Late-Onset Depression Linked to Increased Dementia Risk, With Lingfeng Xue, PhD

Late-onset depression was associated with poorer performance in fluid intelligence and visuospatial memory, as well as a greater risk of incident dementia, in older adults with major depressive disorder (MDD). In an interview with HCPLive, Lingfeng Xue, PhD, an old age psychiatry and clinical research assistant at King’s College London, discussed the implications of these findings.

“The relationship between late-onset depression and…dementia can be complicated,” Xue said. “The depressive symptoms [can represent a] prodrome of dementia or independently as a risk factor of dementia. These are 2 valid theories, and they both have evidence…there's no exclusive or established theory for 1 against another.”

The analysis evaluated 75,064 adults aged ≥ 60 years from the UK Biobank with linked primary care data, comparing cognitive outcomes and dementia incidence across depression subtypes defined by age at onset.1 Participants with late-life depression with late onset (LLD-LO), defined as the first depressive episode after age 50 years, demonstrated significantly worse performance in fluid intelligence and visuospatial memory compared with both depression-free controls and those with earlier-onset depression. Over a median follow-up of 13.69 years, LLD-LO was associated with an increased risk of incident dementia, with hazard ratios ranging from 1.42 to 1.52 across adjusted models.1

Impairments in fluid intelligence and visuospatial memory partially mediated dementia risk, accounting for 3.1% (95% CI, 1.2% to 5.0%) and 1.4% (95% CI, 0.4% to 2.5%) of the association, respectively.1 Xue noted that such deficits may be detectable in midlife and should prompt further evaluation.

“Any mid-age cognitive loss warrants attention in… real-world practice,” he said, referencing commonly used tools such as the Wechsler Adult Intelligence Scale for reasoning and computerized tasks for visuospatial assessment.

The reported hazard ratio of approximately 1.4 to 1.5 indicates a 40–50% relative increase in dementia risk among individuals with late-onset depression. Xue said this aligns with prior evidence identifying depression as a modifiable risk factor for dementia. He added that first-onset depression after 50 years old should prompt clinicians to consider additional cognitive assessment and longitudinal monitoring.

The study’s use of age 50 years as a cutoff for late-onset depression was intended to increase sensitivity for detecting early cognitive changes. Sensitivity analyses suggested this threshold captured associations with impairment more effectively than higher cutoffs.

Xue cautioned against rigid clinical interpretation of this boundary. Rather, the findings serve more as a reminder that mid-to late-life depression onset is associated with later cognitive decline.

The findings support integrating cognitive screening into the evaluation of patients presenting with first-onset depression in mid- to late life. Xue highlighted the importance of considering both psychiatric and neurological pathways when assessing these patients, particularly given the potential for early cognitive changes to precede clinically recognized dementia.

“The onset of depression after 50 is multi-driven, so the clinician should consider various factors from multiple dimensions into consideration,” Xue said.

References

Xue L, Bocharova M, Young AH, Aarsland D. Late-onset depression predicts cognitive impairment and subsequent dementia among older adults with major depressive disorder: findings from UK Biobank and primary care linked data. BJPsych Open. 2026;12(2):e88. Published 2026 Mar 10. doi:10.1192/bjo.2026.10995