Basic Science and Pathogenesis.

Background: Optimal cerebral blood flow is crucial to maintaining cognitive function. Cerebrovascular reactivity (CVR) is a dynamic measure of cerebrovascular function which represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli. Prior studies have demonstrated an association between impaired CVR and cognitive function in cerebrovascular and neurodegenerative conditions, including cerebral amyloid angiopathy and Alzheimer disease.

Clinical Manifestations.

Background: Neuropsychiatric symptoms (NPS) are common in patients who develop dementia before the age of 65 years, defined as early-onset dementia (EoD). NPS are a major source of morbidity and caregiver distress in patients living with EoD. The prevalence, severity and types of NPS in different populations are unclear.

Clinical Manifestations.

Promoting emotional well-being (EWB) in older adults at risk for Alzheimer's Disease (AD), for example those with mild behavioral impairment (MBI), mild cognitive impairment (MCI), or subjective cognitive decline (SCD), is important both to improve quality of life and slow the progress of cognitive decline. Understanding how the early accumulation of AD pathology affects EWB and developing interventions to improve EWB both require the precise measurement of affective experience that plays a key role in EWB. Day to day affective experiences, both positive and negative, contribute significantly to EWB, but how affective experience maps onto EWB is complex.

Clinical Manifestations.

Background: Early detection and personalized care for Alzheimer's Disease (AD) mitigate the devastating consequences for millions of people around the globe. In the current scenario, there is a lack of user-friendly AI applications for predicting and understanding the progression of AD. The application should address the critical need for a predictive analytics tool that offers timely and transparent insights by utilizing the patient data.

Clinical Manifestations.

Background: Clinical trials in Alzheimer's Disease (AD) suffer from high failure rates, in part due to imprecision in endpoint measurements that introduces noise. SIA is a quantitative approach that utilizes algorithms to identify inconsistencies in measurements that may be indicative of problematic scale administration and/or scoring errors. The CDR, a sole primary and key secondary endpoint in many AD trials, can be challenging to score, particularly in early symptomatic and mild diseases.

Clinical Manifestations.

Background: Families with a history of Alzheimer's Disease (AD) may have a genetic predisposition that raises the risk of developing the condition. However, not all members of these families can undergo genetic testing. Thus, this study aims to evaluate specific cognitive changes, neuropsychiatric symptoms (NPS), and personality traits that may act as early indicators of AD in family members compared to controls.

Clinical Manifestations.

Background: Changes in speech and language functions have shown to be early symptoms of AD pathology. Recent developments in automatic speech and language processing have opened avenues for objective assessments of these changes. The primary objective of this study is to explore whether speech and language markers extracted from cognitive testing conducted during an automated phone call differ according to underlying AD pathology as measured in cerebrospinal fluid (CSF) in preclinical or early stage individuals.

Clinical Manifestations.

Background: The ability to detect cognitive impairment from Alzheimer Disease (AD) in its earliest possible symptomatic stage is a highly desirable characteristic for neuropsychological measures. Because early cognitive changes are often subtle, measures with high sensitivity are of great importance. Variability in attention, often assessed using reaction time (RT) tasks, have been shown to discriminate between cognitively normal older individuals with and without positive AD biomarkers and is correlated with biological markers of neurodegeneration.

Clinical Manifestations.

Background: Previous studies have linked impaired odor identification and global cognition with increased risk of cognitive decline and transition to dementia. However, the reverse question remains: if individuals have intact performance on these measures, are they at reduced risk for transition? We aimed to examine the accuracy of intact odor identification and global cognition for identifying lack of transition to dementia/cognitive decline using the population-based Mayo Clinic Study of Aging and compare their accuracy against and in combination with amyloid PET (Positron Emission Tomography).

Method: n = 647 participants age≥55 without dementia completed at baseline the Brief Smell Identification Test (BSIT; 'Intact' = 9-12), Blessed Information-Memory-Concentration Test (BIMCT; 'Intact' = 18-20,), and amyloid PET ('Normal/Intact' SUVR<1.

Clinical Manifestations.

Background: Objective Subtle Cognitive Decline (obj-SCD) can be identified through standardized neuropsychological tests and may precede the development of Mild Cognitive Impairment (MCI). Nevertheless, current clinical and research criteria lack a standardized protocol for identifying obj-SCD. This study introduces cutting-edge sensitive methods to characterize obj-SCD, defined through Alzheimer's disease (AD) biomarker-based longitudinal cognitive performance in episodic memory.

Clinical Manifestations.

Background: Interest in use of digital technology to advance AD/ADRD research has been growing exponentially over the last few years. This acceleration is fueled in part by growing awareness that both well used research methods as well as newer biomarker approaches are 1) inadequate for clinical symptom detection in the earliest stages of an insidious onset disease and 2) have resulted in inaccurate as well as biased data that is generating treatment and prevention solutions that are insufficiently relevant to some and potentially not relevant to many.

Methods: Sensors embedded in mobile devices such as smartphones and wearables deliver a high penetration, low-cost solution for overcoming previous limitations of early detection sensitivity and limited representative reach.

Basic Science and Pathogenesis.

Background: Frontotemporal lobar degeneration (FTLD)- TAR DNA-binding protein 43 (TDP) type C is commonly associated with a clinical diagnosis of semantic dementia (SD). Although anterior temporal lobe (ATL) is one of the primary atrophy centers, it is yet to be defined which other areas are involved in the TDP-type C pathology early in the disease course.

Methods: We included 16 patients with autopsy-confirmed FTLD-TDP type C from the database of the UCSF Memory and Aging Center: 13 patients with semantic variant primary progressive aphasia (svPPA) and predominant left ATL atrophy, and 3 patients with semantic behavioral variant frontotemporal dementia (sbvFTD) and predominant right ATL atrophy.

Clinical Manifestations.

Background: Assessments for early-stage Alzheimer's disease (AD) aim to identify neuropsychological and functional impairments, which rarely correlate with early disease stages. We need to enhance our understanding of the cognitive aspects contributing to functional decline to improve sensitivity in functional assessment. The ability to bind information in memory declines in preclinical AD stages.

Clinical Manifestations.

Background: The intricate and heterogeneous phenotypes associated with neuropsychiatric symptoms (NPSs) encumber exploration of their role in the neuropathology and underlying biological mechanisms of Alzheimer's disease (AD) continuum.

Method: An individual-level Regional Radiomics Similarity Network (R2SN) for 487 patients with AD continuum (376 with NPSs vs. 111 without NPSs) were developed to find the R2SN connections associated with NPSs and refine the subtypes of NPS in the AD continuum.

Clinical Manifestations.

Background: Early identification of preclinical Alzheimer's disease (AD) is key to timely interventions. However, existing neuropsychological test scores are not sensitive to subtle cognitive decline during preclinical AD. There is a need to develop cognitive measures that are more sensitive to early stages of decline.

Clinical Manifestations.

Background: The Alzheimer's Association recommends early screening of Alzheimer's disease and related dementias(ADRD), urging the development of biomarkers and other tools for early risk/detection. However, the general public's willingness to be tested for early ADRD must be considered, particularly among minoritized populations. For example, Black older adults within the United States (U.

Clinical Manifestations.

Background: Game-based Cognitive Assessment - 3-Minute Version (G3) is a WeChat mini-program developed for the early screening of cognitive impairments in Chinese older adults. It consists of three game-like digital cognitive tests, namely "Number Ordering", "Species Sorting", and "Gold Finding". This study aims to assess the sensitivity, specificity, and diagnostic accuracy of G3 in detecting mild cognitive impairment (MCI) and early-stage dementia in Chinese older adults.

Clinical Manifestations.

Background: Individuals with Down syndrome (DS) typically develop Alzheimer's disease (AD) at an early age. Estimates of the age of decline vary, but typically place it in the early-mid 50s. As AD onset can be difficult to identify in intellectually impaired cohorts, understanding the expected timing of decline may help individuals and caregivers prepare.

Clinical Manifestations.

Background: Nutrition and other lifestyle interventions hold promise for reducing dementia risk; however, significant barriers remain in translating these programs and recommendations to individuals at the greatest risk. We discuss application of the NIH Obesity-Related Behavioral Intervention Trials (ORBIT) to the development and tailoring of a nutrition program for high-risk older adults.

Method: A mixed methods approach was used to evaluate factors that contribute to adherence and engagement with the nutrition program.

Clinical Manifestations.

Background: Spatial orientation involves egocentric and allocentric strategies that switch in the brain. Disturbances in switching may indicate Neurocognitive Disorders, which contribute to early detection of Alzheimer's Disease. The "Ego-Allo-Switching Task" (EAST) needs to be adapted for cross-cultural use in Brazil.

Clinical Manifestations.

Background: Women are more likely to experience sleep problems than men, especially during and after menopausal transition. Sleep disturbances are related to memory decline and the development of Alzheimer's disease (AD), which is also more common among women. While research on habitual sleep patterns in aging has largely focused on mean sleep outcomes across nights, few studies have examined the potentially harmful effects of night-to-night variability in sleep quality on AD biomarkers and memory function.

Clinical Manifestations.

A critical need exists to find simpler approaches for early detection of Alzheimer disease (AD) and related dementias. These approaches must increase access to preventative interventions and treatments, both pharmacological and non-pharmacological, for people in preclinical and prodromal stages of disease. This need has been amplified by the emergence of disease modifying therapies (DMTs), which require biological confirmation of amyloid-ß positivity.

Clinical Manifestations.

Background: Neuropsychiatric symptoms (NPS) are common in early stages of Alzheimer's disease (AD) and may be early markers of cognitive decline and dementia in older individuals. The Mild Behavioral Impairment Checklist (MBI-C) was developed to capture new-onset transdiagnostic NPS in individuals at risk of dementia. We sought to determine whether mild behavioral impairment symptoms are elevated in non-demented Presenilin-1 (PSEN1) E280A carriers, who are genetically determined to develop dementia by their 50s.

Clinical Manifestations.

Background: Mild parkinsonian signs (MPS) are prevalent in older adults and linked to an increased risk of dementia. However, their association with Motoric Cognitive Risk syndrome (MCR), a pre-dementia syndrome characterized by slow gait speed and cognitive complaints, is unclear. This study aims to examine the association of MPS with incident MCR.