Trajectories of dementia-related cognitive decline in a large mental health records derived patient cohort

Abstract

Background: Modeling trajectories of decline can help describe the variability in progression of cognitive impairment in dementia. Better characterisation of these trajectories has significant implications for understanding disease progression, trial design and care planning.

Methods: Patients with at least three Mini-mental State Examination (MMSE) scores recorded in the South London and Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories of cognitive decline were identified through latent class growth analysis of longitudinal MMSE scores. Demographics, Health of Nation Outcome Scales and medications were compared across trajectories identified.

Results: Four of the six trajectories showed increased rate of decline with lower baseline MMSE. Two trajectories had similar initial MMSE scores but different rates of decline. In the faster declining trajectory of the two, a higher incidence of both behavioral problems and sertraline prescription were present.

Conclusions: We find suggestive evidence for association of behavioral problems and sertraline prescription with rate of decline. Further work is needed to determine whether trajectories replicate in other datasets.

Fig 1. Six trajectories optimally explain the heterogeneity in cognitive decline in this SLaM NHS Trust patient sample with at least three MMSE scores.

The trajectories show trend of lower initial baseline MMSE score and faster rate of decline. Trajectory 4 is distinct in that is has a similar baseline MMSE score to trajectory 3 but a similar rate to that of trajectory 6.

Fig 2. Six trajectories identified in the latent class growth analysis with estimated profile and individual level MMSE profiles.

Trajectory 1 (A) to Trajectory 6 (F).

Fig 3. Forest plot of relative risk ratios (RRR) and confidence intervals for baseline characteristics of trajectory 3 compared to trajectory 4 from multinomial regression.

Trajectory 3 is at lower risk of moderate or severe behavioral disturbances and Sertraline prescription (RRR <1), is older and at higher risk of mild cognitive problems and moderate or severe other mental health and behavioral difficulties (RRR > 1) than trajectory 4. RRR of 1 indicate no difference between trajectories. Confidence intervals including 1 are non-significant.

Fig 4. Proportions of diagnoses in the patient sample from SLaM CRIS.

(A) Diagnosis types of the total sample; 78% of subjects have at least one diagnosis of dementia, 33% of subjects have at least one other mental health diagnosis, 18% have at least one of both dementia and other mental health diagnoses, (B) diagnosis types in each trajectory; Trajectory 1 has the highest proportion with other mental health diagnosis and lowest with dementia. Conversely, trajectories 5 and 6 have the highest proportion with dementia diagnoses and lowest with other mental health diagnoses. Trajectory 4 has the highest proportion of subjects with both dementia and other Mental Health diagnoses. (C) Dementia diagnoses in each trajectory; each dementia diagnosis differs significantly in proportion across trajectory classes, with the exception of FTD and Parkinson's (p < 0.05) (D) Other mental health diagnoses in each trajectory; all diagnoses differ significantly across trajectory classes with the exception of bipolar and behavioral diagnoses. (E) Comparison of dementia diagnosis in trajectories 3 and 4; significantly lower proportion of subjects with Alzheimer's diagnosis, but higher proportion of VD, MCI and LBD diagnoses in trajectory 4. (F) Comparison of other mental health diagnoses in trajectories 3 and 4; significantly higher proportion of subjects with depression, anxiety, psychosis and schizophrenia in trajectory 4.