as determined by amyloid PET or CSF Abeta(A), CSF p‐tau(T) and MRI‐based medial temporal lobe atrophy(N). We reduced the number of categories to three: controls (A‐T‐N‐ or normal AD biomarkers, N=310(57%)), non‐AD pathologic change (A‐T‐N+, A‐T+N‐, A‐T+N+, N=142 (26%)) and the Alzheimer’s continuum (A+T‐N‐, A+T‐N+, A+T+N‐, A+T+N+, N=90(17%)). We determined APOE ɛ4 and 39 other genetic variants that were associated in previous studies with AD using array genotyping or imputation. A weighted AD polygenic risk score (AD‐PRS) was calculated based on 39 variants (excluding APOEɛ4). Logistic regression models were fitted for the associations between AD‐PRS and APOEɛ4 with Alzheimer’s continuum and non‐AD pathological changes. For 324 participants follow‐up for dementia was available (3.1±2.5 year) and progression could be studied. Cox proportional hazard models were used to analyse progression to all‐cause dementia (N=36, 6.6%) and AD‐dementia (N=22, 3.6%). Associations were corrected for 5 ancestry principal components.ResultThe APOE ɛ4 genotype was associated with Alzheimer’s continuum (OR=3.6, 95%CI 2.4‐5.3, P=3.0×10‐10) as well as non‐AD pathologic changes (OR=1.5, 95%CI 1.1‐2.2, P=1.6×10‐2). The AD‐PRS was associated with Alzheimer’s continuum (ORper 1‐SD=1.4, 95%CI 1.1‐1.8, P=3.5×10‐3), but not with non‐AD pathologic changes (OR=1.1, 95%CI 0.9‐1.3, P=0.64). In the progression analysis: APOEɛ4 was associated with all‐cause dementia (HR=1.7, 95%CI 1.1‐2.7, P=2.3×10‐2) as well as AD‐dementia (HR=2.3, 95%CI 1.3‐4.2, P=4.5×10‐3). The AD‐PRS was not associated with progression to all‐cause dementia (HR=0.9, P=0.4) or AD‐dementia (HR=1.4, P=0.13).ConclusionIn individuals with SCD APOE ɛ4 and an AD‐PRS are associated with the presence of amyloid biomarkers (Alzheimer’s continuum), showing that genetic factors can identify individuals at risk in individuals that are cognitively normal.
CSF and FDG‐PET study of the AD continuum: Biochemical and imaging features of two different mechanisms of neurodegeneration
Authors: De Lucia Vincenzo , Bonomi Chiara Giuseppina , Motta Caterina , Assogna Martina , Scaricamazza Eugenia , Martorana Alessandro , Koch Giacomo 
Published: December 2020

AbstractBackgroundAlzheimer's Disease (AD) is a biological and clinical continuum which diagnosis necessarily passes through the analysis of CSF and/or imaging biomarkers. Presence of amyloidosis introduces the concept of AD continuum while the presence of either CSF tau pathology or 18FDG‐PET imaging introduce to the concept of neurodegeneration. However isolated amyloidosis, which is part of the AD continuum often presents with positive 18FDG‐PET although CSF tau levels remain within the range. Here we aimed to investigate the neuropsychological, CSF and 18FDG PET biomarkers of the AD continuum in order to better understand the usefulness of the NIA‐A criteria in terms of diagnosis and prognosis of the disease.MethodWe evaluated 101 patients suffering from amnestic and mild cognitive impairment from March 2018 to January 2019 in our Memory Clinic at the Policlinico Tor Vergata, Rome. Patients underwent neuropsychological assessment, ApoE genotyping, 18FDG PET and lumbar puncture to evaluate CSF biomarkers (Aβ‐42, t‐Tau, p‐Tau) for diagnostic purposes. We classified all patients following the NIA‐A criteria.ResultIndividuals with AD continuum despite the absence of tau pathology in CSF show images of neurodegeneration. Their pattern remain however different from those suffering from AD, having reduced or even absent involvement of the frontal lobes in 18FDG PET studies. Similar results were not obtained in neuropsychological assessment . Frontal lobe hypometabolism and executive function impairment in A+T+ subjects were associated with CSF t‐Tau and p‐Tau increase. 18FDG PET neurodegeneration and Tau degeneration refers to different mechanisms of cell damage, whereas CSF lactate doesn’t correlate with 18FDG PET hypometabolism.ConclusionAD continuum is characterized by different pattern of CSF and imaging biomarkers. Neurodegenerative mechanisms related to amyloidosis differ qualitatively and quantitatively from those associated to tau pathology and the presence or the absence of ε4 polymorphism. These features represent an important step forward in our understanding of AD pathophysiology.
Audiovisual integration improves task performance in AD and bvFTD
Authors: McLoughlin Bethany , Benhamou Elia , Sivasathiaseelan Harri , Hardy Chris J.D. , Bond Rebecca L. , Russell Lucy L. , Rohrer Jonathan D. , Warren Jason D. , Agustus Jennifer L. 
Published: December 2020

AbstractBackgroundComplex analysis of sensory inputs, such as auditory scene analysis and spatial localisation, is impaired in Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Multisensory integration research demonstrates that synchronous stimulation in one sense (e.g. vision) can modify processing of suboptimal sensory inputs from another sense (e.g. hearing) in the healthy brain. However, the potential benefit of multisensory stimulation to reduce common symptoms in dementia has not been fully examined.MethodPatients living with AD (n = 20) or bvFTD (n = 12), and healthy age‐matched controls (n = 18) were recruited to perform three brief cognitive tasks: 1. Cocktail party effect, identify a name spoken in a noisy environment; 2. Spatial ventriloquism, discriminate the location of an auditory stimulus (left/right of centre); and 3. Detect a suboptimal visual stimulus. Task performance was compared between unisensory, audiovisual congruent, and audiovisual incongruent conditions, and between groups.Result1. Identification of spoken names in a noisy auditory environment was significantly worse for both patient groups than controls. All groups performed significantly better when viewing an accompanying video of congruent lip movements. The AD group showed some improvement for incongruent videos that cued the onset of the spoken name. 2. Auditory spatial discrimination was significantly worse in the AD group than controls, but both groups were significantly biased by the locations of the accompanying visual stimulus. The bvFTD group was only influenced by spatially incongruent visual stimulation. 3. Detection of a near‐threshold peripheral visual stimulus was improved by a synchronous auditory stimulus, irrespective of spatial congruency, in the bvFTD and control groups. In the AD group, only spatially congruent or neutral auditory stimuli benefitted visual stimulus detection.ConclusionCongruent audiovisual stimulation improves the ability of people living with AD or bvFTD to understand voices in a noisy environment, locate auditory sounds, and detect unreliable visual events. Congruency of audiovisual stimulation in different domains (e.g. semantic, spatial) provides evidence for disease‐specific stratification of multisensory integration profiles. As such, multisensory integration provides a mechanism to improve reliability of sensory inputs and the potential to alleviate symptoms in daily life if tailored according to disease.
Spanish translation and cultural adaptation of the memory support system: A pilot study
Authors: Santos Octavio A , Espinoza Dairlin , Pedraza Otto , Chandler Melanie 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) affects 1 in 9 Hispanics aged ≥45 in the U.S., including 1 in 3 who report that SCD interferes with instrumental activities of daily living (IADLs) and 1 in 2 who give up IADLs or need help performing household tasks. A curriculum and calendar/note‐taking system [Memory Support System (MSS)] has proven effective to sustain independence in IADLs in patients with mild cognitive impairment, and protect mood among program partners compared to controls. Until recently, the MSS had only been utilized among English‐speaking, predominately Caucasian, samples.MethodThis study investigated the use of a translated and culturally‐adapted MSS in 20 Spanish‐speaking participants with SCD [80% female, age M = 66.8 (SD = 10.3), education M = 14.8 (SD = 3.6)] and their program partners. A within‐subject multiple baseline design in a 10‐session, 2 to 6‐week MSS training schedule was utilized. Outcome measures included treatment adherence and self‐ and informant‐report questionnaires of IADLs, anxiety, depression, self‐efficacy, caregiver burden, and quality of life.ResultMSS training significantly improved adherence to the MSS calendar by treatment completion (d = ‐3.75). Participants with SCD also showed significant improvement in overall functional status (d = 0.72), and in daily activities requiring organizational skills (d = 0.66). Symptoms of depression (d = 0.99) and anxiety (d = 0.84) also improved by treatment end, and program partners reported significant improvement in their own anxiety (d = 0.84). There was a significant association between MSS adherence and anxiety in participants with SCD (r = ‐.51).ConclusionOverall, preliminary findings suggest that with appropriate training, Spanish‐speaking participants with SCD can and will use a memory notebook system to help compensate in daily life for their SCD and decrease emotional distress. Future research should investigate the Spanish MSS efficacy over time in a randomized controlled trial.
Differences in lifestyle factors based on latent class analysis cognitive profiles in non‐demented older adults
Authors: Boots Elizabeth A , Drabick Deborah AG , Delano‐Wood Lisa , Bondi Mark W , Libon David J , Lamar Melissa 
Published: December 2020

AbstractBackgroundModifiable lifestyle factors such as diet and physical activity are associated with cognitive function in aging adults. However, less is known regarding the intersection between lifestyle factors and cognitive heterogeneity in this same population. Understanding the types of dietary and physical activity patterns that are associated with differing cognitive profiles in normal aging could provide clinically meaningful data to promote cognitive health. Therefore, we characterized cognitive subgroups within a community‐dwelling sample of non‐demented, non‐depressed older adults and examined whether resulting cognitive subgroups differed on dietary and physical activity measures.Method121 non‐demented, non‐depressed participants (M age=67.69; 49.6% female; 60% minority; MMSE=28.62) completed a neuropsychological evaluation. Latent Class Analysis (LCA) utilizing six cognitive scores (CVLT Delayed Free Recall & Recognition Discriminability, ‘Animal’ and Letter Fluency, Letter‐Number Sequencing, & Boston Naming) revealed 4 cognitive subgroups with 1) high‐normal cognition (50.4%); 2) normal cognition (25.6%); 3) poor memory (15.7%); and 4) poor executive functioning (8.3%). A subset of participants completed the Sedentary Behavior Questionnaire and CHAMPS Physical Activity Questionnaire for Older Adults (n=96), and the Food Frequency Questionnaire (n=89). Weekly sedentary behavior and weekly moderate‐to‐vigorous physical activity (MVPA) total scores and a FFQ‐derived Mediterranean Diet (MedDiet) score were calculated according to published criteria. Differences between the four cognitive subgroups and these lifestyle variables were examined using ANCOVA adjusting for age, sex, race, word reading, depressive symptoms, and body mass index.ResultThere was a significant difference between cognitive subgroups (p=.016) for MedDiet consumption. Post‐hoc analyses revealed participants with high‐normal cognition had higher MedDiet scores than those with normal cognition (p=.001). There were no significant differences between cognitive subgroups for sedentary behavior (p=.695) or MVPA (p=.731) scores.ConclusionLCA‐defined cognitive subgroups within non‐demented, non‐depressed older adults showed group differences in MedDiet consumption (participants with high‐normal cognition greater than those with normal cognition). No group differences were seen with sedentary behavior or physical activity. When choosing ‘one thing’ to advise non‐demented, non‐depressed older adults about maintaining cognitive health, adherence to a MedDiet may mean the difference between good, better, and best cognitive aging.
Diagnostic accuracy of the 10/66 dementia assessment tool in Māori, Fijian‐Indian, Samoan and Tongan elders with memory problems living in South Auckland, New Zealand
Authors: Martinez‐Ruiz Adrian , Yates Susan , Cheung Gary , Dudley Makarena Diana , Krishnamurthi Rita , Fa'alau Fuafiva , Roberts Mary , Taufa Seini , Fa'alili Jacinta , Kerse Ngaire , Cullum Sarah 
Published: December 2020

AbstractBackgroundNew Zealand is a multicultural multilingual country which brings challenges if we aim to conduct a dementia prevalence study that is representative of the whole of NZ population. The 10/66 dementia assessment tool was developed for use in non‐English speaking communities in order to accurately measure the prevalence of dementia. It is a language‐fair, culture‐fair questionnaire used in epidemiological studies of dementia. It has been translated and adapted into a culturally fair instrument for use with Māori, Fijian‐Indian, Samoan and Tongan elders living in New Zealand (NZ).MethodThe translated and adapted 10/66 instrument versions were administered in the selected ethnicities. The results of the 10/66 dementia assessment it´s been tested in older people with and without dementia who have received a “gold standard” assessment in a local memory service in South Auckland. Each ethnic group included 15 subjects with dementia and 15 subjects without dementia.ResultData is still being collected and analysed. The results will be presented at the conference, however the preliminary results for both Māori and Fijian‐Indian communities showed that the 10/66 dementia assessment has a sensitivity and specificity above 85%.ConclusionWe will test a culturally appropriate and scientifically rigorous method to calculate the prevalence of dementia in an inter‐ethnic community that includes Māori, Fijian‐Indian, Samoan and Tongan elders living in NZ. The information from this study can be used by the Ministry of Health to direct relevant resources towards raising awareness, reducing stigma, improving treatment and developing culturally appropriate dementia care services.
Effect of intensive versus standard blood pressure control on cerebral blood flow in SPRINT
Authors: Dolui Sudipto , Detre John A. , Cho Monique E. , Haley William E. , Launer Lenore J. , Punzi Henry A. , Rastogi Anjay , Still Carolyn H. , Weiner Daniel E. , Wright Jackson , Williamson Jeff D. , Wright Clinton B. , Nasrallah Ilya M. 
Published: December 2020

AbstractBackgroundHypertension is a major risk factor for cardiovascular and cerebrovascular disease including stroke, small vessel disease, and dementia. The Systolic blood PRessure INTervention (SPRINT) randomized trial prospectively evaluated the effects of intensive systolic blood pressure (SBP) control (target SBP<120mmHg) versus standard control (SBP<140mmHg) on cardiovascular outcomes in individuals without baseline diabetes or stroke, and included cerebral blood flow (CBF) measurements. Previous studies with much smaller sample sizes and shorter duration suggested stable CBF in response to intensive treatment (SBP<125mmHg) [1], but long term effects are unknown. We evaluated the long‐term effects of intensive blood pressure treatment on CBF.MethodWhole brain CBF was measured at 3T using pseudocontinuous arterial spin labeled (ASL) perfusion MRI at baseline and after 3.9±0.3 years. Total white matter lesion (WML) load was measured from Fluid Attenuated Inversion Recovery T2 MRI. Data from 324 subjects with adequate ASL scan quality acquired from 6 sites were included.ResultDemographics and scanner specific CBF values are provided in Table 1. The intensive treatment group was older (p=0.01), but was otherwise similar to the standard group at baseline. There was a significant effect on the longitudinal CBF change (p=0.006) of the intensive treatment (5.7% increase) compared to the standard treatment (4.0% decrease, Fig 1). Secondary analysis showed a significant increase in age‐adjusted fractional CBF for the intensive treatment group (p<0.001) with no change (p=0.24) in the standard treatment group. Change in CBF was not associated with change in WML.ConclusionSustained intensive antihypertensive treatment does not reduce whole brain CBF, in fact it showed an increase in whole brain CBF relative to standard therapy. While improved CBF might contribute to the reduced WML progression observed in the intensive‐therapy group versus standard therapy in SPRINT[2], we did not observe a direct correlation between CBF changes and WML changes. References: (1) Croall et al. JAMA‐Neurol,2018; (2) Nasrallah et al., JAMA‐Neurol, 2019.
Neural‐cognitive changes across the lifespan: Evidence from reference ability neural network (RANN)
Authors: Argiris Georgette , Stern Yaakov , Habeck Christian 
Published: December 2020

AbstractBackgroundCognitive functions and their underlying neural substrates change across the lifespan (for a review, see Grady et al., 2012). In an attempt to capture these changes, most prior work utilizing a cross‐sectional approach have investigated age‐group differences in behavioral performance or neural activations related to particular functions. In the present study, we aimed to quantify neural changes in the brain associated with four principal cognitive domains by considering age as a continuous factor and linking regions displaying the greatest change in each domain with behavioral performance.MethodWe collected behavioral and fMRI data from 240 cognitively‐healthy community‐dwelling adults between the ages of 21 and 80 on a battery of tests relating to the four domains or “reference abilities” (i.e., Episodic Memory, Fluid Reasoning, Processing Speed, Vocabulary; see Stern et al., 2014). We applied a Gaussian kernel, centered on each year of life in our sample, in order to generate weights that would allow us to construct a brain map for each target age, derived from the weighted activations across all participants (Ericsson et al., 2008). Subsequent subtraction of these maps allowed us to quantify the age‐related differences, ∆=T(age) ‐ T(age+1), in each domain.ResultResults indicated significant differences between successive ages around 40 years of age in two of the four domains: Fluid Reasoning and Processing Speed. Furthermore, for each domain, we selected those voxels for which change was the greatest and performed correlations between voxel activations and behavioral performance. For Episodic Memory, we observed significant positive correlations between behavior and activation namely in the bilateral rolandic operculum, thalamus, right postcentral gyrus, and left supramarginal gyrus, whereas for Processing Speed, we observed significant negative correlations largely in the supplementary motor area, left postcentral gyrus, right precentral gyrus, and cerebellum crus VI.ConclusionThese findings emphasize the utility of analyzing lifespan changes along a continuum and reveal significant differences, suggesting a significant peak change, that is similar across domains.