scholarly journals Pathomechanisms of Vascular Depression in Older Adults

2021 ◽  
Vol 23 (1) ◽  
pp. 308
Author(s):  
Kurt A. Jellinger
Keyword(s):  
Risk Factors ◽  
Depressive Disorder ◽  
Functional Disability ◽  
Small Vessel Disease ◽  
Executive Dysfunction ◽  
Vascular Risk Factors ◽  
Reciprocal Relationship ◽  
Vascular Risk ◽  
Cerebrovascular Lesions ◽  
Vascular Depression

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated with high disability, cognitive decline, and increased mortality The factors predicting the risk of late-life depression (LLD) are incompletely understood. The reciprocal relationship of depressive disorder and age- and disease-related processes has generated pathogenic hypotheses and provided various treatment options. The heterogeneity of depression complicates research into the underlying pathogenic cascade, and factors involved in LLD considerably differ from those involved in early life depression. Evidence suggests that a variety of vascular mechanisms, in particular cerebral small vessel disease, generalized microvascular, and endothelial dysfunction, as well as metabolic risk factors, including diabetes, and inflammation that may induce subcortical white and gray matter lesions by compromising fronto–limbic and other important neuronal networks, may contribute to the development of LLD. The “vascular depression” hypothesis postulates that cerebrovascular disease or vascular risk factors can predispose, precipitate, and perpetuate geriatric depression syndromes, based on their comorbidity with cerebrovascular lesions and the frequent development of depression after stroke. Vascular burden is associated with cognitive deficits and a specific form of LLD, vascular depression, which is marked by decreased white matter integrity, executive dysfunction, functional disability, and poorer response to antidepressive therapy than major depressive disorder without vascular risk factors. Other pathogenic factors of LLD, such as neurodegeneration or neuroimmune regulatory dysmechanisms, are briefly discussed. Treatment planning should consider a modest response of LLD to antidepressants, while vascular and metabolic factors may provide promising targets for its successful prevention and treatment. However, their effectiveness needs further investigation, and intervention studies are needed to assess which interventions are appropriate and effective in clinical practice.

Abstract TP407: Effects of Remote Ischemic Conditioning on Cerebral Small Vessel Disease Outcomes

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yuan Wang ◽  
Haiqing Song ◽  
Kai Dong ◽  
Ran Meng ◽  
Shuying Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Flow Velocity ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Control Group ◽  
Vascular Risk ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Vessel Disease

Objective: To evaluate the preliminary efficacy of remote ischemic conditioning (RIC) on patients with cerebral small vessel disease (SVD). Methods: Thirty patients diagnosed with symptomatic SVD within 30 days of onset were enrolled in this prospectively randomized controlled study for 1 year. All patients received routine medical treatment including treating vascular risk factors according to the guideline. Patients in the experimental group (n=14) were administered 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on bilateral upper limbs twice daily for 1 year. Those in the control group (n=16) underwent sham ischemia-reperfusion cycles. Primary outcome was the change of cognitive function measured by mini-mental state examination (MMSE) and montreal cognitive assessment scale (MoCA), and secondary outcomes were changes of plasma biomarkers, cerebral hemodynamic parameters measured by vascular ultrasound and brain lesions measured by MRI FLAIR both at baseline and at the end of 1 year visit. Results: Compared with patients in the control group, patients in the RIC group had higher flow velocity (FV), and lower pulsatility index (PI), but without statistical difference. Patients in the RIC group had improvement in visuospatial and executive abilities (3.86±1.03 vs. 4.43±0.85, p=0.026), reduced plasma triglyceride (1.60±0.74 vs. 1.25±0.38, p=0.019), low density lipoprotein (2.89±0.81 vs. 2.26±0.67, p=0.003) and homocysteine (15.66±10.11 vs. 13.66±9.80 p=0.017). Similarly in the RIC group, the diastolic flow velocity (DFV) of middle cerebral artery (MCA) (right: 33.93±7.67 vs. 36.93±6.12, p=0.032; left: 33.93±7.67 vs. 36.93± 6.12, p=0.032) and the mean flow velocity (MFV) of left MCA (35.00±5.04 vs. 39.50±5.59, p=0.003) increased, and the PI of MCA (right: 1.11±0.19 vs. 1.02±0.14 p=0.030; left: 1.10±0.22 vs. 0.99±0.14, p=0.037) decreased. Conclusion: RIC appears to be potentially effective for improving cognition, enhancing cerebral perfusion, and modifying vascular risk factors in SVD patients. Further studies focusing on long-term neurological outcomes and potential mechanisms underlying RIC on SVD patients are needed.

Association of SUMOlation Pathway Genes With Stroke in a Genome-wide Association Study in India

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012258
Author(s):  
Amit Kumar ◽  
Ganesh Chauhan ◽  
Shriram Sharma ◽  
Surekha Dabla ◽  
P.N Sylaja ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Distribution Width ◽  
A Genome ◽  
Single Marker

Objective:To undertake a genomewide association study (GWAS) to identify genetic variants for stroke in Indians.Methods:In a hospital-based case-control study, eight teaching hospitals in India recruited 4,088 subjects, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed using logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked.Results:Association of vascular risk factors with stroke were similar to previous reports, and show modifiable risk factors like hypertension, smoking, and alcohol consumption having the highest effect. Single-marker based association revealed two loci for cardioembolic stroke (1p21 and 16q24), two for small vessel disease stroke (3p26 and 16p13), and four for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at P<5×10-8. The index SNP of 1p21 is an eQTL (Plowest=1.74×10-58) for RWDD3 involved in SUMOlation and is associated with platelet distribution width (1.15×10-9) and 18-carbon fatty acid metabolism (P=7.36×10-12). In gene-based analysis we identified three genes (SLC17A2, FAM73A and OR52L1) at P<2.7×10-6. 11 of 32 candidate gene loci studied in Indians replicated (P<0.05), and 21 of 32 loci identified through previous GWAS replicated based on directionality of effect.Conclusions:This first GWAS of stroke in Indians identified novel loci and replicated previously known loci. For the first time, genetic variants in the SUMOlation pathway which has been implicated in brain ischemia were identified.

Abstract 224: Increased Total Homocysteine Levels Are Associated With the Risk of Dementia Independently of Cerebral Small-vessel Disease

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kaori Miwa ◽  
Shuhei Okazaki ◽  
Yoshiki Yagita ◽  
Manabu Sakaguchi ◽  
Hideki Mochizuki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Mri Findings ◽  
Vessel Disease ◽  
Cerebrovascular Events ◽  
Multivariable Analyses ◽  
Total Homocysteine

Objectives: Increased serum total homocysteine (tHcy) levels have been associated with not only vascular injury but also dementia. However, given an association between Hcy and vascular injury, such as cerebral small-vessel disease (SVD) or renal impairment, to what extent Hcy would impact future dementia beyond these confouders is unknown. We assessed the predictive value of tHcy levels with the risk of dementia in patients with vascular risk factors, when controlling for the MRI-findings and renal imapirment. Methods: Within a Japanese cohort of partients with vascular risk factors in an observational study from 2001, we evaluated the association between tHcy levels at baseline, defined as a continuous variable (per 1 μmol/L) and as a categorical variable (the tertile of tHcy), the prevalence of MRI-findings, and incident all-cause dementia during follow-up. Baseline brain MRI was used to determine SVD (lacuna, white matter hyperintensities and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy). Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOEε4 allele, educational level, cerebrovascular events, estimated glomerular filtration rate (eGFR), vascular risk factors, and MRI-findings. Results: Of the 643 subjects (mean:67.2±8.4years, male:59%, 12.9±2.6years of schooling), in multivariable analyses adjusted for age, sex, hypertension, cerebrovascular events, eGFR, and intima-media thickness, the highest tHcy tertile (vs lowest) were associated with lacuna, CMBs and strictly deep CMBs, respectively. During the mean 7.3-year follow-up (range:3-13), 47 incident dementia patients (Alzheimer’s disease:24; vascular dementia:18; mixed-type:3; other:2) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, eGFR, and MRI-findings, tHcy level or the highest tertile of tHcy for all-cause dementia remained significant, respectively (relative risk [RR]1.09: p=0.02, RR;2.59: p=0.021). Conclusions: Our results provide additional evidence of Hcy that leads to increased susceptibility to the risk of dementia, suggesting that this association may be mediated by independent mechanisms.

P3-190: Cerebrovascular lesions and vascular risk factors in patients with Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_14) ◽  
pp. P522-P522 ◽  
Author(s):  
Ken Nagata ◽  
Takashi Yamazaki ◽  
Daiki Takano ◽  
Tetsuya Maeda ◽  
Yasuko Ikeda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Cerebrovascular Lesions

Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors

2004 ◽  
Vol 34 (1) ◽  
pp. 125-136 ◽  
Author(s):  
R. BALDWIN ◽  
S. JEFFRIES ◽  
A. JACKSON ◽  
C. SUTCLIFFE ◽  
N. THACKER ◽  
...  
Keyword(s):  
Risk Factors ◽  
Executive Function ◽  
White Matter ◽  
Depressive Disorder ◽  
Late Onset ◽  
White Matter Lesions ◽  
Vascular Risk Factors ◽  
Group Differences ◽  
Vascular Risk ◽  
Control Subjects

Background. Late-onset depressive disorder is associated with white matter lesions and neuropsychological deficits that in some studies are linked to a poorer outcome for depression. Some white matter lesions may be vascular in origin. This study investigated the relationship between response or non-response to antidepressant monotherapy and neuropsychological function, structural brain measures and vascular factors.Method. This was a case–control study. Fifty patients with late-onset major depressive disorder (29 who were responders to antidepressant monotherapy and 21 who were not) were compared with 35 non-depressed control subjects. Measures included assessment of vascular risk factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan.Results. After adjustment for depressed mood and medication at evaluation, both patient groups had significantly more impairment compared to control subjects on verbal learning tasks involving immediate or delayed recall. Patients who did not respond to antidepressant monotherapy had significantly poorer performance than controls on tests involving visuospatial ability, language, word recognition and tests of executive function, whereas there were no differences between control subjects and responders. On two tests of executive function (verbal fluency and the Stroop test) non-responders scored significantly worse than responders. There were no significant group differences on MRI measures of atrophy or of white matter lesions apart from a higher periventricular hyperintensity score in non-responders compared to controls. There were no group differences on measures of vascular disease.Conclusion. The results lend support to the emerging evidence that resistance to treatment in late-onset depression may be associated with impaired executive function. Subtle cerebrovascular mechanisms may be involved.

scholarly journals Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention

2009 ◽  
Vol 11 (2) ◽  
pp. 111-128 ◽  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Engagement ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Cerebrovascular Lesions ◽  
Clinical Onset ◽  
Disease Occurrence ◽  
Dementing Disorders

More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's disease has had tremendous impact on the affected individuals, caregivers, and society. The etiological factors, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to the potential risk roles of vascular risk factors and disorders (eg, cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders. The long-term multidomain interventions toward the optimal control of multiple vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer's disease.

scholarly journals Associations of Vascular Risk Factors and APOE Genotype With Perivascular Spaces Among Community‐Dwelling Older Adults

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Anna Laveskog ◽  
Rui Wang ◽  
Davide L. Vetrano ◽  
Lena Bronge ◽  
Lars‐Olof Wahlund ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
White Matter ◽  
Magnetic Resonance ◽  
Orthostatic Hypotension ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Perivascular Spaces ◽  
Vascular Risk ◽  
Vessel Disease

Background Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults. Methods and Results This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity. Conclusions This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.

Abstract W MP58: The Relationship Between Carotid Stiffness, Diastolic Diameter, and White Matter Hyperintensity Volume: The Northern Manhattan Study

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Matthew S Markert ◽  
Chuanhui Dong ◽  
David Della-Morte ◽  
Eugene Roberts ◽  
Susanne Bartels ◽  
...  
Keyword(s):  
Risk Factors ◽  
White Matter ◽  
Small Vessel Disease ◽  
Vascular Risk Factors ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Large Artery ◽  
Vascular Risk ◽  
Vessel Disease ◽  
Carotid Stiffness

Background: Changes in the extracranial vasculature may be associated with small vessel disease in the brain. We sought to examine the association of carotid stiffness and carotid diastolic diameter with white matter hyperintensity volume (WMHV), a magnetic resonance imaging (MRI) measure for cerebral small vessel disease, in a multi-ethnic community-based cohort. Methods: We evaluated 1140 stroke-free participants in the Northern Manhattan study who underwent brain MRIs and high-resolution carotid ultrasounds. We used linear regression to examine carotid stiffness and diastolic diameter with WMHV after adjusting for sociodemographics, lifestyle behaviors, and traditional vascular risk factors. Results: Among 1140 participants (mean age: 70.6±9.0 years; 61% women; 15% White, 16% Black, 59% Hispanics), the mean carotid stiffness was 8.19 ± 5.39, mean carotid diastolic diameter was 6.16 ± 0.93 mm, and mean WMHV 0.68 ± 0.84. In a fully adjusted model, diastolic diameter was associated with log-WMHV (β=0.10, p=0.001). In a stratified multivariable linear model, greater carotid arterial stiffness and diastolic diameter were associated with log-WMHV among Hispanics (β=0.15, p=0.005 and β=0.13, p<0.001, respectively), but not among blacks or whites. Conclusion: Greater carotid stiffness and diastolic diameter were associated with greater WMHV independent of demographics and traditional vascular risk factors, especially among Hispanics. Further studies are needed to understand how these large artery characteristics relate to WMH formation and lesion load. Carotid ultrasound may be a useful tool to assess the risk of increased brain white matter disease in a pre-clinical stage.

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