Contributions of Vascular Burden and Amyloid Abnormality to Cognitive Decline in Memory Clinic Patients
Veerle van Gils1, Inez Ramakers1,2, Willemijn J Jansen1
1Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands.
Insights
Alzheimer's disease amyloid pathology predicts cognitive decline independently of vascular burden in memory clinic patients. Vascular burden plays a minor role in cognitive decline for this population.
Area of Science:
- Neurology
- Neuroscience
- Geriatrics
Background:
- Alzheimer's disease (AD) pathology and cerebrovascular burden frequently coexist in older adults.
- The interplay between AD pathology, vascular burden, and cognitive decline remains incompletely understood.
Purpose of the Study:
- To determine if amyloid abnormality and vascular burden synergistically impact cognitive decline in a memory clinic cohort.
- To investigate the independent and combined effects of amyloid and vascular pathology on cognitive trajectories.
Main Methods:
- 227 memory clinic patients were analyzed for amyloid abnormality (A+) via CSF Aβ42 and vascular burden (V+) using MRI-defined white matter hyperintensities, microbleeds, macrohemorrhage, or infarcts.
- Longitudinal cognitive changes (global cognition, memory, processing speed, executive function, verbal fluency) were assessed across four groups (A-V-, A-V+, A+V-, A+V+) using linear mixed models.
- Alternative definitions for vascular burden, including individual MRI measures and vascular risk factors, were explored.
Main Results:
- At baseline, the amyloid-positive, vascular-positive (A+V+) group exhibited poorer global cognition and verbal fluency than other groups.
- Over a mean follow-up of 2.7 years, both A+V+ and amyloid-positive, vascular-negative (A+V-) groups showed accelerated global cognitive decline compared to amyloid-negative groups.
- Amyloid abnormality (A+) independently predicted global cognitive decline, while vascular burden showed a limited independent association, primarily with executive function decline via microbleeds.
Conclusions:
- Amyloid abnormality is a significant predictor of cognitive decline in memory clinic patients, irrespective of vascular burden.
- Vascular burden contributes minimally to cognitive decline in this population, suggesting amyloid pathology is the primary driver.
- These findings have crucial prognostic implications for understanding and managing cognitive decline in aging populations.
Background:
Alzheimer's disease pathology and vascular burden are highly prevalent and often co-occur in elderly. It remains unclear how both relate to cognitive decline.
Objective:
To investigate whether amyloid abnormality and vascular burden synergistically contribute to cognitive decline in a memory clinic population.
Methods:
We included 227 patients from Maastricht and Aachen memory clinics. Amyloid abnormality (A+) was defined by CSF Aβ42 using data-driven cut-offs. Vascular burden (V+) was defined as having moderate to severe white matter hyperintensities, or any microbleeds, macrohemorrhage or infarcts on MRI. Longitudinal change in global cognition, memory, processing speed, executive functioning, and verbal fluency was analysed across the A-V-, A-V+, A+V-, A+V+ groups by linear mixed models. Additionally, individual MRI measures, vascular risk and vascular disease were used as V definitions.
Results:
At baseline, the A+V+ group scored worse on global cognition and verbal fluency compared to all other groups, and showed worse memory compared to A-V+ and A-V- groups. Over time (mean 2.7+ - 1.5 years), A+V+ and A+V- groups showed faster global cognition decline than A-V+ and A-V- groups. Only the A+V- group showed decline on memory and verbal fluency. The A-V+ group did not differ from the A-V- group. Individual MRI vascular measures only indicated an independent association of microbleeds with executive functioning decline. Findings were similar using other V definitions.
Conclusions:
Our study demonstrates that amyloid abnormality predicts cognitive decline independent from vascular burden in a memory clinic population. Vascular burden shows a minor contribution to cognitive decline in these patients. This has important prognostic implications.
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