Effects of Risperidone and Galantamine Treatment on Alzheimer’s Disease Biomarker Levels in Cerebrospinal Fluid

Abstract

Background Treatment for neuropsychiatric symptoms (NPS) in dementia is insufficient. Antipsychotics and acetylcholinesterase inhibitors are used generating symptomatic improvements in behaviour and cognition, but few studies have investigated their effect on Alzheimer biomarkers in cerebrospinal fluid (CSF). Aim This is a secondary analysis based on an earlier clinical trial comparing the treatment effects on NPS. The aim of this study was to examine whether treatment with risperidone and galantamine affect levels of biomarkers T-Tau, P-Tau, Aβ1–42, and Aβ40/42-ratio in CSF. The secondary aim was to test if baseline levels of these biomarkers are associated with the clinical course of NPS. Methods 83 patients (mean + SD 77.9.6±7.7 years) with dementia and NPS were randomized to galantamine (n=44) or risperidone (n=39) treatment. CSF samples were collected at baseline and after 12 weeks. Results Changes in levels of biomarkers between the two treatment groups did not differ significantly. Low baseline levels of Aβ1–42 was significantly associated with reduction of irritability at follow up. Low baseline levels of Aβ1–42, Aβ42/40 and P-Tau were significant correlates of reduction in appetite and eating disorders. CSF Aβ1–42 levels in patients treated with risperidone were significantly decreased at follow up, showing a 8% (40 pg/mL) reduction as compared with baseline (p=0.03). Conclusions Our results suggest that risperidone may affect the CSF profile of AD biomarkers indicating more amyloid pathology. Treatment with galantamine did not affect the CSF biomarkers in any direction. The Alzheimer CSF biomarkers displayed correlations with specific NPS suggesting potential research questions to be pursued.

Acorenone B: AChE and BChE Inhibitor as a Major Compound of the Essential Oil Distilled from the Ecuadorian Species Niphogeton dissecta (Benth.) J.F. Macbr

“…These inhibitory potentials, even far from that of the reference compound donepezil (6.7 nM) versus AChE [ 38 ], are close to those previously published for galanthamine (2.2 µg/mL and 11.7 µg/mL) or other plant extracts [ 4 , 39 , 40 ]. Interestingly, in spite of its moderate inhibitory potential, galanthamine is a typical drug used for the treatment of Alzheimer's disease [ 41 ], validating our efforts to identify new potential inhibitory compounds. Niphogeton dissecta essential oil exhibited selectivity for the inhibition of BChE, this property being particularly interesting in the treatment of Alzheimer's disease [ 40 , 42 ].…”

Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

“…Bloniecki et al. found that in a cohort of subjects with AD and NPS agitation measured with the Cohen‐Mansfield Agitation Inventory (CMAI) correlated with total‐tau (r = 0.36, P = .04) and phosphorylated‐tau r = 0.35, P = .05) in AD patients, indicating that tau‐mediated pathology including neurofibrillary tangles and the disease intensity might be associated with agitation in AD 156,157 . In their systematic review of CSF correlates of NPS in AD and aMCI, Showraki et al.…”

Insights into the Molecular Mechanisms of Alzheimer’s and Parkinson’s Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology

“…Side effects include nausea, vomiting, loss of appetite and increased frequency of bowel movements. Among three cholinesterase inhibitors that are commonly prescribed, Aricept is approved to treat all stages of AD whereas Exelon and Razadyne are approved to treat mild to moderate AD [ 134 , 135 , 136 ]. Memantine regulates the activity of glutamate, which is a chemical involved in information processing, storage and retrieval [ 137 ].…”