Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure.

Cross-sectional study

Academic Health Center

Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust)

LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0–5), classifying subjects as robust (0), prefrail (1–2), and frail (3–5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM).

We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = −26,−11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large.

We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression–frailty phenotype in older adults.

Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia.

To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies.

A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression.

Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P< 0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P=0.03).

Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.

Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of lithium in Alzheimer's disease, although no benefits were obtained from short-term treatment.

To evaluate the effect of long-term lithium treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI).

Forty-five participants with aMCI were randomised to receive lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: NCT01055392.

Lithium treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer's Disease Assessment Scale and in attention tasks. Overall tolerability of lithium was good and the adherence rate was 91%.

The present data support the notion that lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer's disease.