Abstract

Background: Despite having the same histopathological characteristics, early-onset and late-onset Alzheimer’s disease (AD) patients show some distinct clinical and neuropsychological profiles. Early Onset Mild Cognitive Impairment (EOMCI) is a less characterized group. The aim of this study is to characterize MCI probably due to AD in terms of the clinical, genetic, Cerebrospinal fluid (CSF) biomarkers profile and conversion rate of EOMCI, compared to the late-onset form (LOMCI). Methods: 159 MCI patients were divided in two groups: 52 EOMCI (onset < 65 years) and 107 LOMCI (onset ≥ 65 years). We investigated differences in neuropsychological scores, clinical variables, ApoE genotype, CSF biomarkers (Aβ42, t-Tau and p-Tau) in both groups. Conversion was ascertained during follow-up. Results: EOMCI showed a longer duration of symptoms prior to the first evaluation (EOMCI = 4.57 vs. LOMCI = 3.31, p = 0.008) and scored higher on the subjective memory complaints scale (9.91 vs. 7.85, p = 0.008), but performed better in brief cognitive tests (27.81 vs. 26.51, p < 0.001 in Mini-Mental State Examination; 19.84 vs. 18.67, p = 0.005 in Montreal Cognitive Assessment) than LOMCI. ApoE genotype distribution and CSF biomarker profile were similar in both groups, as was the conversion risk. Lower Aβ42 (Hazard ratio (HR): 0.998, 95% Confidence Interval (CI) = [0.996–1.000], p = 0.042), higher t-Tau levels (HR: 1.003, 95%CI = [1.000–1.005], p = 0.039) and higher scores in the Alzheimer Disease Assessment Scale-Cognitive (HR: 1.186, 95%CI = [1.083–1.299], p = 0.002) increased the risk of conversion. Discussion: Despite differences in memory performance and memory complaints, EOMCI and LOMCI seem to represent indistinct biological groups that do not have a higher risk of conversion to AD or differ in risk factors for conversion.

Highlights

  • Alzheimer’s disease (AD) is the most common cause of neurodegenerative dementia [1]

  • We aimed to study Mild Cognitive Impairment (MCI) probably due to AD and to better characterize the clinical, genetic, and Cerebrospinal fluid (CSF) biomarkers profiles and conversion rates of Early Onset Mild Cognitive Impairment (EOMCI), compared to the most frequent late-onset form (LOMCI)

  • The study sample consisted of 159 patients: 52 with EOMCI and 107 with LOMCI

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Summary

Introduction

“65 years old” is an arbitrary cut-off, with no true biological meaning [1,2,3], but it is still fully considered in the most recent diagnostic criteria for AD and in selection for clinical trials According to this conventional limit, 1%–6% of all AD patients have an early-onset disease [4]. Despite having the same histopathological characteristics, early-onset AD and late-onset AD seem to show some distinct clinical and neuropsychological profiles [5]. Despite having the same histopathological characteristics, early-onset and late-onset Alzheimer’s disease (AD) patients show some distinct clinical and neuropsychological profiles. The aim of this study is to characterize MCI probably due to AD in terms of the clinical, genetic, Cerebrospinal fluid (CSF) biomarkers profile and conversion rate of EOMCI, compared to the late-onset form (LOMCI).

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