Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study

Abstract

Objective Longitudinal studies have shown an increase in cognitive decline many years prior to clinical diagnosis of dementia. We sought to estimate changes, relative to “normal” aging, in the trajectory of a global cognitive function test - the Cognitive Abilities Screening Instrument (CASI). Design A cohort of cognitively intact elderly participants, assessed biennially for dementia for up to 20 years. Setting Community dwelling elderly enrolled in a health maintenance organization. Participants Four thousand three hundred fifteen participants aged 65 and older who had no dementia diagnosis at baseline and had at least 2 visits with valid CASI test score. Measurements Average longitudinal trajectories, including changes in trajectory prior to clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. Results Increased cognitive decline relative to “normal” aging was evident in CASI IRT at least 10 years prior to clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change-point was estimated at an average of 3.1 years (95% confidence interval 3.0, 3.2) prior to clinical diagnosis, after which cognitive decline appeared to accelerate. The change-point did not differ by sex, education level, or APOE ε4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε4 genotype, but not by education. Conclusion Decline in average global cognitive function was evident at least 10 years prior to clinical diagnosis of dementia. The decline accelerated about 3 years prior to clinical diagnosis.

Memory profiles predict dementia over 23–28 years in normal but not successful aging

“…These findings are in line with previous work suggesting that person-specific factors such as genetics and comorbidity may contribute to differences in trajectories prior to death (Wilson et al, 2007;Fabbri et al, 2016;Gerstorf and Ram, 2013). We extend previous studies of competing risks for dementia and death (Li et al, 2017;Prince et al, 2014) by studying two types of dementia disorders, AD and VaD. Although, similar associations were found between the memory groups and AD or VaD risk, the predictors of AD and VaD were different, where female gender and APOE ε4 were risk factors for AD but not for VaD.…”

“…This long preclinical stage provides a critical window for intervention and suggests that thorough neuropsychological assessments are important for early detection. Some studies have observed accelerated decline in multiple cognitive functions in the prodromal phase, starting 3-6 years before clinical symptoms (Albert et al, 2014;Amieva et al, 2004;Cloutier et al, 2015;Li et al, 2017;Wilson et al, 2011). These studies have followed initially cognitively normal individuals longitudinally and examined if an accelerated cognitive rate of change precedes clinical diagnosis.…”

Disease progression modeling of Alzheimer’s disease according to education level

“…Instead, previous modeling studies have reported different disease progression rates depending on disease severity, [12][13][14] the prediction of disease onset time, 15 and the impact of biomarkers on the disease course. 14,[16][17][18] In addition, our model is based on the CDR-SB, which is one of the most widely used dementia staging systems, and represents a validated, well-described, and reliable measure of disease progression. 19,20 The CDR-SB has the advantage of being able to measure changes precisely over time from the preclinical stage to the end state of disease.…”

Greater cognitive decline relative to normal ageing occurs at least 10 years prior to clinical dementia diagnosis

“…Using data from the Adult Changes in Thought (ACT) study, a longitudinal cohort study1 of a US population with ongoing enrolment and biannual visits, Li and colleagues assessed changes in cognitive trajectory and timing of accelerated cognitive decline relative to normal ageing in 4315 people. Item Response Theory (IRT) scores of the Cognitive Abilities Screening Instrument (CASI) were used to estimate cognitive trajectories.…”