Effects of nicergoline treatment on regional cerebral blood flow in early Alzheimer's disease

Abstract

Alzheimer's disease (AD) is associated with reduction of regional cerebral blood flow (rCBF) in various brain regions. Although nicergoline has been used to treat cognitive impairment in various types of dementia, the effect of nicergoline on brain perfusion in AD has not been elucidated. The aim of the study was to examine the effect of nicergoline on rCBF in patients with early AD using technetium‐99m hexamethylpropylene amine oxime single‐photon emission computed tomography (SPECT). For 1.7 years on average, 22 patients with early AD received nicergoline (30 mg twice daily) and acetylcholinesterase inhibitors (AChEI), whereas other 22 patients received AChEI only. All patients underwent assessment of dementia severity and SPECT scans at baseline and follow‐up. We compared baseline rCBF and annual percent change of rCBF between the two groups. There were no significant differences in rCBF between the groups at baseline. Although changes in dementia severity was not statistically different, the annual percent changes of rCBF were higher in the left temporal pole (−0.12 ± 3.95 vs −3.38 ± 3.30, P = 0.002) and middle cingulate gyrus (1.91 ± 3.58 vs −1.34 ± 3.17, P = 0.002) among the nicergoline group. Our study demonstrated that nicergoline treatment combined with AChEI either better preserves or further improves cerebral perfusion in the temporal and cingulate cortices in patients with early AD compared to AChEI treatment alone. These results may indicate potential beneficial effects of nicergoline on brain functions in AD.

Phosphodiesterase Inhibitors for Alzheimer’s Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale

“…Clinical trials of PF-04447943 and BI 409,306 have shown a lack of efficacy [341,342], which might be because PDE9 inhibition increases periplasma membrane cGMP (rather than cytoplasmic cGMP) and allows Ca 2+ influx through CNG [68,71,213]. The clinical trials of vinpocetine [253,[255][256][257][258], cilostazol [69,[317][318][319], and nicergoline are preliminary and mixed [273][274][275][276][277], with cilostazol and nicergoline likely being the most promising and the worthiest of further study of these three [273][274][275][276][277]. Deprenyl/selegiline clinical trials show short-term but not long-term benefits, making deprenyl somewhat disappointing [289].…”

“…No statistically significant differences were noted in the severity of dementia, activities of daily living, cognition, and depressive symptoms between baseline and follow-up. However, nicergoline increased cerebral blood flow in frontal and parietal regions [276].A 2019 study in 22 patients with early AD found that, compared to acetylcholine esterase inhibitors alone, acetylcholine esterase inhibitors plus nicergoline preserved cerebral blood flow to the left temporal pole and the middle cingulate gyrus but did not result in any significant difference in dementia severity [277].…”

“…There are mixed reports about whether the improvement on the ADAS-Cog at 6 months that nicergoline provided was significant, and there was a non-significant trend toward slower cognitive decline on this scale at 12 months [273][274][275]. However, two more recent pilot trials had disappointing results [276,277]. This makes it inconclusive whether nicergoline is useful for the treatment of AD.…”

“…Nicergoline PDE1 and cGMP-stimulated PDE2 [259] May be effective for the treatment of dementia [273]. Inconclusive whether effective for the treatment of AD [273][274][275][276][277]. Deprenyl/selegiline PDE1A2 [224,279] Only short-term improvements in AD [289].…”

Range and variability of CBF in young adults: PC‐MRI and ASL studies

“…Quantitative CBF serves as a valuable metric for monitoring pathophysiological changes in cerebrovascular function and brain metabolism. Moreover, numerous conditions are associated with alterations in CBF, including cognitive decline, 1 white matter hyperintensity, 2 and Alzheimer's disease 3 . To gain a better understanding of potential changes in brain perfusion across various conditions, it is essential to establish normal reference values and acknowledge intersubject variations.…”