Clinical Manifestations

Understanding early signs of cognitive decline in preclinical Alzheimer´s disease may open early intervention to slow down disease progression. We aimed to study the association between Amyloid-β42/40 (Aβ) and cognitive decline, in a population-based cohort of 70-year-olds followed over 5 to 7 years.

The baseline sample (n = 250) was drawn from the 2014 - 2016 assessments conducted within the H70 Gothenburg Birth Cohort Study (n = 1203, response rate=72%), Sweden. At age 70, 322 (26%) individuals consented to lumbar puncture. Participants with dementia (n = 5) or CDR score ≥ 1 (n = 1) were excluded. Participants who underwent cognitive examination at baseline and follow-up (2019 - 2022) were included, resulting in a sample of 250 participants. Cerebrospinal fluid (CSF) levels of Aβ42, Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) were measured. Six cognitive domains (memory, attention, executive function, verbal fluency, visuospatial abilities, and processing speed) were created after z-standardizing raw scores from 11 neuropsychological tests. These were combined into a composite score. Multiple linear regression models were used to evaluate the associations between Aβ42/40 and change in composite score and cognitive domains, adjusting for age, sex, and years of education.

Of the 250 participants, 121 (48.4%) were female and the mean age at follow-up was 76.06 (SD 0.48). At baseline, the prevalence of Aβ pathology (Aβ42/40 ≤0.082) was 25.9%, t-tau (≥350 pg/mL) 29.2%, and p-tau (≥80 pg/mL) 5.6%, as previously published in a partially overlapping subsample (Kern et al., 2018). Lower levels of Aβ42/40 were associated with a steeper decline in processing speed over the follow-up period (β 0.123; 95% CI [0.018 - 1.042]). No significant associations were found between Aβ42/40 and changes in the other five cognitive domains or the composite score. Additionally, women showed a slower decline than men in the composite score (β 0.248; 95% CI [0.081 - 0.302]).

Our results suggest that a decline in cognitive processing speed is associated with lower CSF Aβ42/40 before a decline in other cognitive domains appears. Additionally, our results indicate that females experience a slower rate of cognitive decline than males, between ages 70 and 76, independent of Aβ42/40.