Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults

Neuromolecular Med. 2024 Nov 1;26(1):43. doi: 10.1007/s12017-024-08810-4.

Abstract

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ42,Aβ40,Aβ38), tau, and phospho-tau Thr181. Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ42/Aβ38 could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr181/Aβ42. These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD.

Keywords: Alzheimer disease; ApoE; Biomarkers; Cerebrospinal fluid; Lewy body dementia; Sex.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / cerebrospinal fluid
  • Alzheimer Disease* / genetics
  • Amyloid beta-Peptides* / cerebrospinal fluid
  • Anthropometry
  • Apolipoprotein E4 / genetics
  • Biomarkers* / cerebrospinal fluid
  • Body Mass Index
  • Diagnosis, Differential
  • Female
  • Humans
  • Lewy Body Disease* / cerebrospinal fluid
  • Lewy Body Disease* / genetics
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Sex Factors
  • alpha-Synuclein / cerebrospinal fluid
  • alpha-Synuclein / genetics
  • tau Proteins* / cerebrospinal fluid

Substances

  • Biomarkers
  • tau Proteins
  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Peptide Fragments
  • alpha-Synuclein
  • MAPT protein, human
  • amyloid beta-protein (1-42)
  • SNCA protein, human
  • amyloid beta-protein (1-40)