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[O4–03–01]: MAINTENANCE OF COGNITIVE IMPROVEMENT TREATMENT RESPONSE WITH MEMANTINE AND DONEPEZIL: POST HOC ANALYSES FROM A PLACEBO‐CONTROLLED STUDY IN PATIENTS WITH MODERATE TO SEVERE ALZHEIMER's DISEASE
Author(s) -
Atri Alireza,
Cummings Jeffrey L.,
Hendrix Suzanne,
Ellison Noel,
Andersen Kristen A.,
Edwards John
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.07.430
Subject(s) - donepezil , memantine , placebo , post hoc analysis , medicine , clinical endpoint , psychology , anesthesia , randomized controlled trial , dementia , disease , pathology , alternative medicine
transgenic mice, NPTX2 knockout and A-beta amyloidosis synergistically disrupted hippocampal rhythmicity and GluA4 expression. Measured by Western blot and a specific ELISA, levels of NPTX2 were decreased in human CSF in AD and MCI vs agematched controls, replicated in two cohorts. Across MCI and AD, CSF levels of NPTX2 correlated with the Mattis DRS, an overall test of cognition and with measures of hippocampal volume to a greater extent than did other CSF biomarkers including A-beta42, tau or P-tau181. NPTX2 did not correlate with Aß or tau in human or mouse indicating that it represents an independent parameter. Conclusions: NPTX2 down-regulation is an important part of AD pathogenesis that alters synaptic homeostatic regulation and is closely linked to cognitive deterioration. CSF levels of NPTX2 have diagnostic value and correlate with cognition in AD.