Clinical Manifestations.

Background: The multisite SuperAging Research Initiative (SRI) was established in 2021 to identify resilience and resistance factors promoting cognitive healthspan through a harmonized multidisciplinary protocol with prospective data collection. The designation of SuperAger is reserved for individuals age 80+ with episodic memory performance that is at least average for those 2-3 decades younger. Research studies of this relatively uncommon phenotype allow for investigations of fundamental importance to the neurobiology of brain aging, resilience, resistance, and avoidance of cognitive decline related to "average aging" and more severe impairments associated with Alzheimer's and related dementias (ADRD).

Assessment of disease impact through health-related quality of life measurement in primary progressive aphasia.

Introduction: Measurements of health-related quality of life (HRQoL) are important for capturing disease impact beyond physical health and relative to other diseases but have rarely been assessed in primary progressive aphasia (PPA).

Methods: HRQoL was characterized overall, by sex and subtype in PPA ( = 118) using the Health Utilities Index-2/3 (HUI2/3). Multiple linear regression assessed associations between HRQoL and language severity.

Distinct Patterns of Hippocampal Pathology in Alzheimer's Disease with Transactive Response DNA-binding Protein 43.

Objective: Age-related dementia syndromes are often not related to a single pathophysiological process, leading to multiple neuropathologies found at autopsy. An amnestic dementia syndrome can be associated with Alzheimer's disease (AD) with comorbid transactive response DNA-binding protein 43 (TDP-43) pathology (AD/TDP). Here, we investigated neuronal integrity and pathological burden of TDP-43 and tau, along the well-charted trisynaptic hippocampal circuit (dentate gyrus [DG], CA3, and CA1) in participants with amnestic dementia due to AD/TDP, amnestic dementia due to AD alone, or non-amnestic dementia due to TDP-43 proteinopathy associated with frontotemporal lobar degeneration (FTLD-TDP).

Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies.

Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy.

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States.

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots.

Fast estimation of mixed-effects location-scale regression models.

As a result of advances in data collection technology and study design, modern longitudinal datasets can be much larger than they historically have been. Such "intensive" longitudinal datasets are rich enough to allow for detailed modeling of the variance of a response as well as the mean, and a flexible class of models called mixed-effects location-scale (MELS) regression models are commonly used to do so. However, fitting MELS models can pose computational challenges related to the numerical evaluation of multi-dimensional integrals; the slow runtime of current methods is inconvenient for data analysis and makes bootstrap inference impractical.

Differential vulnerability of the dentate gyrus to tauopathies in dementias.

The dentate gyrus (DG), a key hippocampal subregion in memory processing, generally resists phosphorylated tau accumulation in the amnestic dementia of the Alzheimer's type due to Alzheimer's disease (DAT-AD), but less is known about the susceptibility of the DG to other tauopathies. Here, we report stereologic densities of total DG neurons and tau inclusions in thirty-two brains of human participants with autopsy-confirmed tauopathies with distinct isoform profiles-3R Pick's disease (PiD, N = 8), 4R corticobasal degeneration (CBD, N = 8), 4R progressive supranuclear palsy (PSP, N = 8), and 3/4R AD (N = 8). All participants were diagnosed during life with primary progressive aphasia (PPA), an aphasic clinical dementia syndrome characterized by progressive deterioration of language abilities with spared non-language cognitive abilities in early stages, except for five patients with DAT-AD as a comparison group.

Integrity of Neuronal Size in the Entorhinal Cortex Is a Biological Substrate of Exceptional Cognitive Aging.

Average aging is associated with a gradual decline of memory capacity. SuperAgers are humans ≥80 years of age who show exceptional episodic memory at least as good as individuals 20-30 years their junior. This study investigated whether neuronal integrity in the entorhinal cortex (ERC), an area critical for memory and selectively vulnerable to neurofibrillary degeneration, differentiated SuperAgers from cognitively healthy younger individuals, cognitively average peers ("Normal Elderly"), and individuals with amnestic mild cognitive impairment.

Geometric deep learning reveals a structuro-temporal understanding of healthy and pathologic brain aging.

Background: Brain age has historically been investigated primarily at the whole brain level. The ability to deconstruct the brain into its composite parts and explore brain age at the sub-structure level offers unique advantages. These include the exploration of dynamic and interconnected relationships between different brain structures in healthy and pathologic aging.

Eye movements as a measure of word comprehension deficits in primary progressive aphasia.

Introduction: Eye movement studies can uncover subtle aspects of language processing impairment in individuals with primary progressive aphasia (PPA), who may have difficulty understanding words. This study examined eye movement patterns on a word-object matching task in response to varying levels of word-knowledge in PPA.

Methods: Participants with semantic and non-semantic PPA completed an object-matching task, where a word was presented and participants then selected the corresponding pictured object from an array.

Neuropathological fingerprints of survival, atrophy and language in primary progressive aphasia.

Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer's disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick's disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.

Path-level interpretation of Gaussian graphical models using the pair-path subscore.

BACKGROUND : Construction of networks from cross-sectional biological data is increasingly common. Many recent methods have been based on Gaussian graphical modeling, and prioritize estimation of conditional pairwise dependencies among nodes in the network. However, challenges remain on how specific paths through the resultant network contribute to overall 'network-level' correlations.

The propagule doesn't fall far from the tree, especially after short-interval, high-severity fire.

Subalpine forests that historically burned every 100-300 yr are expected to burn more frequently as climate warms, perhaps before trees reach reproductive maturity or produce a serotinous seedbank. Tree regeneration after short-interval (<30-yr) high-severity fire will increasingly rely on seed dispersal from unburned trees, but how dispersal varies with age and structure of surrounding forest is poorly understood. We studied wind dispersal of three conifers (Picea engelmannii, Abies lasiocarpa, and Pinus contorta var.

Remote allergen exposure elicits eosinophil infiltration into allergen nonexposed mucosal organs and primes for allergic inflammation.

The natural history of allergic diseases suggests bidirectional and progressive relationships between allergic disorders of the skin, lung, and gut indicative of mucosal organ crosstalk. However, impacts of local allergic inflammation on the cellular landscape of remote mucosal organs along the skin:lung:gut axis are not yet known. Eosinophils are tissue-dwelling innate immune leukocytes associated with allergic diseases.

Invasive rat control is an efficient, yet insufficient, method for recovery of the critically endangered Hawaiian plant hau kuahiwi (Hibiscadelphus giffardianus).

Biological invasions of rodents and other species have been especially problematic on tropical islands. Invasive Rattus rattus consumption of Hibiscadelphus giffardianus (Malvaceae; common Hawaiian name hau kuahiwi) fruit and seeds has been hypothesized to be the most-limiting factor inhibiting the critically endangered tree, but this has not been experimentally tested, and little is known about other factors affecting seed dispersal, germination, and seedling establishment. Thus, we do not know if rat removal is sufficient to increase hau kuahiwi recruitment.