Alzheimer's disease with normal CSF biomarkers.

Abstract

Background/objectives: Alzheimer’s disease (AD) is currently diagnosed clinically using defined symptomatic diagnostic criteria. Pathological levels of CSF-biomarkers, high T-tau, P-tau and low Ab42 have been associated with AD however definition of cut off values differ. New diagnostic criteria that include the pathological CSF biomarkers have been suggested. How many AD patients in a routine clinical population have normal levels of the CSF biomarkers as defined by clinically defined cut-offs? Methods: Out-patients (n=151) with the clinical diagnosis of dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) and probable or possible AD, according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and related Disorders Association (NINCDS-ADRDA, 1984), were included in this study. The number of symptoms according to these criteria and the levels of the CSF biomarkers Aβ42, T-tau and P-tau were evaluated at baseline. The patients received cholinesterase inhibitor (ChEI) treatment and were assessed with cognitive tests (MMSE, ADAS-cog) longitudinally for up to three years. Short-term ChEI-response was measured as cognitive change after 2 and 6 months of treatment. Long-term outcome was expressed as MMSE and ADAS-cog change per month. Pathological levels of CSF biomarkers were defined as in clinical routine; T-tau > 450 ng/l, P-tau > 60 ng/l and aβ42 < 400 ng/l. Results: In 15 % of the patients all three CSF biomarkers were normal. At baseline these patients had fewer symptoms (NINCDS-ADRDA), higher MMSE score, but then displayed the same rate of longitudinal cognitive decline as patients with pathological biomarkers. Furthermore, patients with normal CSF biomarkers did not differ in age of onset, duration of disease, IADL or ADAS-cog at baseline, completion rate or short-term response to treatment compared to those with pathological CSF biomarkers. Conclusion: Alzheimer’s disease with normal CSF displays the same cognitive short-term response to ChEI-treatment and clinical long-term outcome as patients with pathological CSF. These findings must be considered when defining future diagnostic criteria for AD. (Less)