bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Do Event‐Related Gamma Oscillations Differ in Alzheimer’s Disease From Other Types of Dementia ?
Authors: Güntekin Bahar , Bölükbaş Burcu , Duygun Rümeysa , Kuloğlu Hikmet Buse , Yemeniciler İrem , Yıldırım Ebru , Aktürk Tuba , Yener Görsev 
Published: December 2023

AbstractBackgroundAlthough recent studies showed that gamma frequency entrainment might have therapeutic effects on Alzheimer’s Disease (AD) (Iaccarino et al. 2016), the gamma band abnormalities in AD patients are still poorly understood, while some studies presented increased gamma responses in AD, others showed reduced gamma responses (Güntekin et al., 2022). The differentiation of gamma responses between different dementia types is also not known. The present study aims to analyze the event‐related gamma responses in AD patients and to find out how the event‐related gamma responses differentiate between AD, Parkinson’s disease dementia (PDD), and Lewy Body dementia (DLB).MethodEEG of 17 DLB, 19 PDD, 20 AD patients, and 20 healthy controls was recorded with a 32‐channel EEG device. Subjects had performed visual oddball paradigm during EEG recordings. Event‐related phase locking and Event‐related power were analyzed in three gamma frequency bands (25‐30 Hz, 30‐35 Hz, 35‐48 Hz) in three different time windows (0 200 ms, 200 400 ms, 400‐600 ms) for target and non‐target stimuli. Repeated measures of ANOVA were used with the between‐subjects and within‐subjects factors.ResultTarget responses elicited higher gamma phase locking than the non‐target responses (p<0.05). Healthy subjects had higher gamma phase locking than AD, PDD, and DLB patients (p<0.05). The healthy control group had increased gamma power in the 0‐200 ms time window at frontal and central locations (p<0.05); however, patient groups did not have this early time window increase of gamma responses. Furthermore, although it was non‐significant, gamma phase locking values of PDD and DLB patients were worse than AD.ConclusionThe present study showed that AD, PDD, and DLB patients had reduced event‐related gamma phase locking and power in the early time window compared to healthy elderly controls. The gamma phase locking values of PDD and DLB patients were worse than those of AD patients. The present study showed that similar to AD patients and other dementia types could also have deficits in the gamma frequency band. Since the PDD and DLB patients had even more abnormal gamma band activities, the gamma entrainment could also have positive effects in these groups of patients.
Hemodynamic aspects in the association between orthostatic hypotension and cognition: a prospective cohort study
Authors: Starmans Naomi LP , Wolters Frank J. , Leeuwis Anna E , Bron Esther E , de Bresser Jeroen , La Rocca Hans‐Peter Brunner‐ , Staals Julie , Muller Majon , Biessels Geert Jan , Kappelle Jaap ,   Heart‐Brain Connection Consortium
Published: December 2023

AbstractBackgroundOrthostatic hypotension (OH) is related to an increased risk of dementia. To explore whether cerebral hypoperfusion could play a role in this relation, we assessed different OH patterns in relation to cognitive functioning and vascular brain injury in hemodynamically compromised participants of the Heart‐Brain Connection Study.MethodParticipants with carotid occlusive disease (COD) or heart failure (HF), and reference participants underwent OH measurements, neuropsychological assessment and a brain MRI at baseline and after 2 years of follow‐up. OH was defined as a drop in blood pressure upon standing of ≥ 20 mmHg systolic or ≥ 10 mmHg diastolic. We analyzed the association between OH, global cognitive functioning, white matter hyperintensity volume and lacunar infarcts with linear and logistic regression. We stratified by participant group, severity and duration of OH, chronotropic incompetence and presence of orthostatic symptoms to model different levels of hemodynamic impact.ResultWe included 348 participants (mean age 67.3±8.7 years, 121 females) of whom 192 completed 2‐year follow‐up. OH was present in 118 (33.9%) participants. Overall, prevalence of OH was not associated with cognitive function at baseline, with similar results after stratification by participant group. Still, those with OH did perform worse on cognitive assessment in case of large blood pressure drops (≥25 mmHg systolic or ≥15 mmHg diastolic; β ‐0.07, 95%CI: ‐0.13 – ‐0.02), in case of absent chronotropic incompetence (increase in heart rate ≥8 beats/min; β ‐0.06, 95%CI: ‐0.10 – ‐0.01) or when OH was accompanied by clinical symptoms (β ‐0.10, 95%CI: ‐0.18 – ‐0.01). OH patterns were not associated with change in cognition during follow‐up in the total sample. Brain imaging markers at baseline or follow‐up did not differ between participants with or without OH.ConclusionWhile more severe OH was associated with reduced cognitive function cross‐sectionally, we observed no association with cognitive decline or vascular brain injury on MRI in hemodynamically compromised individuals. These observations do not support the hypothesis that hypoperfusion is the main driver of the association between OH and dementia risk.
Clinical Characteristics and Follow‐up Assessment in Patients Diagnosed with Alzheimer’s Dementia Through Regional Dementia Centers and Conventional Hospital System
Authors: Jeong Eun Hwan , Park Kyung Won , Park Doug Ho 
Published: December 2023

AbstractBackgroundThe rapidly increasing socioeconomic burden due to dementia is a significant global public health issue. To address this issue in Korea, regional dementia centers (RDCs) have been established nationwide. This study investigated the clinical features and courses in patients diagnosed with Alzheimer’s dementia(AD) through RDCs or conventional hospital system in the community.MethodThis retrospective cohort study was performed in a single general hospital and included patients newly diagnosed with AD from January 2019 to March 2022. Analysis was conducted to compare two groups of patients: the hospital group, who came directly to the hospital, and the RDC group, who were referred to the hospital from the RDCs in Pohang city. Their clinical courses were followed for a year after AD diagnosis.ResultA total of 1209 study participants were assigned to the hospital (n = 579) or RDC group (n = 630). The RDC group was 80.1 ± 6.6 years old, significantly older than the hospital group (P <0.001). In the linear regression model, the RDC group independently associated the CDR‐SB increment (β = 19.007 and P <0.001). In the multivariable binary logistic regression model, the RDC group showed a significantly lower risk for hospitalization within one year after the diagnosis of AD (odds ratio, 0.54; 95% confidence interval, 0.30–0.98; P = 0.014).ConclusionAD patients in the RDCs were older, diagnosed with more advanced conditions, and were rated as having more rapid cognitive decline than patients diagnosed in the conventional hospital system. RDCs may contribute to the initiation of treatment by discovering AD patients hidden in the community due to limited access to healthcare.
Domain‐specific subtle cognitive decline associations with cerebrospinal fluid and plasma β‐amyloid and p‐tau Alzheimer’s disease biomarkers in cognitively unimpaired individuals
Authors: López‐Martos David , Sánchez‐Benavides Gonzalo , Suarez‐Calvet Marc , Escalante Armand González , Milà‐Alomà Marta , Gispert Juan Domingo , Minguillón Carolina , Kollmorgen Gwendlyn , Carboni Margherita , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Grau‐Rivera Oriol 
Published: December 2023

AbstractBackgroundPresence of Alzheimer’s disease (AD) core pathology, β‐amyloid (Aβ) and p‐tau, has been proven to impact cognitive function even in cognitively unimpaired (CU) individuals. Although the Aβ and p‐tau (AT) effect has been mainly associated with memory function, recent evidence (Tideman, P., 2022. Neurology) suggested that Aβ levels were associated independently of p‐tau with the cross‐sectional performance in executive functioning. The aim of the present study was to explore specific associations of cerebrospinal fluid (CSF) and plasma Aβ and p‐tau baseline levels with the longitudinal change in several cognitive domains in a sample of CU individuals at increased risk of AD.MethodWe analyzed the associations of baseline CSF Aβ42/40, and p‐tau181 as well as plasma Aβ42/40, and p‐tau231 levels, with domain‐specific cognitive changes 3 years after baseline in 337 CU participants from the ALFA+ study. We defined AT groups (A‐T‐, A+T‐, and A+T+) using CSF levels, and the A‐T‐ group’s baseline performance served as reference to compute z‐scores for Visual Processing, Semantic Fluency, Executive Functioning, Episodic Memory, and Attentional Processing. Delta scores were computed by subtracting baseline from follow‐up scores and then compared among AT groups by means of ANCOVAs. Multiple linear regressions were performed on the whole sample using CSF Aβ42/40, p‐tau181 and plasma Aβ42/40, p‐tau231 as predictors of change in cognitive function.ResultA+T+ individuals showed a significant decline in Executive Function (p = 0.005, Cohen’s d = 0.716), and Attentional Processing (p = 0.032, Cohen’s d = 0.563), but not in Episodic Memory (p = 0.334) when compared with A‐T‐ individuals. In the whole sample, CSF Aβ42/40 was associated independently of p‐tau181 with a decline in Semantic Fluency (β = 6.284, p = 0.013), Attentional Processing (β = 3.828, p = 0.020), and Episodic Memory (β = 3.513, p = 0.004). Plasma p‐tau231 levels were associated with a decline in Semantic Fluency (β = ‐0.413, p = 0.045). CSF p‐tau181 and plasma Aβ42/40 were not associated with cognitive changes.ConclusionExecutive Function and Attentional Processing were more sensitive than Episodic Memory in capturing the early subtle cognitive changes in CU individuals with underlying AD pathology. Attentional Processing was the only cognitive domain associated both with the status of AD biomarkers and with the effect of CSF Aβ levels independently of p‐tau.
Home‐based solutions for dementia management: Results from a survey of dementia caregiver
Authors: Rodriguez Francisca S , Ross Sabrina D , Ziegert Nadja 
Published: December 2023

AbstractBackgroundLiving with dementia affects almost every aspect of life. Medical care concepts, however, focus mainly on biological aspects of the disease so that many caregivers have to find solutions themselves for dealing with the other aspects of daily life. Aim of the present study was to identify such solutions.MethodWe conducted a survey with seven groups of stakeholders in dementia care, (1) caring spouses, (2) caring family members, (3) professional caregivers, (4) volunteering/nonprofessional caregivers, (5) therapists, (6) counselors for people with dementia, and (7) people with dementia themselves. A total of 131 participants reported their experiences and perceptions in structured interviews.ResultWe will report on home‐based solutions for dementia management our participants have reports. Specifically, we report on the type of solutions, by whom they are conducted, how often they are applied, how they are financed, and what positive effects are experienced. Further, we report on what our participants perceived as most effective for increasing well‐being, reducing cognitive decline, and dealing with behavioral problems or with depression.ConclusionOur results indicate a number of useful home‐based solutions for people with dementia. Given the many challenges that come with dementia, care concepts incorporating such solutions are urgently necessary to improve well‐being of those living with dementia.
APOE3 Christchurch heterozygosity delays clinical onset in autosomal dominant Alzheimer’s disease
Authors: Quiroz Yakeel T. , Aguillon David , Zuluaga‐Castaño Yesica , Baena Ana Y. , Vasquez Daniel , Garcia Gloria , Madrigal Lucia , Hincapie Liliana , Sanchez Justin S , Sepulveda‐Falla Diego , Vila‐Castelar Clara , Gomez Liliana Ramirez , Aduen Paula , Acosta‐Uribe Juliana , Kosik Kenneth S. , Johnson Keith A. , Sperling Reisa A. , Reiman Eric M. , Lopera Francisco , Arboleda‐Velasquez Joseph F 
Published: December 2023

AbstractBackgroundWe previously reported a case of a homozygous woman with the APOE3 Christchurch (R136S, APOE3Ch) variant who demonstrated extreme resistance to autosomal dominant Alzheimer’s disease (ADAD) caused by the PSEN1 E280A variant. In this study, we examined the potential protective effects of APOE3Ch against ADAD by characterizing the clinical profile of individuals who were heterozygous for the APOE3Ch variant from the Colombian kindred with the PSEN1 E280A variant.MethodsA total of 421 carriers of the PSEN1 E280A variant were included. Of the 421 carriers, 12 were heterozygous for APOE3Ch (including the previously reported homozygous for APOE3Ch). Clinical and neuropsychological assessments were performed in Spanish at the University of Antioquia in Colombia. Four of the APOE3Ch carriers also donated their brains for postmortem studies. A PSEN1 E280A who is heterozygous for the APOE3Ch variant also underwent structural MRI and amyloid and tau PET imaging.ResultsOur findings showed that PSEN1 E280A carriers who are heterozygous carriers of the APOE3Ch variant had a significantly delayed onset for mild cognitive impairment (MCI, median age of 51 vs. 45 years; p = 0.0048) and dementia (52.5 vs. 48 years; p = 0.016), compared to PSEN1 E280A carriers without the APOE3Ch variant. Specifically, APOE3Ch carriers had seven‐time higher odds of developing MCI and three‐time higher odds of developing dementia at a later age than 75% of all the PSEN1 E280A carriers (odds ratio [OR] = 7.6; 95% confidence interval [CI] 1.9, 29.2, p<0.05); dementia OR = 3.07; 95% CI 1.01, 9.33). Initial characterization of brain imaging of a PSEN1 E280A carrier who is heterozygous for the APOE3Ch variant showed levels of medial temporal lobe tau pathology and hippocampal atrophy that were lower than expected for a typical carrier of their age, and similar to our observations in the previously reported APOE3Ch homozygote case.ConclusionsThese clinical, cognitive, and neuroimaging data provide evidence that APOE3Ch heterozygosity delays the onset of cognitive decline and may have a protective, dose‐dependent effect against tau pathology and neurodegeneration. These results provide support for the potential of the APOE3Ch variant as a target for the development of new treatments for AD.
Cost‐effectiveness of amyloid‐targeting therapies: modelling based on 5724 biomarker positive AD patients in the Swedish Registry of Cognitive Disorders
Authors: Jönsson Linus , Skillback Tobias , Kern Silke , Winblad Bengt , Blennow Kaj , Eriksdotter Maria , Zetterberg Henrik , Wimo Anders 
Published: December 2023

AbstractBackgroundLecanemab is an amyloid‐targeting therapy recently approved by the U.S. FDA for treatment of early Alzheimer’s disease. A phase III trial (Clarity AD) demonstrated a reduction of disease progression, however uncertainty remains around the long‐term health outcomes and implications for cost‐effectiveness. Previous economic evaluations have been limited by lack of long‐term follow‐up data on health outcomes and resource utilization in AD patients with biomarker‐confirmed amyloid pathology.Method5724 patients with longitudinal follow‐up data were included from the Swedish Registry of Cognitive Disorders (SveDem), linked to other data sources. Amyloid positivity was determined from the CSF beta amyloid 1‐42/p‐Tau ratio, with optimal cut‐off levels determined from Abeta 40/42 ratios. Patients were followed up to 12.9 years from diagnosis (mean 4.9 years). A disease model model was constructed with states defined by cognitive status (MCI/dementia, MMSE score) and care setting (community/institution). The semi‐Markov design allows transition probabilities to vary with time spend in individual states. Hazard rates for disease progression, institutionalization and mortality were estimated using semiparametric survival models based on SveDem linked to the municipal care and death registries. Costs by disease state were estimated from resource utilization data from the national patient and prescription drug registries on formal medical and community care. Health utility values by disease state were derived from previous observational studies in Sweden.ResultA therapy reducing disease progression to more severe cognitive states by 31% over a treatment period of 18 months (as in Clarity AD) was associated with savings in formal care costs of 41,000 SEK and 0.140 quality‐adjusted life‐years (QALYs) gained. At 1 million SEK per QALY, treatment would be cost‐effective at an annual cost of 121,000 SEK, including costs for diagnosis and monitoring. Almost half of estimated QALY gains were due to reduced mortality; setting survival equal in treated and untreated patients resulted in fewer QALYs gained but higher cost savings.ConclusionThis is the first study to report on the cost‐effectiveness of amyloid‐targeting therapy based on integrated disease progression and cost data from a large, representative cohort of amyloid‐positive early AD patients. Such data is of critical importance to enable cost‐effective introduction of lecanemab.
Choroid plexus volume, cognitive spectrum, and biomarkers of brain aging in older adults: The MIND‐China MRI Study
Authors: Song Lin , Li Yuanjing , Han Xiaodong , Wang Jiafeng , Li Chunyan , Cong Lin , Hou Tingting , Wang Yongxiang , Du Yifeng , Qiu Chengxuan 
Published: December 2023

AbstractBackgroundThe choroid plexus (CP) is a major source of cerebrospinal fluid (CSF) production that has been involved in clearance of CSF proteins and regulation of brain function, and possibly, in the pathogenesis of Alzheimer’s dementia. However, population‐based studies have not yet investigated the associations of CP volume with cognitive function and biomarkers of pathological brain aging in older adults.MethodThis population‐based cross‐sectional study included 1220 older adults (age ≥60 years) derived from the Multimodal INterventions to delay Dementia and disability in rural China, who underwent structural brain magnetic resonance imaging scans. CP was automatically segmented and quantified on 3T structural T1‐weighted images. Cognitive function was assessed using a neuropsychological test battery. Dementia, Alzheimer’s disease (AD), and mild cognitive impairment (MCI) were diagnosed following the international criteria. In the subsample (n = 905), we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL) using the Simoa platform. Data were analyzed with logistic and the general linear regression models.ResultIn the total sample (n = 1220), 275 persons were diagnosed with MCI (22.54%), 30 with all‐cause dementia (2.46%), and 26 with AD (2.13%). Controlling for demographics, total intracranial volumes (ICV), cardiovascular risk factors and related disorders, and APOE genotype, larger CP volume was significantly associated with increased likelihoods of dementia (adjusted odds ratio = 2.12; 95% CI = 1.33‐3.36), AD (2.28; 1.37‐3.80), and MCI (1.27; 1.07‐1.50). In addition, larger CP volume was significantly associated with lower z‐scores of verbal fluency, executive function, and global cognition (p<0.05). Furthermore, larger CP volume was associated with smaller volumes of total gray matter and hippocampus, and greater volumes of lateral ventricles, global white matter hyperintensity (WMH), and periventricular WMH (p<0.05). In the plasma subsample, larger CP volume was significantly associated with higher plasma Aβ42 concentration (p<0.05), and marginally with higher plasma Aβ40 concentration (p = 0.07).ConclusionLarge CP volume is associated with poor performance across the cognitive continuum as well as with biomarkers of cerebral atrophic, neurodegenerative, and microvascular lesions in older adults.
Results from the Systematic Multi‐domain Alzheimer’s Risk Reduction Trial (SMARRT): A Personalized Approach
Authors: Yaffe Kristine , Vittinghoff Eric , Dublin Sascha , Peltz Carrie , Fleckenstein Lynn E , Rosenberg Dori E , Barnes Deborah E , Balderson Benjamin H , Larson Eric B 
Published: December 2023

AbstractBackgroundModifiable risk factors are hypothesized to account for 30‐40% of dementia; yet, few trials have demonstrated that risk reduction interventions, especially multi‐domain, improve risk factors or cognition. We conducted the Systematic Multi‐domain Alzheimer’s Risk Reduction Trial (SMARRT), a 2‐year personalized, pragmatic risk reduction intervention.MethodsWe recruited 172 adults at elevated risk for dementia (age 70‐89 and ≥ 2 targeted risk factors) from primary care clinics of Kaiser Permanente Washington. Participants were randomly assigned to the SMARRT intervention (personalized risk reduction goals with health/nurse coaching) or to Health Education (HE) control. The primary outcome was change in a composite modified Neuropsychological Test Battery (mNTB); pre‐planned secondary outcomes were change in risk factors and quality of life. Outcomes were assessed at baseline, 6, 12, 18, and 24 months (initially in person, then due to COVID‐19, by phone). We used linear mixed models to compare, by intention‐to‐treat, changes from baseline averaged over the four follow‐up assessments.ResultsParticipants had a mean age of 75.7 years (sd 4.8), 63% were women and 81% non‐Hispanic White. After 2 years, compared to the 90 in the HE control, the 82 adults assigned to SMARRT demonstrated larger improvements in the composite cognitive score (average treatment effect 0.15 SD; 95% CI 0.04‐0.26, p = 0.008; an 80% improvement compared to HE change), better composite risk factor score (average treatment effect 0.11 SD; 95% CI 0.02‐0.21, p = 0.02) and improved quality of life (average treatment effect 1.11 points; 95% CI 0.08‐2.14, p = 0.03). There were no between‐group differences in serious adverse events or SAEs (HE = 23, SMARRT = 24, p = 0.59), but the intervention group had greater treatment related AEs such as musculoskeletal pain (14 vs. 0, p<0.001). Both groups expressed high level of satisfaction with the trial with greater satisfaction in intervention arm.ConclusionA 2‐year personalized, multidomain intervention led to modest improvements on cognition, most targeted risk factors, and quality of life. Modifiable risk reduction strategies should be considered for older adults at risk for dementia.