Early onset dementia : clinical utility of cerebrospinal fluid amyloidbeta and tau measures in diagnosing mild cognitive impairment

Abstract

Background: The differentiation of a preclinical or prodromal Alzheimer's disease (AD) is challenging particularly in patients with Early Onset Alzheimer's or Related Dementias (EOARD). The first clinical symptoms of AD during the prodromal phase are mild cognitive impairment (MCI), with some younger adults presenting with depression or anxiety. We report a local practice on utilising diagnostic lumbar puncture to investigate the cause of MCI for the diagnosis of EOARD at a tertiary neurocognitive referral centre. Method(s): The study was approved by the Ethic Committee (Ref:18/EM/0292). 30 participants aged 32-68 years old at the onset of symptoms (mean 62 years; 61% female) from the Nottingham EOARD clinics (UK) were included. Clinical diagnosis was based on clinical presentation, neurocognitive profile, radiological features (MRI, FDG-PET CT) and CSF amyloidbeta1-42/1-40 (Abeta), total tau and Thr181-phosphorylated tau measurements. Patients were classified into three groups according to the clinical diagnosis: a)MCI secondary to Alzheimer's disease as defined by NIA-AA Research Framework [n=16]. b)Subjective Cognitive impairment, stable impairment in cognitive battery with no evidence of neurodegeneration on neuroimaging or abnormal levels of Amyloidb/tau in the CSF [n=9]. c)Other neurodegenerative conditions [n=5] (Table). Result(s): In patients with MCI, the CSF total tau and Thr181-phosphorylated tau levels showed a non-linear relationship with age, with an inverse U-shaped curve reaching the highest level at the age of 55 years, followed by a significant decline in the following decade (Figure). In contrast, the CSF Abeta level decreased in the MCI group, independently of age, and was associated with the neuropsychological measures of memory impairment (p=0.037). In contrast, total and phosphorylated CSF tau levels did not correlate with the cognitive performance measures. Similarly, the principal component analysis confirmed that the clinical diagnosis of Alzheimer's MCI (as per the NIA-AA criteria) correlated with the CSF Abeta loss. Conclusion(s): In Early Onset Alzheimer's disease, the low levels of CSF Abeta appear to be more sensitive than the total and 181Thr-phosphorylated tau measures in differentiating Alzheimer's MCI from other forms of dementia. Further work on larger samples of EOARD in clinical practice will address the cost effectiveness due to making an earlier diagnosis.