Trajectories of subjective cognitive decline, and the risk of mild cognitive impairment and dementia

Abstract

Background In cognitively normal individuals, subjective cognitive decline (SCD) has been reported to predict MCI and dementia (MCI/dementia). However, prior studies mostly captured SCD at single time-points without considering the longitudinal course of SCD. This study examined whether the trajectories of SCD provide any added information—beyond one-time assessments of SCD—on the risk of MCI/dementia. Methods This cohort study included 5661 participants from the Alzheimer’s Disease Centers across the USA, who were ≥ 50 years and had normal cognition in the first-four annual visits (year 1 to year 4). The participants were evaluated for SCD in the first-four annual visits (year 1 to year 4), and followed-up almost annually (year 4 up to year 14) for incident MCI/dementia. SCD trajectories (as identified from latent-class-growth-curve-analysis) were included in Cox regression to estimate their risks of MCI/dementia, with analyses further stratified by age (< 75 years versus ≥ 75 years; based on median-split). Results Compared to those without SCD (in the first-four annual visits), Intermittent SCD (i.e., reported in 1–2 of the first-four annual visits) predicted a higher risk (HR 1.4) and Persistent SCD (i.e., reported in 3–4 of the first-four annual visits) predicted the highest risk (HR 2.2), with the results remaining significant even after adjusting for baseline SCD. Age-stratified analysis revealed that the risk associated with Intermittent SCD was only present in older individuals, while risk related to Persistent SCD was consistently present across the younger and older age groups. Age compounded the effects of the trajectories, whereby older individuals with Persistent SCD had > 75% probability of developing MCI/dementia by 10 years, in contrast to < 25% probability by 10 years in younger individuals with No SCD. Conclusions The findings demonstrate the utility of SCD trajectories—especially when used in combination with age strata—in identifying high-risk populations for preventive interventions and trials. They also suggest a potential modification in the current SCD criteria, with the inclusion of “persistent SCD over several years” as a feature of SCD plus.

Circulating Neurofilament Light Predicts Cognitive Decline in Patients With Post-stroke Subjective Cognitive Impairment

“…Furthermore, the linear regression models found that lower TICS-40 scores at baseline and higher serum NfL levels were associated with a worse cognitive performance at endpoint and a larger decrease of TICS-40 scores during follow-up. This study failed to figure out the association of other factors, including age and vascular risk factors such as hypertension or diabetes mellitus, with the longitudinal cognitive decline post-stroke, which is not consistent with previous studies (Jessen et al, 2020;Lee et al, 2020;Liew, 2020). This phenomenon might be attributed to the fact that the subjects in this study had relatively old age and that the follow-up period is not long enough for the observation of the contribution of these factors to cognitive decline.…”

“…Subjective cognitive impairment (SCI) is a common complaint post-acute ischemic stroke (AIS), with a prevalence estimates ranging between 30 and 90% (Van Rijsbergen et al, 2014, 2020Burns et al, 2019). SCI has been reported to be associated with an increased risk of progressing to objective cognitive impairment (OCI), including mild cognitive impairment (MCI) and dementia (Lee et al, 2020;Liew, 2020). Once the patients advanced to OCI stage, the quality of life would be adversely affected.…”

Does “one size fit all” in subjective cognitive decline?

“…Indeed, stratifying SCD individuals by depressive symptoms, Bouldin and colleagues reported that, after adjusting for sociodemographic factors, mental distress was associated with SCD-related unmet needs only among those who had never been diagnosed with depression. This result suggests that the relationship between depression and SCD is more convoluted than might have previously been thought (Liew, 2019). Recently, in a review of magnetic resonance imaging studies, we reported a heterogeneous neurodegenerative profile in SCD, which could depend on subclinical mental distress, such as anxiety and depression (Pini and Wennberg, under review).…”

“…Evaluation of mental distress might be relevant to identify those SCD individuals with unmet needs. However, it is worthwhile to highlight that depression and SCD are two independent constructs that might independently lead to neurodegenerative disorders through different neurobiological pathways (Liew, 2019). Indeed, stratifying SCD individuals by depressive symptoms, Bouldin and colleagues reported that, after adjusting for sociodemographic factors, mental distress was associated with SCD-related unmet needs only among those who had never been diagnosed with depression.…”

MASCoD—Multidimensional Assessment of Subjective Cognitive Decline

“…Over time, the trajectories of SCD can be three: (a) reversible complaint due to other etiologies (e.g., mood disorders, medication side-effects), (b) non-reversible but stable complaint probably due to physiological aging, (c) progressive cognitive decline ( Jessen et al, 2020 ; Liew, 2020b ). Specifically, SCD can be a prodromal symptom of Mild Cognitive Impairment—MCI ( van Harten et al, 2018 ; Boel et al, 2022 ) or dementia ( Liew, 2020a ; Numbers et al, 2021 ; Topiwala et al, 2021 ).…”