Biomarkers.

Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without β-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

Biomarkers.

Background: Semantic memory refers to knowledge of attributes associated with common objects. Quantifying the strength of semantic association between successive 'animal' fluency responses can be challenging. The current research assessed between-group differences for 'animal' fluency total output and selected verbal serial list learning, episodic memory measures.

Biomarkers.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles which cause neurodegeneration and cognitive decline1. APOE-ε4 is identified as the first common genetic risk factor with high penetrance in the early onset of AD3. ABCA7 (rs115550680) (ABCA7-80) is associated with the development of late-onset AD among African Americans2.

Biomarkers.

Background: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, dropout artifacts are present in some modalities, leading to poor image quality and unreliable segmentation of MTL subregions. Considering that MRI modalities with different field strength offer distinct advantages in imaging different parts of the MTL, we developed a muti-modality segmentation model using both 7-tesla (7T) and 3-tesla (3T) structural MRI to obtain robust segmentation in poor-quality images.

Developing Topics.

Background: Neuropsychiatric symptoms (NPS) including depression and apathy, are common in dementia and profoundly affect both patients and caregivers. These symptoms can manifest early and can be indicative of the disease progression. The existing tools for measuring NPS lack objectivity and are not sensitive enough to detect subtle changes in the earlier stages of dementia.

Developing Topics.

Background: While people of Middle Eastern/North African (MENA) or South Asian descent constitute a rapidly growing segment of the aging population, they are underrepresented in Alzheimer's disease and related dementias (ADRD) research. This is concerning because dementia risk factors, both modifiable such as diabetes, and non-modifiable such as the APOE4 genotype, vary among populations due to environmental and evolutionary differences. Exposure to these risk factors during midlife is particularly crucial, significantly increasing the likelihood of dementia later in life.

Developing Topics.

Background: Alzheimer's disease (AD) is the leading cause of cognitive impairment and dementia with rising prevalence, morbidity, and mortality. Limited treatment options highlight a significant unmet need. AD is characterized pathologically by extracellular accumulation of Aβ peptide-containing plaques and intracellular neurofibrillary tangles containing aggregates of the microtubule-associated protein tau, leading to neuronal and synaptic loss, neuroinflammation, and brain atrophy.

Developing Topics.

Background: Agitation, manifesting as aggressive and non-aggressive behaviors, is one of the most common neuropsychiatric symptoms in Alzheimer's dementia, presenting in approximately half of all patients. Despite the high prevalence, recognition of agitation in Alzheimer's dementia (AAD) remains a challenge that impacts timely diagnosis and treatment. The International Psychogeriatric Association (IPA) established a new standard definition of agitation in cognitive disorders, which provides guidance for advancing recognition and improving patient care.

Developing Topics.

Background: The β-secretase-1 inhibitors (BACEi), including verubecestat, were extensively studied in prodromal to moderate AD and demonstrated early cognitive decline (negative effect) at doses achieving >50% inhibition of amyloid production. Questions remain as to whether BACEi may still have utility, if used earlier in disease and at lower levels of inhibition. A mechanistic model of the progression of Alzheimer's disease was used to predict effects of alternative BACEi therapeutic approaches on disease progression.

Developing Topics.

Background: By inhibiting the translation of neurotoxic aggregating proteins - amyloid precursor protein, tau, alpha-synuclein etc., buntanetap restores axonal transport, lowers inflammation, and protects nerve cells from dying. Our Phase2 studies showed that buntanetap improved early AD patients ADAS-Cog11 after a month treatment.

Developing Topics.

Background: Increased levels of the light chain of neurofilament (NfL) in human cerebrospinal fluid indicate axonal damage. Their determination can support laboratory diagnosis and monitoring of neurological diseases associated with axonal damage. We developed a prototype chemiluminescence assay (ChLIA) and an enzyme-linked immunoassay (ELISA, research use only) to detect NfL and report their analytical agreement with an established ELISA.

Developing Topics.

Background: We developed a highly sensitive immunoassay method using lecanemab that selectively captures amyloid-β (Aβ) protofibril (PF). To characterize Aβ-PF in human cerebrospinal fluid (CSF), we investigated the CSF Aβ-PF levels in patients with Alzheimer's disease (AD) at different disease stages. We also studied the association of CSF Aβ-PF with other AD-related biomarkers.

Developing Topics.

Background: The medial temporal lobe (MTL) is the earliest region to display atrophy in Alzheimer's disease (AD). Apolipoprotein E (APOE-ε4) and ABCA7-80 (rs115550680), two genes involved in lipid metabolism, are the strongest heritable contributors to AD in African Americans. However, the longitudinal influence of these genes on MTL dynamic network flexibility, a novel neuroimaging marker of preclinical AD, is unknown.

Developing Topics.

Background: Cholinergic innervation is particularly vulnerable in many neurodegenerative diseases such as Alzheimer's diseases. Nerve growth factor (NGF) plays a major role in the maintenance and function of cholinergic neurons, and a decrease in trophic signalling by NGF-Tropomyosin receptor kinase A (TrkA) contributes to cholinergic and synaptic degeneration. E2511 is a novel small molecule TrkA biased positive allosteric modulator showing an increase in specific trophic signalling via direct binding to TrkA with a potential to recover and reinnervate damaged cholinergic neurons.

Developing Topics.

Background: Older African Americans bear a disproportionate burden of both sleep problems and cognitive dysfunction. Alarmingly, poorer sleep health may put an individual at higher risk of cognitive dysfunction. However, the relationship between sleep and cognition in older African Americans continues to be understudied.

Developing Topics.

Background: Alzheimer's disease (AD) is defined by the presence of ß-amyloid (Aß) plaques and tau-based neurofibrillary tangles (NFTs). Understanding the temporal relationship of NFTs with atrophy in early AD regions, specifically the medial temporal lobe (MTL), is critical for monitoring disease progression. Accumulation of NFTs has been suggested to precede atrophy because cross-sectional measures of atrophy are more weakly associated with baseline tracer uptake than prospective longitudinal ones.

Developing Topics.

Background: Cognitive function alterations are a feature of the cognitive aging process. Additionally, aging is marked by macro- and micro-structural changes in the brain, such as gray matter (GM) atrophy, iron accumulation, and demyelination. This study explores the association between cognitive function and cooccurrence of brain micro- and macro-structural changes in healthy older adults.

Developing Topics.

Background: Lecanemab is a humanized immunoglobulin G1 monoclonal antibody targeting neurotoxic Aβ protofibrils and Aβ plaques, which reduces markers of amyloid and significantly slows clinical decline on multiple cognition and function measures. Cerebrospinal fluid (CSF) microtubule-binding region (MTBR) of tau containing the residue 243 (MTBR-tau243) is an emerging tau pathology biomarker that tracks with tangle formation in Alzheimer's disease (AD) [Horie et al. Nat Med.

Developing Topics.

Background: PET quantification of brain tau pathology aids in Alzheimer's disease staging and patient screening. This study assesses whether the phosphorylated to nonphosphorylated plasma Tau217 ratio (pTau217R) predicts regional tau PET standardized uptake value ratio (SUVR) and accurately identifies subjects with different levels of tau accumulation.

Method: Plasma pTau217 and non-phosphorylated tau217 concentrations were quantified via immunoprecipitation-mass spectrometry.

Developing Topics.

Background: African Americans bear a disproportionate burden of both cardiovascular diseases and Alzheimer's disease (AD). Assessment of the Five-Factor personality dimensions-Neuroticism, Extroversion, Openness, Agreeableness, and Conscientiousness, particularly, higher levels of neuroticism-is linked to greater adverse cardiovascular and cognitive outcomes, including AD. Generalization-the ability to apply prior learning to new circumstances-is presented as a putative cognitive marker for the earliest stages of preclinical AD.

Developing Topics.

Background: African Americans are at increased risk for cardiovascular-related health problems (e.g., hypertension, cardiovascular disease, stroke, obesity) and cognitive dysfunction, including Alzheimer's disease (AD).

Developing Topics.

Background: A typical paper/pencil neuropsychological evaluation to assess for mild cognitive impairment (MCI) and dementia is lengthy. There is a need for a brief, digitally administered/scored neuropsychological protocol that can differentiate patients who are cognitively normal versus MCI and dementia. This need is particularly acute with the advent of disease-modifying medications to treat MCI and early Alzheimer's disease (AD).

Alzheimer's Imaging Consortium.

Background: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, dropout artifacts are present in some modalities, leading to poor image quality and unreliable segmentation of MTL subregions. Considering that MRI modalities with different field strength offer distinct advantages in imaging different parts of the MTL, we developed a muti-modality segmentation model using both 7-tesla (7T) and 3-tesla (3T) structural MRI to obtain robust segmentation in poor-quality images.

Alzheimer's Imaging Consortium.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid plaques and neurofibrillary tangles which cause neurodegeneration and cognitive decline1. APOE-ε4 is identified as the first common genetic risk factor with high penetrance in the early onset of AD3. ABCA7 (rs115550680) (ABCA7-80) is associated with the development of late-onset AD among African Americans2.

Alzheimer's Imaging Consortium.

Background: The recent breakthrough in monoclonal antibody treatment for Alzheimer's disease (AD) has ushered in a new phase in AD healthcare. However, associated amyloid-related imaging abnormalities (ARIA) present a significant risk to patients, necessitating careful monitoring. Detection by radiologists can be challenging and may suffer from inconsistency.