Alzheimer's Disease Diagnosis: Discrepancy between Clinical, Neuroimaging, and Cerebrospinal Fluid Biomarkers Criteria in an Italian Cohort of Geriatric Outpatients: A Retrospective Cross-sectional Study

Background: The role of cerebrospinal fluid (CSF) biomarkers, and neuroimaging in the diagnostic process of Alzheimer's disease (AD) is not clear, in particular in the older patients. Objective: The aim of this study was to compare the clinical diagnosis of AD with CSF biomarkers and with cerebrovascular damage at neuroimaging in a cohort of geriatric patients. Methods: Retrospective analysis of medical records of = 65-year-old patients with cognitive impairment referred to an Italian geriatric outpatient clinic, for whom the CSF concentration of amyloid-beta (A beta), total Tau (Tau), and phosphorylated Tau (p-Tau) was available. Clinical diagnosis (no dementia, possible and probable AD) was based on the following two sets of criteria: (1) the Diagnostic Statistical Manual of Mental Disorders (DSM-IV) plus the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and (2) the National Institute on Aging-Alzheimer's Association (NIA-AA). The Fazekas visual scale was applied when a magnetic resonance imaging scan was available. Results: We included 94 patients, mean age 77.7 years, mean Mini Mental State Examination score 23.9. The concordance (kappa coefficient) between the two sets of clinical criteria was 70%. The mean CSF concentration (pg/ ml) (+/- SD) of biomarkers was as follows: A beta 687 (+/- 318), Tau 492 (+/- 515), and p-Tau 63 (+/- 56). There was a trend for lower A beta and higher Tau levels from the no dementia to the probable AD group. Thepercentage of abnormal liquor according to the local cutoffs was still 15 and 21% in patients without AD based on the DSM-IV plus NINCDS- ADRDA or the NIA-AA criteria, respectively. The exclusion of patient in whom normotensive hydrocephalus was suspected did not change these findings. A total of 80% of patients had the neuroimaging report describing chronic cerebrovascular damage, while the Fazekas scale was positive in 45% of patients overall, in 1/2 of no dementia or possible AD patients, and in about 1/3 of probable AD patients, with no difference across ages. Conclusion: We confirmed the expected discrepancy between different approaches to the diagnosis of AD in a geriatric cohort of patients with cognitive impairment. Further research is needed to understand how to interpret this discrepancy and provide clinicians with practical guidelines.