Clinical Manifestations.

Area of Science:

• Neurology
• Gerontology
• Biochemistry

Background:

• Early detection of cognitive decline in preclinical Alzheimer's disease is crucial for intervention.
• The ratio of Amyloid-β42/40 (Aβ) in cerebrospinal fluid (CSF) is a potential biomarker.
• Longitudinal studies in population-based cohorts are needed to understand Aβ's role in cognitive aging.

Purpose of the Study:

• To investigate the association between CSF Aβ42/40 levels and cognitive decline over 5-7 years in 70-year-olds.
• To examine changes in specific cognitive domains and a composite cognitive score.
• To explore potential sex differences in cognitive decline rates.

Main Methods:

• Analysis of CSF Aβ42, Aβ40, t-tau, and p-tau from 250 participants (aged 70 at baseline) in the H70 Gothenburg Birth Cohort Study.
• Cognitive function assessed using 11 neuropsychological tests across six domains, combined into a composite score.
• Multiple linear regression models adjusted for age, sex, and education to assess Aβ42/40 associations with cognitive change.

Main Results:

• Lower CSF Aβ42/40 levels correlated with a steeper decline in processing speed (β=0.123).
• No significant associations were found between Aβ42/40 and changes in other cognitive domains or the composite score.
• Women exhibited a slower decline in the composite cognitive score compared to men (β=0.248), independent of Aβ42/40.

Conclusions:

• Reduced CSF Aβ42/40 may precede broader cognitive decline, specifically impacting processing speed.
• Cognitive decline progresses slower in women than men between ages 70 and 76.
• CSF Aβ42/40 ratio is a relevant biomarker for early cognitive changes, particularly processing speed decline.