What are the underlying conditions that can cause dementia?

Underlying Conditions Causing Dementia

Dementia is caused by multiple underlying conditions, with Alzheimer's disease and cerebrovascular dementia being the two most common causes, accounting for 50-75% and 20% of cases respectively, followed by Lewy body disorders (5%) and frontotemporal dementia (5%). 1

Major Causes of Dementia

Neurodegenerative Disorders

• Alzheimer's Disease: The most common cause (50-75% of cases), characterized by amyloid plaques and neurofibrillary tangles 1, 2
• Lewy Body Disorders: Include Parkinson's disease dementia and dementia with Lewy bodies, characterized by alpha-synuclein containing Lewy bodies 1, 3
• Frontotemporal Dementia: Occurs earlier than other forms, progresses rapidly, and often has a genetic component 4

Vascular Causes

• Cerebrovascular Dementia: The second most common cause (approximately 20% of cases), often co-occurring with other forms of dementia 1, 2
• Stroke-related dementia: Can result from focal neurologic damage causing cognitive impairment 1

Potentially Reversible Causes

• Metabolic Disorders: Including hypothyroidism, which can mimic dementia symptoms 1
• Nutritional Deficiencies: Vitamin B12 deficiency is a notable example 1
• Toxic/Nutritional Disorders: Can lead to rapidly progressive dementias 1

Risk Factors for Dementia

Non-modifiable Risk Factors

• Age: The strongest and best-studied risk factor for dementia 1
• Genetics: First-degree relative with Alzheimer's disease, apolipoprotein ε4 genotype, Down syndrome 1

Modifiable Risk Factors

• Cardiovascular Risk Factors: Hypertension, diabetes, midlife obesity increase risk for both Alzheimer's disease and vascular dementia 1
• Lifestyle Factors: Low educational level, head trauma, physical inactivity, smoking, excessive alcohol consumption 1

Less Common Causes

• Infectious/Inflammatory Conditions: Can cause rapidly progressive dementias 1
• Neoplastic and Paraneoplastic Conditions: Brain tumors can cause cognitive impairment 1, 5
• Normal Pressure Hydrocephalus: Characterized by the triad of dementia, gait disturbance, and urinary incontinence 1
• Prion Diseases: Cause rapidly progressive dementias with distinctive features 1

Clinical Implications

• Most dementia cases involve multiple pathologies, particularly in older adults 1, 6
• Only about 1.5% of mild to moderate dementia cases are fully reversible, despite the presence of potentially reversible conditions 1
• Dementia diagnosis requires evidence of cognitive decline affecting at least two cognitive domains (memory, language, visuospatial function, or executive function) 1
• Neuroimaging plays a central role in diagnosis, helping to identify structural causes such as tumors, infarcts, or hydrocephalus 1

Diagnostic Approach

• Thorough clinical history and cognitive assessment are essential, with corroboration from a close friend or family member 6
• Brain imaging is important to identify structural causes and patterns of atrophy 1
• Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical cases (onset before age 65, rapid progression) 6

Understanding the underlying cause of dementia is crucial for appropriate management, as treatment approaches may differ based on etiology, though options remain limited for most neurodegenerative forms 7, 6.