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Introduction: Late-life depression frequently coexists with cognitive impairment, and hypovitaminosis D has been implicated in both conditions. We examined the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and cognition among older adults with major depressive disorder (MDD). Materials and Methods: Cross-sectional study at a tertiary-care geriatric psychiatry clinic. Consecutive patients aged ≥60 years with DSM-5 MDD were enrolled. Exclusions: dementia diagnosis, delirium, severe neurological disease, current high-dose vitamin D, or malabsorption. Depression severity was measured by GDS-15; cognition by MoCA-Basic; disability by WHODAS-12. Fasting 25(OH)D was quantified (LC–MS/MS). Vitamin D status: deficient <20 ng/mL, insufficient 20–29 ng/mL, sufficient ≥30 ng/mL. Multivariable linear and logistic regressions assessed associations between 25(OH)D and cognitive outcomes adjusting for age, sex, education, BMI, comorbidity, antidepressant use, physical activity, and season. Results: N=220 (mean age 68.8±6.3 y; 58% women). Vitamin D deficiency was present in 41.8%, insufficiency in 33.2%. Mean MoCA-B score was 22.1±3.9; mild cognitive impairment (MCI) threshold (<25) was met by 62.3%. Each 10 ng/mL higher 25(OH)D associated with +1.1 MoCA-B points (β=0.11 per ng/mL; p<0.001) and lower odds of MCI (aOR 0.68, 95% CI 0.52–0.88). Compared with sufficiency, deficiency had lower MoCA-B (−2.3 points, p<0.001) and higher odds of executive dysfunction (Trails-B time ≥1.5 SD; aOR 1.94, 95% CI 1.10–3.45) Conclusion: In geriatric depression, lower 25(OH)D correlates with worse global cognition and executive function independent of confounders. Given mixed trial data, screening and correction of deficiency may be reasonable as part of comprehensive care while prioritizing evidence-based depression and cognitive interventions.
Depression in older adults is common and clinically consequential, frequently accompanied by deficits in memory, attention, and executive function that worsen disability and increase dementia risk.¹ Elevated rates of hypovitaminosis D in aging populations have prompted interest in its role in mood and cognition via neurotrophic, anti-inflammatory, and vasculoprotective pathways.² Vitamin D receptors and 1α-hydroxylase are expressed in hippocampus and cortex, supporting plausibility for cognitive effects through modulation of neurotrophins (e.g., BDNF), neurotransmission, and microglial activation.³
Observational studies generally associate lower serum 25-hydroxyvitamin D [25(OH)D] with higher odds of late-life depression and cognitive decline, though heterogeneity in assays, thresholds, and confounding complicates inference.⁴ Randomized evidence for vitamin D supplementation improving mood is mixed: a large, long-term RCT in community-dwelling older adults (VITAL-DEP) found no preventive effect on depression incidence,⁵ while some meta-analyses suggest symptomatic benefits in specific subgroups (baseline insufficiency, higher doses, or primary depression).⁶ For cognition, trials show inconsistent effects, with several reporting null changes on global tests despite biological plausibility.⁷ Nevertheless, in clinical practice, deficiency remains common, and updated endocrine guidance supports empiric supplementation in adults ≥75 years or other high-risk groups while not recommending routine population testing.⁸
Late-life depression (LLD) presents unique pathophysiology characterized by cerebrovascular burden, inflammation, and HPA-axis dysregulation—all processes potentially influenced by vitamin D.⁹ Given high comorbidity among low vitamin D, depressive symptoms, and cognitive impairment, it is clinically useful to clarify whether lower 25(OH)D correlates with cognition within a geriatric depression cohort rather than general older populations. We therefore evaluated: (i) the cross-sectional association between 25(OH)D and global cognition; (ii) domain-specific effects (executive function, attention); and (iii) whether vitamin D deficiency independently associates with MCI in patients with major depressive disorder after accounting for confounders.
This is an Analytical cross-sectional study conducted from January–September 2025 at the Geriatric Psychiatry outpatient services of a tertiary-care center.
Inclusion: (1) Age ≥60 years; (2) DSM-5 major depressive disorder (current episode or within 6 months) diagnosed by psychiatrist; (3) Able to provide consent (or with surrogate consent).
Exclusion: (1) Major neurocognitive disorder/dementia (DSM-5) or MoCA-B <15; (2) Delirium; (3) History of stroke within 6 months, Parkinson’s disease, multiple sclerosis, epilepsy with recent seizures, or severe traumatic brain injury; (4) Current high-dose vitamin D (>2000 IU/day in last 3 monts) or intramuscular depot in 6 months; (5) Malabsorption, chronic liver failure, stage 5 CKD; (6) Antipsychotic initiation in past 4 weeks; (7) Uncorrected visual/hearing impairment precluding testing.
Assessments:
Statistical analysis: Descriptive statistics for groups by vitamin D status. Between-group comparisons by t-test/ANOVA or χ². Pearson correlations for continuous 25(OH)D with MoCA-B and TMT-B. Primary models: (a) multivariable linear regression (MoCA-B as continuous outcome) and (b) logistic regression (MCI yes/no). Covariates chosen a priori: age, sex, education, BMI, Charlson index, antidepressant use (SSRI/SNRI/other), physical activity, and season. Secondary models examined executive dysfunction (TMT-B ≥1.5 SD above age-education norms). Two-sided p<0.05 considered significant. Analyses in R 4.3.1.
Ethics: Institutional Ethics Committee approved the protocol; all participants provided written informed consent consistent with the Declaration of Helsinki.
Table 1. Baseline characteristics by vitamin D status (N=220)
|
Characteristic |
Deficient <20 (n=92) |
Insufficient 20–29 (n=73) |
Sufficient ≥30 (n=55) |
p-value |
|
Age, years (mean±SD) |
69.4±6.6 |
68.6±6.1 |
68.0±5.7 |
0.42 |
|
Women, n (%) |
60 (65.2) |
39 (53.4) |
29 (52.7) |
0.18 |
|
Education, years |
9.1±4.2 |
10.3±4.5 |
11.2±4.7 |
0.03 |
|
BMI, kg/m² |
25.9±3.8 |
25.6±3.6 |
24.9±3.5 |
0.24 |
|
Charlson index |
2.0±1.1 |
1.9±1.0 |
1.7±0.9 |
0.21 |
|
Antidepressant (SSRI), % |
58.7 |
56.2 |
49.1 |
0.43 |
|
Physical activity (≥150 min/wk), % |
21.7 |
28.8 |
36.4 |
0.07 |
Groups were broadly comparable; the sufficient group had slightly higher education and activity.
Table 2. Vitamin D distribution and symptom burden
|
Variable |
Overall |
|
25(OH)D, ng/mL (mean±SD) |
23.9±9.8 |
|
Deficiency, n (%) |
92 (41.8) |
|
Insufficiency, n (%) |
73 (33.2) |
|
Sufficiency, n (%) |
55 (25.0) |
|
GDS-15 score (mean±SD) |
8.1±3.2 |
|
WHODAS-12 (mean±SD) |
16.7±7.3 |
Hypovitaminosis D (deficient/insufficient) was prevalent (75%).
Table 3. Cognitive outcomes by vitamin D category
|
Outcome |
Deficient |
Insufficient |
Sufficient |
p-trend |
|
MoCA-B (0–30) |
20.9±3.7 |
22.4±3.6 |
23.2±3.8 |
<0.001 |
|
MCI (MoCA-B <25), % |
74.0 |
63.0 |
38.2 |
<0.001 |
|
TMT-B time, sec |
185±64 |
169±58 |
152±55 |
0.002 |
|
Executive dysfunction* (%) |
44.6 |
31.5 |
20.0 |
0.001 |
*Executive dysfunction defined as TMT-B ≥1.5 SD above age-education norms.
Interpretation: Lower vitamin D associated with worse global and executive performance.
Table 4. Correlation of continuous 25(OH)D with cognition
|
Correlate |
r |
p-value |
|
25(OH)D vs MoCA-B |
+0.34 |
<0.001 |
|
25(OH)D vs TMT-B time |
−0.27 |
<0.001 |
|
25(OH)D vs Digit Span total |
+0.19 |
0.006 |
Higher 25(OH)D correlated with better global, executive, and attention performance.
Table 5. Multivariable models (adjusted associations)
|
Outcome & Model |
Key exposure |
Effect (95% CI) |
p |
|
Linear: MoCA-B (per 1 ng/mL ↑ 25(OH)D) |
Continuous 25(OH)D |
β=+0.11 (0.06, 0.16) |
<0.001 |
|
Logistic: MCI (yes/no) |
Per 10 ng/mL ↑ 25(OH)D |
aOR 0.68 (0.52, 0.88) |
0.003 |
|
Logistic: Executive dysfunction |
Deficiency vs sufficiency |
aOR 1.94 (1.10, 3.45) |
0.021 |
|
Linear: MoCA-B |
Deficiency vs sufficiency |
β=−2.3 (−3.3, −1.3) |
<0.001 |
Adjusted for age, sex, education, BMI, Charlson, antidepressant class, physical activity, season.
Interpretation: Associations persisted after rigorous adjustment.
Table 6. Subgroup analyses (primary outcome: MoCA-B)
|
Subgroup |
β per 10 ng/mL ↑ 25(OH)D (MoCA-B points) |
Interaction p |
|
Age 60–69 (n=124) |
+1.0 (0.4, 1.6) |
— |
|
Age ≥70 (n=96) |
+1.2 (0.6, 1.9) |
0.58 |
|
Education ≤8 y |
+1.3 (0.6, 2.0) |
— |
|
Education >8 y |
+0.9 (0.4, 1.5) |
0.41 |
|
Women |
+1.1 (0.5, 1.8) |
— |
|
Men |
+1.0 (0.3, 1.7) |
0.89 |
Benefits of higher vitamin D were consistent across key subgroups.
In this geriatric depression cohort, lower serum 25(OH)D concentrations were independently associated with poorer global cognition and greater executive dysfunction. Each 10 ng/mL increment in 25(OH)D corresponded to ~1 MoCA-B point higher and ~32% lower odds of MCI after adjustment. These findings align with population studies linking hypovitaminosis D to cognitive decline and dementia risk in older adults,⁴,¹⁵ and with observational work connecting lower vitamin D to depressive symptom burden in aging cohorts.¹,²¹
Mechanistically, vitamin D may support cognition via modulation of neurotrophins (e.g., increased hippocampal BDNF), neuroinflammation, calcium homeostasis, and cerebrovascular integrity.³,¹⁷,²⁰ Narrative and structured reviews increasingly implicate BDNF-related pathways, with some reports of improved mood scores and modest BDNF increases following supplementation when baseline levels are low.¹⁷,²４ Still, causality remains uncertain.
Our results complement trial evidence while highlighting a key distinction: most large RCTs in nondepressed or mixed older adults—often with near-sufficient baseline 25(OH)D—show null effects on incident depression or global cognition.⁵,²³,⁸,¹¹ Meta-analyses, however, suggest potential antidepressant effects in adults with primary depression at higher doses or with insufficiency,⁶,¹４ and small trials indicate domain-specific cognitive signals in selected subgroups.⁸ The heterogeneity underscores that, although low vitamin D correlates with worse cognition in LLD (as here), supplementation may not uniformly reverse deficits, particularly if deficiency is not present or if vascular/inflammatory drivers dominate.
Clinical implications are pragmatic: prevalence of hypovitaminosis D in older adults with depression is high in our sample and others,¹,²¹ and current endocrine guidance supports empiric supplementation for adults ≥75 years or other risk groups while discouraging routine population testing.⁸,¹⁹ Correcting deficiency is safe, inexpensive, and may contribute to multidomain care alongside evidence-based depression treatments, cognitive training, exercise, vascular risk control, and sleep optimization.²²
Strengths include focused enrollment of geriatric MDD patients, standardized LC–MS/MS vitamin D assay, and control for multiple confounders. Limitations include cross-sectional design (precluding causality), single-center sampling, and residual confounding (e.g., sun exposure, diet). Cognitive assessment relied on MoCA-Basic and select executive/attention tests; comprehensive neuropsychological batteries and longitudinal follow-up would refine domain-specific trajectories. Interventional studies that target deficient LLD patients, stratify by baseline 25(OH)D, and assess BDNF/inflammatory biomarkers may clarify who benefits cognitively.
In summary, within geriatric depression, lower 25(OH)D is robustly associated with worse cognition. Pending definitive trials in this high-risk phenotype, it is reasonable to screen for and correct deficiency as part of comprehensive LLD care while setting expectations that supplementation complements—but does not replace—standard depression and cognitive interventions.⁵,⁸
Among older adults with major depression, vitamin D deficiency and insufficiency are common and correlate with worse global and executive cognitive performance independent of age, education, comorbidity, and treatment. While trials in unselected elders often show null effects of supplementation on mood or cognition, targeted correction of deficiency within geriatric depression may be a rational adjunct to multimodal care. Longitudinal and interventional studies in vitamin D–deficient LLD cohorts are warranted.
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