OBJECTIVES: Many patients with Alzheimer’s disease (AD) have comorbidities such as cardiovascular disease (CVD). AD symptoms such as neuropsychiatric symptoms (NPS) and urinary incontinence (UI) may also be considered as comorbidities. However, data synthesis is required on the progression of comorbidities with increasing AD severity, and the role of comorbidities in AD progression. We designed a systematic literature review to identify studies that assessed associations between comorbidities in AD and Clinical Dementia Rating (CDR) scale Global or Sum of Boxes (CDR-SB) scores, two widely used AD staging measures.

METHODS: Embase, MEDLINE and the Cochrane Library were searched on 26 November 2021 using terms for AD, CDR/CDR-SB, and comorbidities, without date restriction. All AD stages (mild cognitive impairment and mild, moderate and severe dementia) and study designs were considered relevant.

RESULTS: Overall, 30 studies met the inclusion criteria, of which 14 were full publications that reported detailed data on the association between CDR/CDR-SB scores and comorbidities. Together, these included nearly 7000 patients. Six studies reported data on NPS, most of which indicated that NPS become more frequent with increasing AD severity (higher CDR/CDR-SB scores). In one study, the presence of NPS at baseline predicted AD progression, and AD severity at baseline was linked to subsequent NPS progression. Another study found that increasing CDR scores over time are linked to the progression of depressive symptoms. Five studies reported data on CVD or cardiovascular risk factors; however, no clear association between CVD and AD severity or progression was identified. Two studies found that urge UI is associated with AD severity.

CONCLUSIONS: The link between comorbidities and AD severity measured using the CDR or CDR-SB has not been extensively studied. Although a link between NPS and AD is well established, the interrelationship between AD progression and other conditions remains unknown and requires further investigation.