Connectivity, Pathology, and ApoE4 Interactions Predict Longitudinal Tau Spatial Progression and Memory.

Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults.

Tau accumulation and atrophy predict amyloid independent cognitive decline in aging.

Introduction: Amyloid beta (Aβ) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD).

Methods: We investigated relationships between concurrent longitudinal measures of Aβ (Pittsburgh compound B [PiB] positron emission tomography [PET]), tau (flortaucipir [FTP] PET), atrophy (structural magnetic resonance imaging), episodic memory (EM), and non-memory (NM) in 78 cognitively healthy older adults (OA).

Results: Entorhinal FTP change was correlated with EM decline regardless of Aβ, but meta-temporal FTP and global PiB change were only associated with EM and NM decline in Aβ+ OA.

Evaluation of Plasma Phosphorylated Tau217 for Differentiation Between Alzheimer Disease and Frontotemporal Lobar Degeneration Subtypes Among Patients With Corticobasal Syndrome.

Importance: Plasma phosphorylated tau217 (p-tau217), a biomarker of Alzheimer disease (AD), is of special interest in corticobasal syndrome (CBS) because autopsy studies have revealed AD is the driving neuropathology in up to 40% of cases. This differentiates CBS from other 4-repeat tauopathy (4RT)-associated syndromes, such as progressive supranuclear palsy Richardson syndrome (PSP-RS) and nonfluent primary progressive aphasia (nfvPPA), where underlying frontotemporal lobar degeneration (FTLD) is typically the primary neuropathology.

Objective: To validate plasma p-tau217 against positron emission tomography (PET) in 4RT-associated syndromes, especially CBS.

Regional Vulnerability of the Corpus Callosum in the Context of Cardiovascular Risk.

Many factors outside of cardiovascular health can impact the structure of white matter. Identification of reliable and clinically meaningful biomarkers of the neural effects of systemic and cardiovascular health are needed to refine etiologic predictions. We examined whether the corpus callosum demonstrates regional vulnerability to systemic cardiovascular risk factors.

Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors.

Aging is characterized by a progressive loss of brain volume at an estimated rate of 5% per decade after age 40. While these morphometric changes, especially those affecting gray matter and atrophy of the temporal lobe, are predictors of cognitive performance, the strong association with aging obscures the potential parallel, but more specific role, of individual subject physiology. Here, we studied a cohort of 554 human subjects who were monitored using structural MRI scans and blood immune protein concentrations.

Physical activity measurement in older adults: Wearables versus self-report.

Physical activity (PA) is associated with preserved age-related body and brain health. However, PA quantification can vary. Commercial-grade wearable monitors are objective, low burden tools to capture PA but are less well validated in older adults.

Combined Effects of Synaptic and Axonal Integrity on Longitudinal Gray Matter Atrophy in Cognitively Unimpaired Adults.

Background And Objectives: Synaptic dysfunction and degeneration is a predominant feature of brain aging, and synaptic preservation buffers against Alzheimer disease (AD) protein-related brain atrophy. We tested whether CSF synaptic protein concentrations similarly moderate the effects of axonal injury, indexed by CSF neurofilament light [NfL]), on brain atrophy in clinically normal adults.

Methods: Clinically normal older adults enrolled in the observational Hillblom Aging Network study at the UCSF Memory and Aging Center completed baseline lumbar puncture and longitudinal brain MRI (mean scan [follow-up] = 2.

Retinal arteriolar parameters as a surrogate marker of intracranial vascular pathology.

Introduction: Development of novel diagnostic tools is a top research priority in vascular dementia. A major obstacle is the lack of a simple, non-invasive method to visualize cerebral arteriolar walls in vivo. Retinal arterioles offer a window into the cerebral circulation.

Wearable Use in an Observational Study Among Older Adults: Adherence, Feasibility, and Effects of Clinicodemographic Factors.

Introduction: Wearables have great potential to improve monitoring and delivery of physical activity interventions to older adults with downstream benefits to multisystem health and longevity; however, benefits obtained from wearables depend on their uptake and usage. Few studies have examined person-specific factors that relate to wearable adherence. We characterized adherence to using a wearable activity tracker for 30 days and examined associations between adherence and demographics, cognitive functioning, brain volumes, and technology familiarity among community-dwelling older adults.

Multi-Modal Biomarkers of Repetitive Head Impacts and Traumatic Encephalopathy Syndrome: A Clinicopathological Case Series.

Traumatic encephalopathy syndrome (TES) criteria were developed to aid diagnosis of chronic traumatic encephalopathy (CTE) pathology during life. Interpreting clinical and biomarker findings in patients with TES during life necessitates autopsy-based determination of the neuropathological profile. We report a clinicopathological series of nine patients with previous repetitive head impacts (RHI) classified retrospectively using the recent TES research framework (100% male and white/Caucasian, age at death 49-84) who completed antemortem neuropsychological evaluations, T1-weighted magnetic resonance imaging, diffusion tensor imaging ( = 6), (18)F-fluorodeoxyglucose-positron emission tomography ( = 5), and plasma measurement of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau ( = 8).

Roles of physical activity and diet in cognitive aging: is more better?

To determine the synergistic effects of nutrition, specifically adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, and physical activity on cognition and brain outcomes in a cross-sectional healthy aging cohort. A total of 132 adults (age range 52-91; Clinical Dementia Rating = 0) from the UCSF Brain Aging Project completed a 15-item MIND diet food frequency questionnaire and an 11-item self-report measure of weekly physical activity (Physical Activity Scale [PASE]). Cognitive outcomes included executive functioning, episodic memory, and language.

Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study.

Background: Plasma tau phosphorylated at threonine 217 (p-tau217) and plasma tau phosphorylated at threonine 181 (p-tau181) are associated with Alzheimer's disease tau pathology. We compared the diagnostic value of both biomarkers in cognitively unimpaired participants and patients with a clinical diagnosis of mild cognitive impairment, Alzheimer's disease syndromes, or frontotemporal lobar degeneration (FTLD) syndromes.

Methods: In this retrospective multicohort diagnostic performance study, we analysed plasma samples, obtained from patients aged 18-99 years old who had been diagnosed with Alzheimer's disease syndromes (Alzheimer's disease dementia, logopenic variant primary progressive aphasia, or posterior cortical atrophy), FTLD syndromes (corticobasal syndrome, progressive supranuclear palsy, behavioural variant frontotemporal dementia, non-fluent variant primary progressive aphasia, or semantic variant primary progressive aphasia), or mild cognitive impairment; the participants were from the University of California San Francisco (UCSF) Memory and Aging Center, San Francisco, CA, USA, and the Advancing Research and Treatment for Frontotemporal Lobar Degeneration Consortium (ARTFL; 17 sites in the USA and two in Canada).

Lower White Matter Volume and Worse Executive Functioning Reflected in Higher Levels of Plasma GFAP among Older Adults with and Without Cognitive Impairment.

Objective: There are minimal data directly comparing plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in aging and neurodegenerative disease research. We evaluated associations of plasma NfL and plasma GFAP with brain volume and cognition in two independent cohorts of older adults diagnosed as clinically normal (CN), mild cognitive impairment (MCI), or Alzheimer's dementia.

Methods: We studied 121 total participants (Cohort 1: = 50, age 71.

Interbatch Reliability of Blood-Based Cytokine and Chemokine Measurements in Community-Dwelling Older Adults: A Cross-Sectional Study.

Blood-based inflammatory markers hold considerable promise for diagnosis and prognostication of age-related neurodegenerative disease, though a paucity of research has empirically tested how reliably they can be measured across different experimental runs ("batches"). We quantified the interbatch reliability of 13 cytokines and chemokines in a cross-sectional study of 92 community-dwelling older adults (mean age = 74; 48% female). Plasma aliquots from the same blood draw were parallelly processed in 2 separate batches using the same analytic platform and procedures (high-performance electrochemiluminescence by Meso Scale Discovery).

Wisdom and fluid intelligence are dissociable in healthy older adults.

Objectives: The relationship between wisdom and fluid intelligence (Gf) is poorly understood, particularly in older adults. We empirically tested the magnitude of the correlation between wisdom and Gf to help determine the extent of overlap between these two constructs.

Design: Cross-sectional study with preregistered hypotheses and well-powered analytic plan (https://osf.

Tripartite Relationship Among Synaptic, Amyloid, and Tau Proteins: An In Vivo and Postmortem Study.

Objective: To test the hypothesis that fundamental relationships along the amyloid, tau, and neurodegeneration (A/T/N) cascade depend on synaptic integrity in older adults in vivo and postmortem.

Methods: The 2 independent observational, cross-sectional cohorts included (1) in vivo community-dwelling, clinically normal adults from the University of California, San Francisco Memory and Aging Center who completed lumbar puncture and MRI (exclusion criteria, Clinical Dementia Rating score >0) and (2) postmortem decedents from the Rush Memory and Aging Project (exclusion criteria, inability to sign informed consent). In vivo measures included CSF synaptic proteins (synaptotagmin-1, synaptosome associated protein-25, neurogranin, and growth associated protein-43), β-amyloid (Aβ), tau phosphorylated at amino acid 181 (ptau), and MRI gray matter volume (GMV).

APOE moderates the effect of hippocampal blood flow on memory pattern separation in clinically normal older adults.

Pattern separation, the ability to differentiate new information from previously experienced similar information, is highly sensitive to hippocampal structure and function and declines with age. Functional MRI studies have demonstrated hippocampal hyperactivation in older adults compared to young, with greater task-related activation associated with worse pattern separation performance. The current study was designed to determine whether pattern separation was sensitive to differences in task-free hippocampal cerebral blood flow (CBF) in 130 functionally intact older adults.

Association of remote mild traumatic brain injury with cortical amyloid burden in clinically normal older adults.

We investigated whether clinically normal older adults with remote, mild traumatic brain injury (mTBI) show evidence of higher cortical Aβ burden. Our study included 134 clinically normal older adults (age 74.1 ± 6.

Development and validation of the Uniform Data Set (v3.0) executive function composite score (UDS3-EF).

Introduction: Cognitive composite scores offer a means of precisely measuring executive functioning (EF).

Methods: We developed the Uniform Data Set v3.0 EF composite score (UDS3-EF) in 3507 controls from the National Alzheimer's Coordinating Center dataset using item-response theory and applied nonlinear and linear demographic adjustments.

Worth the Wait: Delayed Recall after 1 Week Predicts Cognitive and Medial Temporal Lobe Trajectories in Older Adults.

Method: Clinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.

Aging and Positive Mood: Longitudinal Neurobiological and Cognitive Correlates.

Objective: Despite the losses commonly associated with aging, older adults seem to possess particularly preserved emotional regulation. To further understand this phenomenon, the authors examined longitudinal trajectories between age, depressive symptoms, brain structure, and cognition.

Methods: Seven hundred and sixteen functionally intact older adults (age M = 67.