Related Experiment Video

Updated: Oct 27, 2026

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains

Abbiategrasso Brain Bank Protocol for Collecting, Processing and Characterizing Aging Brains

Published on: June 3, 2020

Neuropathologic features of cognitively defined Alzheimer's disease subgroups in the Adult Changes in Thought study

Caitlin S Latimer¹, Rod L Walker², Marika Bogdani¹

¹Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association

|October 26, 2026

Abstract

Background:

Individuals with Alzheimer's disease (AD) dementia can be subgrouped based on cognitive performance at diagnosis. We compared neuropathology across cognitively defined AD subgroups in the Adult Changes in Thought study.

Methods:

Scores for memory, executive functioning, language, and visuospatial abilities were derived from the Cognitive Abilities Screening Instrument and a neurocognitive battery. Subgroups were defined by relative performance within domains. Standardized neuropathologic evaluation was performed post mortem. Associations were estimated using ordinal logistic regression, with odds ratios (OR) and 95% confidence intervals (CIs) comparing neuropathology between the AD subgroups and relative to individuals without dementia.

Results:

Of 885 participants with post mortem neuropathology, 370 had AD dementia: 54% AD-no domain, 15% AD-memory, 15% AD-visuospatial, 8% AD-language, and 7% AD-executive. Among AD subgroups, associations were detected for limbic-predominant age-related transactive response DNA binding protein 43 kDa encephalopathy neuropathologic change (LATE-NC; P = 0.019) and hippocampal sclerosis (HS; P = 0.006), with highest levels in AD-language (LATE-NC OR 2.37, 95% CI 1.03-5.46 and HS OR 2.19, 95% CI 0.88-5.50) and AD-memory (LATE-NC OR 1.88, 95% CI 1.02-3.46 and HS OR 3.11, 95% CI 1.56-6.20) relative to AD-no domain, and lowest levels in AD-visuospatial. AD-visuospatial tended to have lowest estimated Alzheimer's disease neuropathologic change (ADNC) burden across AD subgroups. Relative to participants without dementia, all AD subgroups expectedly had higher ADNC burden, and several AD subgroups had higher odds of Lewy body pathology (P = 0.017) and gross infarcts (P = 0.004), with broadly similar estimates across multiple AD subgroups.

Discussion:

Neuropathologic patterns of ADNC and co-pathologies across AD dementia subgroups suggest cognitive phenotyping may inform clinicopathologic studies of AD dementia.

Keywords:

Adult Changes in Thought study Alzheimer's disease cognitive subgroups neuropathology

More Related Videos

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans

Published on: December 18, 2016

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease

Published on: October 13, 2016

Related Concept Videos

Alzheimer Disease ll: Pathophysiology

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...

Alzheimer Disease l: Introduction

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...

Alzheimer's Disease: Overview

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...

Cognitive Development During Adulthood

Cognitive Development During Adulthood

Cognitive development continues throughout adulthood, undergoing significant shifts across early, middle, and late stages. Individual transition occurs from adolescent idealism to pragmatic and adaptable thinking in early adulthood. During this period, individuals learn to integrate personal beliefs with the recognition that other perspectives are equally valid. Exposure to the complexities of modern society, diverse experiences, and higher education contribute to this adaptive thought process,...

Dementia l: Introduction

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...

Cognitivism

Cognitivism

Cognitive psychology emerged as a significant field in the mid-20th century. It focused on understanding humans' internal mental processes. This approach emphasizes how people perceive, remember, think, and solve problems—elements critical to human cognition.
Previously dominated by behaviorism, which prioritized observable behaviors and largely ignored mental processes, psychology transformed in the 1950s. Cognitive psychologists argue that understanding how we think and process information is...

Articles linked to this work by shared authors, journal, and citation graph.

Single nucleus RNA sequencing and spatial transcriptomics reveal unique functionalities of gray matter versus white matter oligodendrocytes in aging and Alzheimer's Disease.

bioRxiv : the preprint server for biology·2026

Gantenerumab reduces brain amyloid-β proteoforms: Biochemical evaluation in dominantly inherited Alzheimer disease.

medRxiv : the preprint server for health sciences·2026

Alzheimer's disease neuropathological characterization of the dog brain and relationship to biofluid biomarkers and cognitive function.

NPJ dementia·2026

Association between a disease-specific frailty index and long-term quality of life outcomes in older adult patients with traumatic brain injury: a TRACK-TBI study.

GeroScience·2026

Aquaporin-4 mis-localization decreases glymphatic clearance of α-synuclein in an alpha-syntrophin knock out mouse model and promotes α-synuclein pathology and aggregate propagation.

Brain communications·2026

Somatic mutations reveal the ontogeny of microglia in human ageing.

Nature·2026

See all related articles