Cognitive deficit, and neuropathological correlates, in the oldest-old

Area of Science:

• Neurology
• Geriatrics
• Pathology

Background:

• Cognitive decline in the oldest old is multifactorial, not solely attributable to Alzheimer's disease.
• Vascular changes, TDP-43 proteinopathies (Limbic-predominant Age-related TDP-43 Encephalopathy - LATE), Lewy bodies, and tau inclusions are increasingly recognized contributors.
• Systemic conditions and external factors can also exacerbate cognitive impairment.

Purpose of the Study:

• To review the diverse pathological underpinnings of cognitive deficits in the oldest old.
• To emphasize the importance of considering multiple diagnoses beyond Alzheimer's disease.
• To highlight associated conditions and potential therapeutic targets.

Main Methods:

• Review of existing literature on neurodegenerative and vascular pathologies in the elderly.
• Analysis of clinical presentations and neuropathological findings.
• Discussion of diagnostic criteria and differential diagnoses.

Main Results:

• Alzheimer's disease, while common, is often associated with vascular alterations and other neurodegenerative pathologies.
• Hippocampal sclerosis and Limbic-predominant Age-related TDP-43 Encephalopathy (LATE) are significant causes of memory loss, especially with negative Alzheimer's biomarkers.
• Cortical Lewy bodies and tau inclusions also contribute to cognitive impairment.

Conclusions:

• Cognitive impairment in the oldest old frequently results from a combination of neurodegenerative and vascular pathologies.
• Accurate diagnosis requires consideration of multiple potential causes, including LATE and Lewy body disease.
• Identifying and treating contributing systemic diseases and toxic factors is essential for managing cognitive decline.