Developing Topics

Alzheimers Dement. 2024 Dec;20 Suppl 8:e095618. doi: 10.1002/alz.095618.

ABSTRACT

BACKGROUND: Late-life depression (LLD) is a risk factor for cognitive impairment. Some studies have shown an association between higher amyloid-beta (Aβ) burden, a known marker of Alzheimer's Disease (AD), and LLD, but research findings are mixed. We performed a systematic review and meta-analysis to compare the Aβ burden between cognitively unimpaired subjects with and without LLD.

METHOD: We searched MEDLINE, Embase, and ScienceDirect for studies comparing Aβ burden between LLD patients and controls (molecular imaging and/or fluid-biomarker confirmation) and included subjects aged ≥60 years with LLD, and absence of cognitive impairment (MMSE ≥24 and/or description of normal cognition). The review process was performed by 2 independent reviewers (Covidence-software). A random effects meta-analysis was executed to evaluate the pooled difference of Aβ burden between LLD and control groups (JASP-software).

RESULT: 372 studies were identified and eight met the inclusion-exclusion criteria (combined sample: 725 LLD subjects and 885 controls). The weighted-mean age was 69.3 and 68.9 years for subjects and controls. Six studies evaluated Aβ in blood (4 on serum and 2 on plasma, one of them also evaluated PET-Aβ), and two evaluated cerebrospinal fluid (CSF) (table 1). One of the serum studies (Namekawa) included two subgroups, one with subjects that besides depression after 60 years old also had a history of depression before age 60, and one with participants with a first episode of major depressive disorder after 60 years old. Both subgroups were analyzed separately in the meta-analysis. The meta-analysis of plasma and serum studies showed that individuals with LLD had lower levels of Aβ42 (estimate -0.344, p<0.001) (Fig. 1) and higher levels of Aβ40/42 ratio (estimate 0.428, p<0.001) compared to controls (Fig. 2). The results remained significant when plasma and serum were analyzed independently.

CONCLUSION: In this systematic review and meta-analysis, we found significantly lower levels of Aβ42 and higher levels of Aβ40/42 ratio in cognitively unimpaired older adults with LLD compared to controls. These findings support the idea that LLD is associated with AD pathology. This is a relevant area of research for increasing the understanding of AD's clinical presentation that could potentially impact access to early diagnosis and treatment.

PMID:39783357 | DOI:10.1002/alz.095618