Deep learning assisted quantitative analysis of Aβ and microglia in patients with idiopathic normal pressure hydrocephalus in relation to cognitive outcome

Neuropathologic changes of Alzheimer disease (AD) including Aβ accumulation and neuroinflammation are frequently observed in the cerebral cortex of patients with idiopathic normal pressure hydrocephalus (iNPH). We created an automated analysis platform to quantify Aβ load and reactive microglia in the vicinity of Aβ plaques and to evaluate their association with cognitive outcome in cortical biopsies of patients with iNPH obtained at the time of shunting. Aiforia Create deep learning software was used on whole slide images of Iba1/4G8 double immunostained frontal cortical biopsies of 120 shunted iNPH patients to identify Iba1-positive microglia somas and Aβ areas, respectively. Dementia, AD clinical syndrome (ACS), and Clinical Dementia Rating Global score (CDR-GS) were evaluated retrospectively after a median follow-up of 4.4 years. Deep learning artificial intelligence yielded excellent (>95%) precision for tissue, Aβ, and microglia somas. Using an age-adjusted model, higher Aβ coverage predicted the development of dementia, the diagnosis of ACS, and more severe memory impairment by CDR-GS whereas measured microglial densities and Aβ-related microglia did not correlate with cognitive outcome in these patients. Therefore, cognitive outcome seems to be hampered by higher Aβ coverage in cortical biopsies in shunted iNPH patients but is not correlated with densities of surrounding microglia.