Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Ajay Kumar Nair; Carol A Van Hulle; Barbara B Bendlin; Henrik Zetterberg; Kaj Blennow; Norbert Wild; Gwendlyn Kollmorgen; Ivonne Suridjan; William W Busse; Melissa A Rosenkranz

doi:10.1002/trc2.12315

Asthma amplifies dementia risk: Evidence from CSF biomarkers and cognitive decline

Alzheimers Dement (N Y). 2022 Jul 8;8(1):e12315. doi: 10.1002/trc2.12315. eCollection 2022.

Authors

Ajay Kumar Nair¹, Carol A Van Hulle^{2

3}, Barbara B Bendlin^{2

3

4}, Henrik Zetterberg^{5

6

7

8

9}, Kaj Blennow^{5

6}, Norbert Wild¹⁰, Gwendlyn Kollmorgen¹⁰, Ivonne Suridjan¹¹, William W Busse³, Melissa A Rosenkranz^{1

12}

Affiliations

¹ Center for Healthy Minds University of Wisconsin-Madison Madison Wisconsin USA.
² Wisconsin Alzheimer's Disease Research Center School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
³ Department of Medicine School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
⁴ Wisconsin Alzheimer's Institute School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
⁵ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at The University of Gothenburg Mölndal Sweden.
⁶ Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden.
⁷ Department of Neurodegenerative Disease UCL Institute of Neurology London UK.
⁸ UK Dementia Research Institute at UCL London UK.
⁹ Hong Kong Center for Neurodegenerative Diseases Hong Kong People's Republic of China.
¹⁰ Roche Diagnostics GmbH Penzberg Germany.
¹¹ Roche Diagnostics International Ltd. Rotkreuz Switzerland.
¹² Department of Psychiatry University of Wisconsin-Madison Madison Wisconsin USA.

Abstract

Introduction: Evidence from epidemiology, neuroimaging, and animal models indicates that asthma adversely affects the brain, but the nature and extent of neuropathophysiological impact remain unclear.

Methods: We tested the hypothesis that asthma is a risk factor for dementia by comparing cognitive performance and cerebrospinal fluid biomarkers of glial activation/neuroinflammation, neurodegeneration, and Alzheimer's disease (AD) pathology in 60 participants with asthma to 315 non-asthma age-matched control participants (45-93 years), in a sample enriched for AD risk.

Results: Participants with severe asthma had higher neurogranin concentrations compared to controls and those with mild asthma. Positive relationships between cardiovascular risk and concentrations of neurogranin and α-synuclein were amplified in severe asthma. Severe asthma also amplified the deleterious associations that apolipoprotein E ε4 carrier status, cardiovascular risk, and phosphorylated tau₁₈₁/amyloid beta₄₂ have with rate of cognitive decline.

Discussion: Our data suggest that severe asthma is associated with synaptic degeneration and may compound risk for dementia posed by cardiovascular disease and genetic predisposition.

Highlights: Those with severe asthma showed evidence of higher dementia risk than controls evidenced by: higher levels of the synaptic degeneration biomarker neurogranin regardless of cognitive status, cardiovascular or genetic risk, and controlling for demographics.steeper increase in levels of synaptic degeneration biomarkers neurogranin and α-synuclein with increasing cardiovascular risk.accelerated cognitive decline with higher cardiovascular risk, genetic predisposition, or pathological tau.

Keywords: Alzheimer's disease; asthma; cerebrospinal fluid biomarkers; cognition; comorbidities; dementia; glial activation; neurodegeneration; neuroinflammation; synaptic dysfunction cognition.

Abstract

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