Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce.

This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms.

VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume).

Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Vascular risk factors including hypertension, diabetes and dyslipidaemia promote diverse pathological mechanisms in the brain leading to cerebral hypoperfusion and ultimately cognitive decline in people. Medial temporal, medial frontal and anterior cingulate atrophy has been closely associated with diabetes and medial temporal lobe atrophy is associated with hypertension in people with Alzheimer’s disease (AD).

To assess if hypertension, diabetes and dyslipidaemia have differential effects on different brain locations using brain imaging in people with AD.

The current study is based on [18F] fluorodeoxyglucose- positron emission tomography (FDG-PET) data of 970 participants from two large Phase III multi-centre clinical trials of a novel tau aggregation inhibitor drug Leuco-Methylthioninium (LMTX)meeting research criteria for mild to moderate AD. Vascular risk factor data including hypertension, diabetes and dyslipidaemia were collected and quantification of FDG PET hypo-metabolism was done by calculating Standardized Uptake Value Ratio(SUVR).

Hypertension, diabetes and dyslipidaemia were found to have differential effects on brain locations in people with AD. When people with hypertension, diabetes and dyslipidaemia were compared to those without, mean SUVR was increased significantly in both left and right parietal and occipital lobes and decreased in left and right anterior cingulate gyri in hypertensives. SUVR was significantly higher in both left and right temporal lobes in diabetics andlower in both left and right anterior cingulate gyri in people with dyslipidaemia.

Vascular risk factors including hypertension, diabetes and dyslipidaemia have differential effects on different brain regions, measured using SUVR analysis of FDG-PET.

The FDG-PET data was taken from participants of two large phase III clinical trials sponsored by TauRx Therapeutics (Singapore). TauRx Therapeutics has contributed towards my studentship during my PhD but the data related to drug used in the clinical tria

To compare the prevalence of select cardiovascular risk factors (CVRFs) in patients with mild cognitive impairment (MCI) versus lifetime history of major depression disorder (MDD) and a normal comparison group using baseline data from the Prevention of Alzheimer’s Dementia with Cognitive Remediation plus Transcranial Direct Current Stimulation (PACt-MD) study.

Baseline data from a multi-centered intervention study of older adults with MCI, history of MDD, or combined MCI and history of MDD (PACt-MD) were analyzed.

Community-based multi-centered study based in Toronto across 5 academic sites.

Older adults with MCI, history of MDD, or combined MCI and history of MDD and healthy controls.

We examined the baseline distribution of smoking, hypertension and diabetes in three groups of participants aged 60+ years in the PACt-MD cohort study: MCI (n = 278), MDD (n = 95), and healthy older controls (n = 81). Generalized linear models were fitted to study the effect of CVRFs on MCI and MDD as well as neuropsychological composite scores.

A higher odds of hypertension among the MCI cohort compared to healthy controls (p < .05) was noted in unadjusted analysis. Statistical significance level was lost on adjusting for age, sex and education (p > .05). A history of hypertension was associated with lower performance in composite executive function (p < .05) and overall composite neuropsychological test score (p < .05) among a pooled cohort with MCI or MDD.

This study reinforces the importance of treating modifiable CVRFs, specifically hypertension, as a means of mitigating cognitive decline in patients with at-risk cognitive conditions.

In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients.

The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification.

Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510–24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000).

AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.

Several studies suggest that patients with late-onset major depression (MD) have an increased load of cerebral white-matter lesions (WMLs) compared with age-matched controls. Vascular risk factors such as hypertension and smoking may confound such findings. Our aim was to investigate the association between the localization and load of WMLs in late-onset MD with respect to vascular risk factors.

We examined 22 consecutive patients with late-onset first-episode MD and 22 age- and gender-matched controls using whole-brain magnetic resonance imaging (MRI). The localization, number and volume of WMLs were compared between patients and controls, while testing the effect of vascular risk factors.

Among subjects with one or more WMLs, patients displayed a significantly higher WML density in two white-matter tracts: the left superior longitudinal fasciculus and the right frontal projections of the corpus callosum. These tracts are part of circuitries essential for cognitive and emotional functions. Analyses revealed no significant difference in the total number and volume of WMLs between groups. Patients and controls showed no difference in vascular risk factors, except for smoking. Lesion load was highly correlated with smoking.

Our results indicate that lesion localization rather than lesion load differs between patients with late-onset MD and controls. Increased lesion density in regions associated with cognitive and emotional functions may be crucial in late-onset MD, and vascular risk factors such as smoking may play an important role in the pathophysiology of late-onset MD, consistent with the vascular depression hypothesis.