bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurophysiological changes associated with plasma p‐tau represent functional effects of amyloid accumulation and are modulated by APOE.
Authors: Ranasinghe Kamalini G , Rojas Julio C. , Casaletto Kaitlin B. , Kudo Kiwamu , Syed Faatimah , La Joie Renaud , Chan Brandon , Lago Argentina Lario , Miller Bruce L , Vossel Keith , Kramer Joel H. , Boxer Adam L. , Rankin Katherine P , Rabinovici Gil D. , Nagarajan Srikantan S 
Published: December 2023

AbstractBackgroundAlzheimer disease (AD) is defined by the presence of cerebral amyloid‐β plaques and tau neurofibrillary tangles (NFT). Neurophysiological manifestations which depict the functional changes of neurons and circuits, demonstrate that amyloid‐β and tau have distinct effects—high cerebral amyloid‐β burden is associated with increased neural oscillatory activity while high tau burden with decreased activity. With the recent proliferation of fluid biomarkers, plasma p‐tau181 is known to reflect accumulation of amyloid‐β as well as tau, detected from molecular imaging and neuropathological analyses. It remains unknown whether the neurophysiological consequences of soluble p‐tau reflects the effects of amyloid‐β or those of NFT.MethodWe used multimodal imaging combining magnetoencephalography (MEG) to cross‐sectionally study the spectral signatures and positron emission tomography with Aβ binding tracers to define the global amyloid burden in early‐stage neuropathological spectrum including Aβ+ cognitively‐unimpaired (CU, n = 9), Aβ+ mild‐cognitive‐impairment (MCI, n = 20), and Aβ‐negative CU controls (n = 45). Plasma p‐tau181 and neurofilament light (NFL) were measured with Simoa. Using statistical mixed models we examined the associations of neural oscillatory signatures with plasma p‐tau181 and NFL.ResultThe characteristic oscillatory signature of increased delta‐theta and reduced alpha spectrum were detectable even in the earliest stages of global amyloid accumulation (Aβ+CU vs. Aβ‐CU; Fig.1). Increased p‐tau181 was associated with increased spectral signatures across the frequency spectrum in Aβ+ individuals (Fig.2). These positive correlations were more robust within delta‐theta (2‐7Hz) than alpha (8‐12 Hz) spectrum. Plasma NFL in Aβ+ individuals, in contrast, was associated with reduced spectral signatures. We also found APOE‐ɛ4 carriers have greater degree of neurodegeneration which modulated the associations between p‐tau181 and neural oscillations (Fig.3).ConclusionPrevious neurophysiological studies have demonstrated that Aβ accumulation is associated with increased oscillatory activity while tau accumulation is associated with reduced oscillatory activity. Positive correlations of p‐tau181 across the spectrum is therefore consistent with the effects of Aβ accumulation and not with tau accumulation. Plasm NFL may represent early effects of neurodegeneration. Collectively our findings indicate that p‐tau181 reflects earliest functional effects of Aβ rather than tau and have implications for the interpretation of plasma p‐tau along the AT(N) stages.
Applying the Boot Camp Translation Method to Increase Alzheimer’s Disease Awareness in the Houston Hispanic/Latino Community
Authors: Arroyo‐Miranda Mirna L , Martinez Michelle N 
Published: December 2023

AbstractBackgroundDespite increased risk for Alzheimer’s disease and related dementias (ADRD), Hispanics/Latinos (H/Ls) continue to be underrepresented in ADRD research. H/Ls comprise over 40% of the population in the Houston, Texas, metropolitan area. We engaged Houston H/L middle‐ and older‐age community members through a “Boot Camp Translation” (BCT), a community engaged strategy, to co‐create culturally‐responsive materials on ADRD awareness and risk reduction.MethodTwenty ADRD stakeholder organizations yielded 12 participants 35 y/o and older (Median age: 50 y/o). Participants met in three, 4‐hour virtual sessions and several phone conferences from February to June 2021. After an informative kick‐off session on ADRD clinical manifestations, epidemiology and risk reduction, participants answered these questions throughout the process: 1) main message(s) on AD for the Houston H/L community, 2) targeted audience, and 3) best method(s) to convey the message. After the process, BCT participants were invited to become part of a Community Action Board (CAB).ResultNine adults completed the BCT process. Compared to baseline, participants demonstrated improved subjective understanding and objective knowledge of ADRD at the end of the process. Local messaging centered around brain health to reduce AD stigma, importance of geriatric education for care providers, and self‐care in caregiving. Targeted audiences were the general H/L population across the lifespan, care providers and caregivers. Dissemination strategies focused on family and intergenerational relationships, with imagery and colors reflecting the diversity and vibrancy of the Houston H/L community. Final products included a “telenovela‐style” educational video series, and other graphic/ printed materials. Four of the nine participants remain active in the CAB at one year post BCT.ConclusionBoot Camp Translation is an effective way to build community trust, and design culturally relevant AD messaging. Experience was positive overall; participants developed a sense of ownership of the process, and created an atmosphere of cooperation and solidarity.
Neuropathological characterization of PiB binding in postmortem striatum in Down syndrome
Authors: Rouanet Jeremy P. , Shamas Tamara , Ngo Kim Chan , Phelan Brenna , Pascual Jesse R. , Andrews Elizabeth J. , Phelan Michael J. , Ikonomovic Milos D , Head Elizabeth ,   Alzheimer’s Biomarker Consortium‐Down Syndrome (ABC‐DS)
Published: December 2023

AbstractBackgroundAmyloid‐beta plaques form in the brain throughout life in people with Down syndrome (DS) and are one of the hallmarks of Alzheimer disease (AD) neuropathology. The regional progression of amyloid buildup in DS is similar to that of late onset AD (LOAD) in the neurotypical population. The development of positron emission tomography (PET) ligands like Pittsburgh Compound B (PiB) has allowed researchers and clinicians to visualize and track amyloid accumulation in the brain throughout life. Using this technology, a unique pattern emerges in people with DS, where the earliest and strongest PiB PET retention is in the striatum, unlike LOAD but similar to autosomal dominant AD. Frontal cortex PiB PET retention is similar in all groups. We used a fluorescent derivative of PiB, cyano‐PiB (CN‐PiB), to investigate PiB labeling postmortem in DS striatum. We hypothesized that striatal CN‐PiB load increases with age and is greater than in the frontal cortex, similar to observations from PiB PET studies of adults with DS.MethodWe conducted CN‐PiB labeling in postmortem striatum and frontal cortex from 44 cases with DS ages ranging from 42 to 70 years (25F/19M, mean PMI 7.4 hours). Whole slide imaging and automated image analysis were used to derive individual plaque‐level information regarding load, size, and distribution of CN‐PiB+ plaques in DS with age.ResultCN‐PiB labeled plaques in both the striatum and frontal cortex were also positive for amyloid‐beta antibodies targeting epitopes 1‐16, 17‐24, and x‐42. Preliminary data suggest that striatal CN‐PiB load (median = 2.3%) is not higher compared to the frontal cortex in DS (median = 10%). Striatal CN‐PiB load did not change with age from 42 to 70 years, suggesting an early saturation (IQR = 3.5%).ConclusionCN‐PiB labeled amyloid‐beta plaque load in the striatum in DS is comparable to conventional neuropathologic analysis and does not differ from frontal cortical load. Other aspects of PiB‐binding or pathologies may contribute to the early and prominent striatal PiB PET retention reported in DS. It will be important in future studies to include younger cases with DS.
Elevated Carotid Pulse Wave Velocity is associated with Cognitive Impairment and Cerebral Amyloid Deposition: A Phase‐Contrast MRI Study
Authors: Tang Jianing , Pahlavian Soroush Heidari , Joe Elizabeth B , Terner Jamie , Braskie Meredith N , Marmarelis Vasilis , Chui Helena C , Yan Lirong 
Published: December 2023

AbstractBackgroundPrevious studies have indicated that arterial stiffness could play an important role in the AD pathology. Arterial stiffness is typically measured by pulse wave velocity (PWV) from central and peripheral arteries. Recent work has introduced a two‐minute robust MRI method to measure carotid PWV (cPWV) using a single‐slice oblique‐sagittal phase‐contrast MRI(OS PC‐MRI)[Pahlavian SH et al, JCBFM 2021]. This study aims to evaluate cPWV measured by OS PC‐MRI as a sensitive imaging marker of AD by studying the association of cPWV with cognitive performance and amyloid pathology.MethodTwenty‐three elderly volunteers (13 female, 72.6 ± 7.1 years) participated in the study and underwent cognitive and functional assessments including Clinical Dementia Rating (CDR, n = 23), Mini‐Mental State Exam (MMSE, n = 21), and Montreal Cognitive Assessment (MoCA, n = 23) and F18‐florbetaben amyloid‐PET scans (n = 14). A retrospectively gated single‐slice 2D OS PC‐MRI was performed on each participant at 3T to assess cPWV. The correlations between cPWV vs cognitive measures and cerebral amyloid were calculated across subjects using Pearson or Spearman’s correlation coefficients.ResultTable 1 lists the demographic and clinical information of participants. cPWV showed significant negative correlations with both MoCA (Figure 1a) and MMSE (Figure 1b) (cPWV vs. MoCA: r = ‐0.57, p = 0.0044; cPWV vs. MMSE: r = ‐0.74, p < 0.001;), and correlations remained significant after controlling for age, gender, years of education (cPWV vs. MoCA:r = ‐0.70, p < 0.001; cPWV vs. MMSE: r = ‐0.75, p < 0.001). Participants were further separated into two groups (CRD = 0: n = 12; CDR> = 0.5: n = 11) based on their CDR scores. cPWV values were significantly higher in the group with CDR> = 0.5 without and with correcting for age, sex, and educational level (p = 0.0019, p = 0.015) (Figure 1c). Individuals who presented with amyloid pathology had higher cPWV compared to the ones without amyloid pathology (p = 0.038) (Figure 2), which indicates cPWV may be closely linked to amyloid pathology in AD.ConclusionThis study demonstrates that elevated carotid PWV is associated with cognitive impairment and amyloid pathology in elderly adults. Longitudinal studies are necessary to determine whether cPWV contributes to accumulation of amyloid in brain parenchyma or results from deposition of amyloid in cerebral blood vessels.
Association of focal epilepsy in Alzheimer’s disease with tau, amyloid, and neurodegeneration
Authors: Lam Alice D , Jacobs Heidi I.L. , Thibault Emma G. , Mayblyum Danielle V. , Hsieh Stephanie , Pellerin Kyle R , Buss Stephanie S. , Sarkis Rani A , Johnson Keith A. , Sperling Reisa A. 
Published: December 2023

AbstractBackgroundNetwork hyperexcitability has emerged as an important contributor to cognitive dysfunction and clinical progression in Alzheimer’s disease (AD), with work in animal AD models supporting a mechanistic, feed‐forward link between neuronal hyperexcitability and amyloid and tau pathology. Seizures are a quintessential manifestation of network hyperexcitability in AD. AD is associated with a 2‐3‐fold increased risk of developing epilepsy, and epilepsy in AD is most often a focal, unilateral temporal lobe epilepsy. We hypothesized that if network hyperexcitability is mechanistically linked to AD pathology, then focal unitemporal hyperexcitability in individuals with AD and epilepsy would be associated with increased deposition of tau and/or amyloid within the epileptogenic hemisphere.MethodWe studied eight individuals with early clinical stages of AD who developed focal epilepsy early in the course of AD. All individuals underwent overnight scalp EEG, 3T structural brain MRI, and PET imaging with 11C‐PiB and 18F‐MK‐6240. We performed region‐of‐interest based imaging analyses and calculated asymmetry indices (AI) as: 200 * (Ipsilateral ‐ Contralateral) / (Ipsilateral + Contralateral), where ipsilateral and contralateral are relative to the epileptogenic hemisphere.ResultTau deposition was asymmetrically increased within the epileptogenic hemisphere. Individuals with a higher global tau burden showed asymmetrically increased tau in the lateral temporal lobe, medial and lateral parietal lobes, and frontal lobes of the epileptogenic hemisphere, while those with a lower global tau burden demonstrated a highly focal, discrete tau accumulation within the lateral temporal lobe. Amyloid deposition was also increased within the epileptogenic hemisphere, particularly in the lateral temporal, medial and lateral parietal, and frontal regions, though the magnitude of amyloid AI was lower than that of tau AI. We also found increased cortical atrophy in the lateral temporal and lateral parietal regions of the epileptogenic hemisphere.ConclusionOur study reveals a spatial association between focal epilepsy and asymmetries in tau and amyloid deposition and cortical atrophy in early clinical stages of AD. While historically, individuals with AD and epilepsy have been excluded from most studies in AD, our findings demonstrate that studying these individuals can provide unique insights on mechanisms that underlie the clinical and pathologic heterogeneity of AD.
Age of dementia onset and death in chronic traumatic encephalopathy
Authors: Ryder Megan H. , Abdolmohammadi Bobak , Daneshvar Daniel H , Martin Brett M , Palmisano Joseph N , Alvarez Victor E. , Huber Bertrand R. , Tripodis Yorghos , Stein Thor D. , Alosco Michael L , McKee Ann C. , Mez Jesse B. 
Published: December 2023

AbstractBackgroundChronic Traumatic Encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. The clinical presentation of CTE can include cognitive impairment, with progression to dementia. Currently, CTE can only be definitively diagnosed postmortem; most reports of the associated clinical syndrome come from retrospective informant interviews. In this setting, characterizing the clinical course can be biased because donors may have died from causes unrelated to CTE. To minimize this selection pressure and more accurately report average age of dementia and death in CTE, we identified brain donors with high stage CTE who died from neurodegenerative disease.MethodDonors with RHI exposure from contact sports and/or military service were eligible for the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank. CTE neuropathological diagnosis and staging were assessed using validated criteria. Dementia diagnosis was determined by clinical consensus and dementia onset age was defined as the age that informants first reported functional impairment on a standardized scale of activities of daily living (Functional Activities Questionnaire, FAQ). Causes of death were determined from medical records, death certificate review, and informant interviews. Donors with a neuropathological diagnosis of high stage CTE (III or IV) and a neurodegenerative cause of death were included in the current study.Result186 donors met inclusion criteria. Football was the most common type of RHI exposure (172; 92.5%). Mean age of dementia onset was 70.2 (SD = 7.4; range = 48‐93) and the mean age of death was 77.1 (SD = 7.8; range = 54‐97). Mean time from dementia diagnosis to death was 6.9 years (SD = 4.6; range = 0‐24). 136 donors (73.1%) had other comorbid neurodegenerative diseases, including 84 (45.4%) with Alzheimer’s disease, 58 (31.2%) with Lewy body disease, and 28 (15.1%) with frontotemporal lobar degeneration. Compared to donors with CTE and comorbid neurodegenerative diseases, donors with CTE but without comorbid neurodegenerative diseases did not significantly differ in age at dementia onset, age at death, and time from dementia diagnosis to death.ConclusionAmong brain donors with high stage CTE who died from neurodegenerative disease, approximately 75% had late onset‐dementia (i.e., age of dementia onset >65 years) and died within 10 years of dementia diagnosis.
Prescription profile of Alzheimer’s disease medications in the public health system in Southern Brazil
Authors: De Marco Maísa , Brandi Ana Laura , Krug Bárbara , Camozzato Analuiza , Picon Paulo Dornelles , Chaves Marcia L Fagundes , Castilhos Raphael Machado 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) accounts for 60‐70% of cases of dementia, and is characterized by progressive decline in cognition and functionality. Pharmacological treatment is fundamentally symptomatic, and consist mainly of three acetylcholinesterase (IChE) inhibitors (donepezil, galantamine and rivastigmine) and one N‐methyl‐D‐aspartate (NMDA) receptor, memantine. Although these drugs are freely available in the public health system in Brazil, there may be barriers to accessing them. We aim to evaluate the profile of prescription of AD medication in the public health system in the state of Rio Grande do Sul (RS), Southern Brazil.MethodsWe analyzed all AD medications requested in the state of RS during October/2021 in the public health system. Sociodemographic, Mini Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) scale data were collected. We described the variables as median (interquartile range ‐ IQR) or frequencies. We also performed a spatial autocorrelation analysis of the medication prescribed in the RS municipalities. All analyses were performed in R.ResultsThe total of 2,382 AD patients were using any AD medication. Most were female (65.6%), had elementary education (71.7%) and a median age of 79 (73‐84) years. The patients' MMSE median was 15 [12‐18] and most had a CDR = 2 (55.2%, 1133). The most prescribed medication was donepezil, 42.6% (1014), alone or in combination with memantine (Table 1). The distribution of the variable patient/100,000/municipality was clustered, with Moran’s I of 0.17562 (p<0.001) (Figure 1).ConclusionsMost patients using AD medications in the public health system had moderate dementia. The distribution pattern of these medications in the RS state was uneven. The identification of factors related to these patterns may provide valuable information about the barriers to the access to AD treatment in the state of RS.
The Validity of the Thai Electronic Version of the Montreal Cognitive Assessment (MoCA)
Authors: Hemrungrojn Solaphat , Amrapala Arisara , Kasemsantitham Arp‐Arpa , Dithanat Praphada , Lapanan Kulvara , Chaiyasurayakan Kanokwan , Assawatinna Ratiya , Phutrakool Phanupong , Punyabukkana Proadpran , Nupairoj Natawut ,   Cognitive fitness and technology in biopsychiatry research unit
Published: December 2023

AbstractElectronic cognitive assessment tools are essential in screening and managing patients’ disease progression in clinical practices. Neurocognitive disorders, particularly mild cognitive impairment (MCI) and Alzheimer’s Dementia (AD), can be assessed using the Montreal Cognitive Assessment (MoCA) [1, 2]. A digital version of the MoCA could help reduce the burden on healthcare providers, increase accessibility, and maximize its utility, especially in countries that lack medical staff such as Thailand. This pilot study aimed to establish the concurrent validity between the electronic version of the MoCA‐Thai (eMoCA‐Thai), developed by the authors of this paper, to the original paper‐and‐pencil version (MoCA‐Thai) in adults who are cognitively normal (CN), have MCI, and have AD. 54 adults between the ages of 60 to 90 attending a dementia clinic were administered both the eMoCA‐Thai and the standard MoCA‐Thai one week apart. The primary outcome measures include the total scores and all subscale scores of the two test versions. Correlations and differences between scores were analyzed using concordance correlation coefficients (CCC) and various parametric t‐tests. Results show that there is high correlation for total MoCA scores with a CCC of 0.919 and a mean difference of ‐0.204 (‐6.311, 5.904). All the cognitive subdomain scores had moderate to high CCC of more than 0.4. The differences in average total score (22.81±7.49 for the MoCA‐Thai and 23.02±7.99 for the eMoCA‐Thai) were not statistically significant (p = 0.633), indicating no differences between the MoCA scores of both versions. When comparing total MoCA scores between participant groups, both CN and MCI had acceptable correlations (CCC >0.2) with a mean difference of 0.355 (‐4.720, 5.429) and ‐1.643 (9.001, 5.715), respectively, whilst AD had excellent correlation (CC >0.8) with a mean difference of 0.111 (‐6.496, 6.717). Subdomain scores between participant groups were not statistically significantly different except for Delayed Recall for all participants combined (p<0.05). In conclusion, there is adequate concurrent validity between the MoCA‐Thai and eMoCA‐Thai, making it a useful tool to help improve workflow and increase accessibility.
Amyloid‐Beta PET Synthesis from Structural MRI: A Potential Alternative Method for Alzheimer’s Disease Screening
Authors: Vega Fernando , Addeh Abdoljalil , MacDonald M. Ethan 
Published: December 2023

AbstractBackgroundAmyloid‐beta and structural brain atrophy are known to be hallmarks of Alzheimer’s Disease (AD), and can be quantified with Positron Emission Tomography (PET) and structural Magnetic Resonance (MRI), respectively. PET scans use radiotracers that binds to amyloid‐beta molecules, whereas MRI measures changes in structural morphology. PET scans are difficult to perform due to cost (∼$5000/scan), invasiveness, and ionizing radiation exposure, making them inaccessible for screening early‐onset AD. Conversely, MRI is a cheaper (∼$500/scan), non‐invasive, and free from ionizing radiation technique, however, it cannot provide molecular information obtained from PET. There is a known relationship between amyloid‐beta and brain atrophy, hence, amyloid‐beta PET images might be synthesized from structural MRI using image translation, which is an advanced form of machine learning.MethodAn image translation algorithm was developed using the Open Access Series of Imaging Studies (OASIS‐3) dataset that provides 929 subjects with pairs of T1‐weighted MRI and amyloid‐beta PET images, where 609 are cognitively normal (CN) and 489 at different stages of cognitive decline based on Clinical Dementia Rating scores. The image translation algorithm implemented with Conditional Generative Adversarial Networks, shown in Figure 1, was trained with 550 pairs with 156 axial slices each of amyloid‐beta and MRI images. Eight models where generated with different parameters to assess their impact in the generalization quality, then compared in a sample of 334 subjects using Structural Similarity Index (SSIM) and Peak Signal‐to‐Noise Ratio (PSNR).ResultFigure 2, compares the models performance based on SSIM and PSNR, where the best performing model generates synthetic PET images with a high degree of similarity with the real ones in Figure 3.ConclusionAn image translation pipeline was implemented and explored by changing parameters that can affect the model performance, the developed models are robust against the different parameters that were changed and it demonstrates that amyloid‐beta PET images can be synthesized from structural MRI, reducing cost, invasiveness and increasing availability. Such a method could enable non‐invasive screening of early onset AD.