Introduction

Binswanger's disease, also known as subcortical vascular dementia, is caused by widespread, microscopic areas of damage to the deep layers of white matter in the brain. This damage is the result of atherosclerosis (thickening and hardening of the walls of the arteries), reducing blood flow within the brain. It typically affects older adults and is associated with high blood pressure, stroke, and other vascular conditions.¹

Commonly, Binswanger’s disease is accompanied by mood disorders such as depression, anxiety and bipolar, exacerbating cognitive decline and emotional instability in patients. The occurrence of such comorbid conditions complicates the treatment process, increasing the overall burden on the patient, caregiver and healthcare resources.     

This article provides an overview of the aetiology and manifestation of Binswanger’s disease as well as some comorbid mood disorders. Understanding the existing pathophysiology linking both disorders provides a comprehensive understanding of nuances in its clinical presentation, as well as formulating effective and individualized treatment regimens that address both medical outcomes and improve well-being.  

An Overview of Binswanger’s Disease 

Patients with Binswanger’s disease commonly exhibit a range of medical, physical, and cognitive disturbances. Some of the common symptoms can be grouped into the following categories:²

• Motor symptoms: muscle weakness, exaggerated reflex/hyperreflexia, mild parkinsonism (bradykinesia, tremors, rigidity), issues in maintaining balance, excessive falls, ataxia (coordination and fine motor tasks)
• Cognitive impairment: Decline in executive functioning (troubles with planning, organization, problem-solving, requiring additional mental effort in decision making), problems with processing speed, deficits in attention (focus) and memory (particularly in the later stages)
• Behavioural: Some of the most common behavioural deficits and psychiatric symptoms observed include depressive behaviours, reduced interest, diminished emotional expression (bluntness and apathy)

Some of the imaging features which resulted in advanced diagnostics over the years (seen through FLAIR, T2, MR Angiogram and Susceptibility Weighted Imaging) include:

• Brain atrophy – loss of neurons and overall reduction in brain volume, characteristic across varied types of dementia, particularly within the subcortical regions (responsible for cognitive and motor symptoms in Binswanger’s)
• White Matter Hyperintensities: Areas of the brain with increased signal intensity on T2 MRI images, formed due to small-vessel disease affecting white matter. This is one of the hallmark imaging biomarkers and signs of vascular pathology and contributes to cognitive decline
• Intracranial Atherosclerosis: Atherosclerosis is one of the most common co-occurring conditions in diseases affecting the brain and heart. It is marked by an excessive build-up of plaque within the arteries of the brain, which causes damage to blood vessels and interrupts blood flow
• Microbleeds & Lacunar Artifacts: Some of the small yet crucial markers and indicators for Binswanger’s disease are microbleeds and lacunar artefacts. The former appears as small dots on a Susceptibility-weighted MRI, indicating pathology in a microvascular space. The latter refers to lesions that penetrate arteries, which are linked to cognitive impairment and impair structural and functional connectivity

Mood Disorders in Binswanger’s Disease 

In elderly patients, particularly those diagnosed with variants of Subcortical Ischemic Vascular Dementias, neurocognitive and mood disorders are a common occurrence. For instance, this case study³ discusses a 71-year-old man diagnosed with Binswanger Disease, who also presented with symptoms associated with late-onset bipolar disorder. Some of the psychiatric symptoms exhibited were aggressive behaviour suicidal ideation, impulsivity and irritability. Over the next two months, his condition deteriorated significantly, and the patient showed chronic low moods and homicidal thoughts. His mental state was further compromised due to alcohol intake, non-compliance to medication hypertension, and substance abuse disorders. Further testing revealed a shuffling gait. Neuroimaging tests confirmed what looked like lesions and WM hyperintensities, suggestive of Binswanger Disease, with microbleeds in the right temporo-occipital regions.

Further research also highlights apathy as a key symptom related to dysfunction observed in the subcortical regions, particularly the basal ganglia, pre-frontal and orbitofrontal cortex. A study⁴ presented the significance of assessing gait and apathy in patients with vascular diseases. Over 5 years, there was an observable decline in equilibrium and apathy with disease progression, further exacerbated by pharmacological treatments. Symptoms related to disturbances in mood often manifest as depression or apathy. Although characterized by distinct neural pathways, clinical symptoms may overlap. Through pathophysiological observations, there is an overlap between networks affected causing empathy, and regions with infarcts (the thalamus, pons, prefrontal cortex)  

The final case study describes a 49-year-old male patient who presented with memory loss, slurred speech and behavioural fatigue characterized by motor impairments and changes in personality. Along with neuroradiological testing and clinical evaluations, the patient reported a history of a seizure, microbleeds and a pseudoaneurysm in the right vertebral artery, and was diagnosed with subcortical vascular dementia with chronic hypertension.⁵

Such case studies underscore the importance of neuropsychological and psychiatric evaluations with neurological disorders, and complexities in formulating effective individualized treatment plans. As demonstrated through all cases above, some of the most effective treatment regimens involve controlling blood pressure, managing cardiovascular health and mood stabilizers to combat neurological and psychological health. 

Mechanisms linking Mood Disorders to Binswanger’s Disease 

• Biological: Binswanger’s disease is typically characterized by changes in the brain structure and white matter, affecting the prefrontal and subcortical regions. These areas are responsible for emotional regulation, and recurring small vessel disease causes neurochemical alterations which exacerbate cognitive decline.⁶ Some of the other symptoms notably observed in patients with BD also include obsessive-compulsive tendencies and hypochondriacal preoccupations. It is suggested that the observance of non-ego dystonic obsessional behaviours (repetitive behaviours but not causing any distress, merged with their sense of self and routine) could be a key difference between Binswanger’s and other types of dementia, calling for more studies with increased statistical power.⁷
• Psychological mechanisms: Mood disorders and cognitive decline in vascular diseases such as Binswanger’s further promote symptoms such as depression and anxiety. Due to the progressive nature of the disease as well as a perceived sense of illness, such disorders impact a patient’s self-esteem and overall well-being. Moreover, chronic illness heightens stress levels, weakening immune systems and lowers the ability to adapt to newer limitations and life circumstances. The comorbid nature of Binswanger’s and mood disorders also places increased stresses on caregivers to manage the medical and psychological states of patients, as well as clinicians and healthcare systems in facilitating an effective diagnosis and treatment plan. Patients are also at risk of developing feelings of social isolation, loneliness and withdrawal from daily activities due to lowered social support and the slow pace of research in understanding and tackling the disorder. 

Challenges & Future Directions

Some of the main challenges in diagnostics, treatment and management of Binswanger’s has to do with identification of symptoms. The similarity or overlap in symptoms across various types of dementias makes it difficult to distinguish, leading to misdiagnosis and inappropriate treatment plans. Moreover, medications prescribed to treat comorbid mood disorders have adverse effects, which may not be reported or lead to newer health issues.

A study⁷ evaluated the various biomarkers instrumental in diagnosing Binswanger’s. Some of the main biomarkers included levels of blood-brain-barrier permeability, hyperintensities on MRI and MR Spectroscopy metabolite levels, and elevated album ratios. Moreover, the study also touched on the influences of neuroinflammation as a key marker of progressive Binswanger’s. It was concluded that an effective diagnosis considered MRI findings, neuropsychological testing, clinical history and cerebrospinal fluid analysis.

Another study tested a Transcatheter Intracerebral Laser Intervention to improve blood circulation and promote neurogenesis (cell and tissue regeneration). An improvement in cognitive and psychological functions, along with metabolism, and cerebral blood supply were reported, with clinical effects sustaining over time.

Further research in drug interactions, treatment opportunities, neuroimaging diagnostics and longitudinal studies, along with methodical clinical evaluations are necessary to combat such issues to advance research and treatments in Binswanger’s.⁸

Summary 

• Binswanger’s disease is a form of vascular dementia, characterized by ischemic strokes, white matter hyperintensities and disturbances in gait. More often than not, patients with Binswanger’s disease experience mood disorders such as depression and bipolar, significantly taking a toll on their physical and medical health, and burdening their quality of life
• Studies reveal the cause of mood disorders is not tied to the psychological impact of diagnosis, but an underlying pathophysiological cause linked to Binswanger disease’s mechanisms – the disruption of neural circuits and white matter tracts responsible for mood and emotional regulation, as well as affected subcortical structures
• Diagnosing comorbid conditions is extremely challenging due to the overlapping of symptoms with cognitive decline. Along with existing neuroimaging and CSF evaluations, extensive neuropsychological testing and the use of neuropharmacological & talk-therapy approaches are extremely beneficial in improving a patient’s sense of psychosocial competence and adjustment
• Clinicians and researchers must take into careful consideration the existing treatment regimes and standards of care in diagnosing and treating such conditions. Integrated research and treatment approaches considering both medical and lifestyle issues help clinicians gain a more comprehensive understanding of the clinical presentations of disorders, to craft effective techniques to diagnose, treat and manage mood disturbances and neurological issues in Binswanger’s disease