Sustained administration of PDE5 inhibitors improves memory, induces neuroplasticity and may reverse AD related histopathology in several transgenic mouse models of AD. Previous work involving the cohort of patients used in the present analysis has shown that sildenafil increases cerebral blood flow, particularly in the bilateral medial temporal lobes, at the expense of cerebrovascular reactivity, as well as increasing brain oxygen utilization. Here, we examine the fractional amplitude of low frequency fluctuations (fALFF) in the resting state fMRI BOLD signal (0.01 - 0.10 Hz) also collected before and after a single dose of sildenafil. Previous studies have demonstrated increased fALFF in hippocampi as well as parahippocampal gyri in patients with AD, so in this study we looked for evidence of reversal of such changes following sildenafil administration.

To analyze implications of alterations in the fractional amplitude of low frequency fluctuations (fALFF) in patients with Alzheimer’s disease (AD) after dosing with sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor.

We analyzed fALFF from 5 male and 5 female Caucasian participants with AD (MoCA average 18.2) before and after sildenafil administration to assess differences. Participants served as their own comparators.  

A significant decrease (p < 0.03) in fALFF was observed in the right hippocampus an hour after administration of 50 mg of sildenafil. Trend towards decrease was also observed in left parahippocampal gyrus, p = 0.08. 

Decreased fALFF in the hippocampus after acute sildenafil administration may represent a normalization of fALFF values in patients with AD. These data support the need for further investigation into the clinical effects of longer term sildenafil administration in patients with AD, extending previous basic science work.