Subjective cognitive decline predicts future dementia risk, study finds

In a recent study published in the journal JAMA Psychiatry, researchers investigated the risk of subjective cognitive decline (SCD) in cognitively normal adults for developing mild cognitive impairment (MCI), Alzheimer’s disease (AD), and all-cause dementia.

Their findings indicate that SCD is significantly associated with an increased risk of future cognitive impairment and dementia, suggesting that SCD may serve as an independent risk factor for these conditions beyond genetic predispositions.

Study: Subjective Cognitive Decline Plus and Longitudinal Assessment and Risk for Cognitive Impairment. Image Credit: Lightspring / Shutterstock

Background

Detecting AD early, before symptoms fully develop, is crucial for effective treatment and prevention. One way to spot early signs is through subjective cognitive decline (SCD), which occurs when people notice their memory or thinking problems even though standard tests show they are normal.

Research has shown that SCD can be an early indicator of future memory problems or AD, but most of this research has been done with people who seek medical help and may have higher risks of developing AD.

Community-based studies, which examine people who do not seek medical help, offer a more accurate picture of how SCD affects the general population. However, these studies often have limitations, such as small sample sizes, only one-time assessments, and less thorough testing.

About the study

To fill gaps in the research, the current study used long-term data from the Framingham Heart Study, which follows a large group of people over time.

Participants aged 60 and older with normal cognition were included and followed from 2005 to 2019. The study assessed SCD through questions about memory concerns at different visits.

Researchers used standard criteria to diagnose MCI, AD, and all-cause dementia. They collected genetic information, including the presence of genes associated with AD risk, from blood samples and calculated a polygenic risk score (PRS) to measure overall genetic risk for AD.

Statistical models compared the risk of developing MCI, AD, and dementia between those with and without SCD after adjusting for factors like age, sex, education, genetic risk, depression, and other health conditions. Additional analyses looked at specific features of SCD (called SCD-plus) to better understand its role in predicting cognitive decline.

By including these genetic factors and specific features of SCD (called SCD-plus), the study aimed to understand the risk of developing serious memory problems in the general population.

Findings

The study included 3,585 individuals with an average age of 68. Approximately 55.1% of the sample were women, and 91.6% were non-Hispanic White individuals. Of the participants, 50.3% were college graduates, and 21.5% carried a gene linked to AD. Participants were followed for approximately 2.1 valid visits each.

During the study period, 6.6% of participants developed MCI, 2.0% developed AD, and 2.5% developed dementia from any cause. On average, SCD appeared 4.4 years before MCI, 6.8 years before AD, and 6.9 years before any dementia. The average age of SCD onset was 69.8 years.

People with SCD during all visits were more likely to be women and reported higher rates of depression. Cognitive impairment rates were higher in this group compared to the no-SCD group: MCI (8.6% vs. 5.8%), AD (3.4% vs. 1.5%), and all-cause dementia (3.9% vs. 2.0%).

Survival analysis showed that SCD was significantly associated with the time to develop MCI, AD, and all-cause dementia. Adjusted for age, sex, and education, the hazard ratios (HR) for SCD were 1.60 for MCI, 4.33 for AD, and 2.17 for all-cause dementia.

After accounting for genetic predisposition to dementia, the HRs remained significant: 1.57 for MCI, 2.98 for AD, and 2.14 for all-cause dementia. Depression and other cardiovascular factors slightly reduced the HRs, but SCD remained a significant predictor.

The results indicated a strong and consistent link between SCD and the risk of future cognitive impairment, emphasizing the importance of monitoring SCD in older adults.

Conclusions

This large longitudinal study found that SCD is a significant predictor of MCI, AD, and all-cause dementia, aligning with previous research. SCD typically preceded MCI by 4.4 years, AD by 6.8 years, and all-cause dementia by 6.9 years.

The study’s strengths include its large, community-based sample and longitudinal design, enhancing the reliability of the findings. However, limitations include low rates of cognitive impairment, potential underestimation of SCD cases due to infrequent assessment, and lack of AD biomarkers.

Future research should address these limitations and explore SCD’s predictive utility in more diverse populations to improve early screening and intervention strategies.