Essential Concepts in Dementia: A Comprehensive Guide
Definition and Epidemiology
Dementia is an acquired loss of cognition affecting multiple cognitive domains—including memory, language, attention, visuospatial abilities, and executive function—sufficiently severe to impair social or occupational functioning. 1
- Worldwide, 47 million people live with dementia, with projections reaching 131 million by 2050 1
- In the United States, 5.8 million people have Alzheimer disease, the most common dementia subtype 1
- Dementia affects approximately 5% of those aged 65 years and older, increasing to 20% at age 75 or older 2
- Most dementia cases involve more than one neuropathology, typically Alzheimer disease combined with cerebrovascular pathology 1
Classification of Dementia Types
Degenerative Dementias
- Alzheimer disease (AD): accounts for 50-70% of all dementia cases 3
- Dementia with Lewy bodies (DLB) 3
- Parkinson disease with dementia (PDD) 3
- Frontotemporal lobar degeneration (FTLD) 3
Non-Degenerative Dementias
- Vascular dementia (VaD) 3
- Normal pressure hydrocephalus (NPH) 3
- Dementia from craniocerebral injury, infection, immunity disorders, tumors, poisoning, and metabolic diseases 3
Diagnostic Approach
Initial Clinical Evaluation
Obtain a detailed history from both the patient AND a reliable informant (family member or close friend), specifically focusing on changes in cognition, functional abilities, and behavioral/neuropsychiatric symptoms. 4
Key historical elements to assess:
- Progressive cognitive decline documented through serial assessments increases diagnostic certainty 5
- Onset pattern: gradual versus rapid (rapid onset suggests urgent evaluation) 4
- Age of onset: younger than 65 years is atypical and warrants additional workup 1
- Specific cognitive domains affected: memory, language, visuospatial orientation, executive function 1
- Impact on activities of daily living and social/occupational function 4
- Behavioral and neuropsychiatric symptoms 4
Cognitive Screening Tools
Use MoCA (Montreal Cognitive Assessment) for mild cognitive impairment and mild dementia; use MMSE (Mini-Mental State Examination) for moderate to severe dementia. 4
- MMSE has sensitivity and specificity exceeding 80% for distinguishing elderly patients with dementia 3
- MoCA demonstrates superior sensitivity and specificity compared to MMSE for identifying mild cognitive impairment (MCI) and mild AD 3
- Supplement with structured scales: Clock Drawing Test for cognition, FAQ/DAD/IQCODE for functional assessment, NPI-Q/MBI-C for behavioral symptoms 4
Physical and Neurological Examination
Perform a thorough mental status examination to delineate specific impairments in memory, language, attention, visuospatial cognition, executive function, and mood. 1
- Focal neurologic abnormalities suggest stroke as a contributing etiology 1
- Look for signs specific to dementia subtypes (e.g., parkinsonism in DLB or PDD) 3
Laboratory Evaluation
Core laboratory tests are recommended to identify treatable causes of cognitive impairment. 6
- Basic metabolic panel, thyroid function, vitamin B12 level 6
- Complete blood count 6
- Additional tests based on clinical suspicion (e.g., syphilis serology, HIV testing) 6
Neuroimaging
Brain imaging with CT or MRI is recommended in selected cases to rule out treatable causes (tumor, subdural hematoma, normal pressure hydrocephalus) or to identify cerebrovascular disease. 6
- Structural imaging may demonstrate focal atrophy, infarcts, or tumors not identified on physical examination 1
- Routine functional imaging is not recommended for family physicians 6
Advanced Diagnostic Testing
Consider cerebrospinal fluid assays or genetic testing only in atypical dementia cases: 1
- Age of onset younger than 65 years 1
- Rapidly progressive dementia 4
- Atypical presentations with impairment in multiple cognitive domains but preserved episodic memory 1
- Early-onset dementia 4
Neuropsychological testing should be reserved for cases where clinical assessment is inconclusive (symptoms present but normal examination findings). 1
Treatment Strategies
Non-Pharmacologic Interventions
Non-pharmacologic interventions should be implemented for all dementia patients and, according to Japanese guidelines, should take precedence over pharmacotherapy for behavioral and psychological symptoms of dementia (BPSD). 3
Core non-pharmacologic approaches:
- Cognitive training and cognitively engaging activities (reading, puzzles) 3, 1
- Physical exercise programs, including both aerobic and anaerobic activities 3, 7, 1
- Structured daily routines with consistent wake times, meal times, and bedtime to reinforce circadian rhythms 7
- Socialization activities (family gatherings, group activities) 1
- Music or art therapy 3
- Dietary modifications 3
Environmental modifications:
- Maximize bright light exposure during morning hours; reduce evening light exposure 7
- Reduce evening stimulation: avoid crowded places, excessive noise, household clutter 7
- Use orientation aids: calendars, clocks, color-coded labels 7
Pharmacologic Treatment for Alzheimer Disease
Mild to Moderate AD
Cholinesterase inhibitors (donepezil, rivastigmine, or galantamine) should be considered as first-line pharmacological treatment for mild to moderate Alzheimer disease. 3, 4, 8
Donepezil:
- Start at 5 mg once daily 7, 9
- May increase to 10 mg daily after 4-6 weeks 7, 9
- Demonstrates 1-3 point improvement on ADAS-cog scale 7
- FDA-approved for mild, moderate, and severe AD 9
Rivastigmine:
- Initiate at 1.5 mg twice daily 7
- Increase by 1.5 mg twice daily every 4 weeks as tolerated 7
- Maximum dose: 6 mg twice daily 7
- Also FDA-approved for symptomatic Parkinson disease dementia 1
Galantamine:
- Start at 4 mg twice daily with meals 7
- Increase to 8 mg twice daily after 4 weeks 7
- May increase to 12 mg twice daily based on tolerability 7
Clinical benefits of cholinesterase inhibitors: 8
- Delay clinical decline 3, 8
- Improve cognitive function, memory, thinking 3, 8
- Reduce symptoms such as memory loss and confusion 3, 8
- Improve outcomes across cognition, global clinical function, activities of daily living, and behavioral symptoms 8
Vitamin E:
- Consider vitamin E 1,000 IU orally twice daily to slow AD progression 3
- Has a more favorable risk-benefit ratio than selegiline 3
Moderate to Severe AD
Memantine (alone or combined with a cholinesterase inhibitor) is recommended for moderate to severe dementia, providing cumulative, additive benefits over monotherapy. 7, 10
- FDA-approved specifically for moderate to severe Alzheimer disease 10
- Can be used as add-on therapy to cholinesterase inhibitors 7
Donepezil 23 mg/day:
- For patients already on stable donepezil 10 mg/day for at least 3 months 9
- Demonstrated statistically significant superiority over 10 mg/day on cognitive measures (SIB) 9
- Consider for patients with moderate to severe AD requiring enhanced symptomatic control 9
Treatments NOT Recommended
Estrogen should NOT be prescribed to treat Alzheimer disease. 3
Antipsychotics are contraindicated as first-line treatment due to FDA black box warning for increased risk of death in dementia patients, plus associated risks of falls, stroke, and death. 8
Insufficient evidence supports routine use of: 3
- Other antioxidants (beyond vitamin E)
- Anti-inflammatory agents
- Ginkgo biloba (some benefit possible but evidence lacking) 3
Vascular Dementia Management
Focus on vascular risk factor management and stroke prevention for vascular dementia. 4
- Control hypertension, diabetes, hyperlipidemia 4
- Antiplatelet therapy for stroke prevention 4
- Lifestyle modifications (smoking cessation, exercise, diet) 4
Monitoring and Follow-up
Standard follow-up should occur every 6-12 months for most patients, with more frequent visits (every 3-6 months) for patients with behavioral symptoms or neuropsychiatric dysfunction. 4
Periodically reassess cognitive, functional, neuropsychiatric, and behavioral symptoms to monitor disease progression and adjust treatment. 3, 8
Multi-dimensional tracking should include:
- Cognition (repeat cognitive testing) 4
- Functional abilities (activities of daily living) 4
- Behavioral and neuropsychiatric symptoms 4
- Caregiver burden and support needs 4
Specialist Referral Criteria
Urgent evaluation is warranted for: 4
- Rapidly progressive dementia 4
- Early-onset dementia (age <65 years) 4
- Atypical presentations 4
- Delirium superimposed on dementia 4
Critical Pitfalls to Avoid
Do not delay cholinesterase inhibitor initiation while pursuing extensive workup for reversible causes if the clinical picture clearly suggests Alzheimer disease. 8
Do not use cholinesterase inhibitors as behavioral control agents—their primary benefit is cognitive and functional, not behavioral management. 8
Avoid relying solely on pharmacological approaches without implementing environmental and behavioral strategies, as non-pharmacologic interventions have demonstrated efficacy with minimal risk. 7
Do not prescribe medications with anticholinergic side effects, which can worsen cognitive symptoms. 7
Recognize that all symptomatic therapies for Alzheimer disease do not alter the underlying disease process—patients continue to experience decline over time despite treatment. 7
In patients aged 80 or older, more than one cause of dementia is often present (e.g., AD plus vascular dementia), requiring comprehensive evaluation. 5
Register patients at risk for wandering in the Alzheimer's Association Safe Return Program, as nighttime confusion may lead to wandering. 7
Caregiver Support
After diagnosis, people with dementia and their families should have access to a continuum of services in both community and health facility settings, permeating all aspects of disease management from diagnosis support to end-of-life care. 3