Dementia

See also

Definitions

Dementia
1. Chronic loss of previously acquired mental function (e.g. memory, judgment, attention span, problem solving)
2. Decline in at least 1 of 6 cognitive domains (attention, Executive Function, language, memory, motor, social)
3. Delirium and other Dementia Differential Diagnosis excluded
4. Dementia interferes with Instrumental Activities of Daily Living (IADLs)
Alzheimer's Disease
1. Progressive, uniformly fatal, neurodegenerative disease of the brain with gradual development of Dementia
2. Typical onset after age 60 and associated with severe cortical atrophy, senile Plaques, neurofibrillary tangles
Mild Cognitive Impairment
1. As with Dementia, decline in at least 1 of 6 cognitive domains
2. However, unlike Dementia, does not interfere with Instrumental Activities of Daily Living (IADLs)

Epidemiology

Prevalence (U.S.)
1. Age 65 to 74 years: 5%
2. Age 75 to 84 years: 13%
3. Age >85 years: 33%
Gender
1. Women have higher lifetime Dementia risk from age 45 years (20%, compared with 10% in men)

Pathophysiology
Alzheimer's Disease

Gradual accumulation of amyloid Plaques and neurofibrillary tangles (hyperphosphorylated Tau Proteins)
Neurofibrillary Tangles lead to Neuron degeneration, cerebral atrophy, Memory Loss, overall functional decline

Risk Factors

Dementia
1. Age >65 years old (greatest risk factor)
2. Traumatic Brain Injury
3. Low education
4. Smoking
5. Excessive Alcohol >12 U.S. units/week (one unit =12 oz beer or 5 oz wine)
6. Physical inactivity
7. Sensory loss (Hearing Loss, untreated Vision Loss; also in the Dementia Differential Diagnosis)
8. Obesity
9. Air Pollution
10. Diabetes Mellitus (esp. uncontrolled)
11. Health disparities and social disadvantages
  1. Disproportionately affects black and hispanic patients
12. Cardiovascular disease (e.g. prior Myocardial Infarction)
13. Cerebrovascular Disease (e.g. prior Cerebrovascular Accident)
14. Combined CV factors in middle age (Odds Ratio 3.5)
  1. Hyperlipidemia
  2. Hypertension (increased systolic Blood Pressure)
  3. Kivipelto (2001) BMJ 322:1447-51 [PubMed]
Alzheimer's Disease
1. Most of risk factors for Dementia apply
2. Family History of Alzheimer's Disease
3. Apo E4 Allele
  1. Confers 8% risk if two Alleles
  2. Test Specificity 84% for Alzheimer Disease in late onset Dementia
4. FAD gene
References
1. Livingston (2024) Lancet 404(10452): 572-628 [PubMed]

History

Family members should accompany patient to appointment, sitting side-by side with patient
First ask questions of patient "why are you here?"
1. Do not spend much time on this aspect
2. Establish relationship with patient and establish reliability as historian
Ask family (and patient if mild Dementia)
1. Baseline functional status (education level, work responsibilities)?
2. When was the first time their thinking and memory was completely normal?
3. Timeline of cognitive function loss since onset?
4. Is there any time you thought they were having a stroke?
5. Do they repeat? misplace? Forget names? Rely more on notes and calendars?
6. Who is in charge of medications? Bill Paying? checkbook balancing (IADLs) ?
7. Word finding difficulty?
8. Get lost driving?
9. Do you feel comfortable leaving them alone? Overnight? For a weekend? for a week?
10. Can they perform Activities of Daily Living (ADLs)?
11. Are they depressed? anxious? agitated or restless?
12. Do they have Hallucinations?
13. How is sleep? Do you sleep in the same bed? Nighttime Incontinence?
14. Has there been Head Trauma?
References
1. McCarten (2009) UMN CME Internal Medicine Review, Minneapolis

Exam

Complete set of Vital Signs
Complete Physical Exam (esp. cardiovascular exam)
Comprehensive Neurologic Exam (with Mental Status Exam)
Vision Screening
Hearing screening

Symptoms

Early Presentations
1. New information is difficult to learn and retain
2. Complex tasks are difficult to perform
3. Unable to solve simple problems
4. Getting lost in familiar surroundings
5. Difficulty expressing oneself
6. Irritable or aggressive behavior
Timing
1. Insidious, gradual onset (months to years) of deterioration
2. Long duration of symptoms
  1. Sudden onset and progression over weeks to months suggests alternative diagnosis (see below)
Severity
1. At least one cognitive domain is affected
2. May affect all higher cortical functions in severe cases
3. Mild to severe fluctuations may occur

Signs

Vital Signs are typically normal in routine Dementia presentations
Normal alertness, awareness, attentiveness
1. Content is impaired (Memory Loss and at least one cortical function)
No Hallucinations or Delusions
Disorientation
Memory Impairment (short much more than long term)
1. New forgetfulness
2. Difficult word finding
Impaired Executive, Social, or cognitive function
1. Driving difficulties or getting lost
2. Neglect of self care and household chores
3. Difficult money handling
4. Work mistakes
5. Judgement and Language impaired
Behavior changes
1. See Behavior Problems in Dementia
Personality change
1. Inappropriately friendly or even flirtatious
2. Affect shallow or blunted or social withdrwal
3. Frustration to explosive spells
Psychiatric symptoms
1. Suspiciousness or paranoia
2. Withdrawal or apathy
3. Abnormal beliefs or Hallucinations
Provocative Factors
1. Acute illness
2. Hospitalization
3. Minor surgery
4. Bereavement

Types
Dementia Syndromes

See See Dementia Causes
Alzheimer's Disease (40% up to 60-70%)
1. Most common in women age>65 years
2. CNS accumalation of beta-amyloid Plaque and hyperphosphorylated Tau Protein
3. Cortical Dementia with Short Term Memory loss, Aphasia and Apraxia
  1. Starts with episodic verbal memory Impairment
4. MRI may show volume loss in Hippocampus, Amygdala and temporoparietal regions in advanced disease
5. Life Expectancy: 4 to 8 years
Vascular Dementia (10-20%)
1. Most common in men age >65 years
2. Subcortical Dementia with step-wise progressive mental slowing and mood disturbance
3. Cardiovascular Risks predominate (e.g. Atrial Fibrillation, Hypertension, Hyperlipidemia, diabetes, Tobacco)
4. MRI may show Lacunar Infarcts, encephalomalacia
Dementia with Lewy Bodies or Parkinson Disease Dementia (7%)
1. Most common in men age >70-85 years
2. Parkinsonian symptoms with Dementia, starting with Memory Loss
3. Associated with Daytime Somnolence, prolonged staring, Disorganized Speech, Visual Hallucinations
4. MRI may show diffuse CNS atrophy in advanced disease
Frontotemporal Dementia (1%)
1. Uncommon Dementia with premature age of onset
2. Socially inappropriate and compulsive behaviors, and progressive Aphasia
3. Empathy loss (with change in political and religious beliefs)
4. MRI may show frontal and anterior temporal volume loss in advanced disease
Mixed Dementia (10-20% up to 40%)
1. Combined cortical (Alzheimer's ) and subcortical (multi-infarct) Dementia
Metabolic Dementia (e.g. Vitamin B12 Deficiency)
1. Similar presentation as Vascular Dementia (subcortical Dementia)
Creutzfeldt-Jakob Disease (<1%)
1. Sporadic Creutzfeldt-Jakob Disease (>80% of U.S. cases)
  1. Most common course is rapidly progression Dementia with Myoclonus and variable Ataxia
2. Genetic Creutzfeldt-Jakob Disease (10-15% of U.S. cases)
  1. Most common PRNP Mutation is E200K (Sephardic Jews in Libya and Tunisia, Slovokians)
  2. Rapidly progressive Dementia and Ataxia with onset ages 30 to 55 years old
3. Acquired (rare, <1% of U.S. CJD cases)
  1. Iatrogenic Creutzfeldt-Jakob Disease Causes (e.g. GH injection, Blood Transfusion, neurosurgery)
  2. Variant Creutzfeldt-Jakob Disease (vCJD, Outbreak in UK of BSE 1988-2005)

Evaluation
Screening

Positive screening should prompt use of more extensive Dementia diagnostic tools below
Indications
1. Cognitive Impairment concerns by patient, family, Caregivers, employers or other close contacts
  1. Patient report of Cognitive Impairment has a Likelihood Ratio of 6.5
  2. Family report of Cognitive Impairment increases Dementia likelihood further
2. Universal Screening
  1. CMS recommends screening age >=65 years at annual wellness visits
  2. USPTF does not recommend routine screening in asymptomatic adults (insufficient evidence)
  3. AAN recommends screening patients at risk with validated tools
Dementia Screening Tools
1. See Mental Status Consolidated Screening
2. Quick Dementia Rating System (QDRS)
  2. Rating by Caregivers with 10 question survey (each answered on scale of 0-none to 3-severe)
  3. Mild Cognitive Impairment: 2-5
  4. Dementia: >5 (moderate 13-20, severe 20-30)
3. Mini-Cognitive Assessment Instrument
  1. Patient repeats and recalls 3 unrelated words, and draws a clock face with a given time
4. General Practitioner Assessment of Cognition (GPCOG)
  1. https://www.alz.org/documents_custom/gpcog(english).pdf
5. Ascertain Dementia 8-Item Informant Questionnaire
  1. https://www.alz.org/documents_custom/ad8.pdf
6. Early Detection and Screen for Dementia (NTG-EDSD)
  1. https://www.the-ntg.org/ntg-edsd
  2. Indicated in adults with Down Syndrome or other congenital intellectual disabilities
7. Memory Impairment Screening (MIS)
  1. https://alzfdn.org/wp-content/uploads/2017/08/5-MIS.pdf
Major Depression Screening Tools (screen for depression concurrent with Dementia Screening)
1. Patient Health Questionaire 9 (PHQ-9)
2. Zung Depression Rating Scale
3. Cornell Scale for Depression in Dementia
4. Geriatric Depression Scale (GDS, also available in short version)
Functional Screening
1. Activities of Daily Living Scale (Katz ADL Scale)
2. Instrumental Activities of Daily Living (Lawton IADL Scale)

Evaluation
Dementia Diagnosis Tools

See Mental Status Exam (lists all tests, history, exam)
St. Louis University Mental Status (SLUMS)
1. https://www.slu.edu/medicine/internal-medicine/geriatric-medicine/aging-successfully/assessment-tools/mental-status-exam.php
Addenbrooke's Cognitive Examination (ACE)
1. Differentiates Alzheimer's from other Dementias
2. Detect early Dementia
Mini-Mental Status Exam (requires payment for use)
1. Standard decline 3 points per 6 months
2. Error is +/- 3 points
Montreal Cognitive Assessment
1. http://dementia.ie/images/uploads/site-images/MoCA-Test-English_7_1.pdf
Rowland Universal Dementia Assessment Scale (RUDAS)
1. https://www.dementia.org.au/professionals/assessment-and-diagnosis-dementia/rowland-universal-dementia-assessment-scale-rudas
Psychometric Testing
1. Test of higher cognitive functioning
  1. Logical, abstract, conceptual and verbal reasoning
  2. Identifies more subtle changes in cognition
2. Indications
  1. Early Dementia
  2. Depression
  3. Alcohol Abuse versus Alzheimer's Disease
  4. Unusual Dementias
  5. Non-english speaker or patient with less education

Diagnosis

See Dementia Diagnosis

Associated Conditions

Gait Apraxia
Disinhibited behavior
Slurred speech if Vascular
Anxiety, mood, and sleep disturbance
Delusions and Visual Hallucinations
Speech rambling, irrelevant, and incoherent
Personality change

Labs
Secondary Cause Evaluation

Goals: Rule out reversible cause (Delirium Causes)
Guidelines vary based on organization
1. American Academy of Neurology (AAN)
2. Canadian Consensus Conference on Dementia (CCCD)
Standard Evaluation (most patients)
1. Thyroid Stimulating Hormone (AAN, CCCD)
2. Serum Vitamin B12 Level (AAN)
3. Complete Blood Count (CCCD)
4. Comprehensive Metabolic Panel
  1. Serum Electrolytes
  2. Serum Calcium
  3. Serum Glucose
  4. Liver Function Tests
  5. Renal Function Tests
Lumbar Puncture Indications (rapidly progressive Dementia)
1. Systemic signs and symptoms
2. Atypical presentation
3. Cancer
4. Hydrocephalus
5. Infectious disease
  1. Neurosyphilis
  2. HIV Infection
  3. Cerebral Lyme Disease
  4. Creutzfeldt-Jakob Disease (or Prion Disease)
    1. Positive CSF for 14-3-3 Protein
Electroencephalogram (EEG) Indications
1. Seizure Disorder suspected
2. Creutzfeldt-Jakob Disease (or other Prion Disease)
Other Lab evaluation only as indicated
1. Toxic-Metabolic and Nutritional
  1. Thiamine Level (Vitamin B1, or replace empirically for those at risk)
  2. Serum Magnesium
  3. Serum Folate
  4. Arterial Blood Gas (ABG) or Venous Blood Gas (VBG)
  5. Medication Levels
  6. Heavy Metal screening
  7. Ceruplasmin for Wilson' Disease
  8. Urine Toxicologic Screen
  9. Urine porphobilinogens
  10. Arylsulfatase for metachromatic leukodystrophy
  11. Serum Protein Electrophoresis for Multiple Myeloma
2. Cardiovascular and Pulmonary
  1. Chest XRay
  2. Electrocardiogram (EKG)
3. Infection
  1. Urinalysis
  2. Syphilis Serology (VDRL or RPR)
  3. Human Immunodeficiency Virus (HIV)
  4. Lyme Titer
4. Connective Tissue Disease
  1. Erythrocyte Sedimentation Rate (ESR)
  2. C-Reactive Protein (C-RP)
  3. Antinuclear Antibody (ANA)
  4. C3 Complement
  5. C4 Complement
  6. Anti-DS DNA

Labs
Alzheimer Disease Specific Testing

Precautions
1. Avoid in Mild Cognitive Impairment (poor predictive value for Dementia development)
Apolipoprotein E (not recommended)
PrecivityAD
1. Marketed for age 60 years old and older with Cognitive Impairment
2. Combines 2 tests
  1. Apolipoprotein E (apoE) Genotype
  2. Amyloid-Beta (Abeta) Peptides: Abeta 42 to Abeta 20 ratio
3. Generates a proprietary Amyloid Probability Score
  1. Low Likelihood <36
  2. Intermediate Likelihood 36 to 57 (consider Amyloid PET)
  3. High Likelihood >57
4. References
  1. Anderson (2022) Am Fam Physician 105(1): 79-81 [PubMed]
Lumipulse G
1. Marketed for age 55 years old and older with Cognitive Impairment
2. Measures multiple biomarkers for Alzheimer Disease in cerebrospinal fluid (CSF)
  1. Total and Phosphorylated Tau
  2. Amyloid-Beta (Abeta) Peptides: Abeta 42 to Abeta 40 ratio
    1. Low ratio <0.072 supports Alzheimer Disease diagnosis
3. References
  1. Lau (2023) Am Fam Physician 107(5): 550-1 [PubMed]

Imaging

Imaging modalities
1. Brain MRI (preferred): Especially coronal views
  1. Hippocampal atrophy is hallmark of Alzheimers Disease
  2. Regions of brain atrophy may differentiate Dementia types
  3. MRI is often normal in early disease (e.g. Mild Cognitive Impairment, mild Dementia)
2. CT Head
  1. Poor Test Sensitivity in Dementia (MRI is preferred)
  2. Evaluates for Intracranial Mass, Intracranial Hemorrhage, large CVA
3. Amyloid Positron Emission Tomography (PET) Scan (or FDG-PET Scan)
  1. Indicated if definitive diagnosis will impact management
    1. Unexplained Mild Cognitive Impairment
    2. Atypical Dementia presentations
    3. Early onset Dementia
    4. Planned therapy with Anti-Amyloid Beta Plaque Monoclonal Antibody
  2. Cost is $5000 in 2022 (may be covered by Medicare)
  3. Good efficacy in comparison with autopsy confirmed Alzheimer Disease
    1. Test Sensitivity: 91%
    2. Test Specificity: 92%
Imaging Indications (indicated in most cases of Dementia)
1. Age under 60 years old
2. Dementia with duration under 1 month
3. Rapid progression over months
4. Recent Head Trauma
5. History of Cerebrovascular Accidents
6. History of cancer
7. History of Anticoagulant use
8. Seizure Disorder
9. Urinary Incontinence of new onset
10. Headaches
11. Focal neurologic findings
12. Visual Field Defects
13. Papilledema
14. Gait Abnormality or Ataxia
References
1. Chertkow (2001) Can J Neurol Sci 28:S28-41 [PubMed]
2. Dietch (1983) West J Med 138:835 [PubMed]

Diagnostics
Special Tests (Research use only currently)

Cerebrospinal Fluid for Alzheimer's specific Proteins
1. High tau
2. Low Beta-Amyloid
Functional imaging
1. SPECT scan
2. Positron Emission Tomography (PET Scan)
3. Functional Head MRI

Differential Diagnosis

See Dementia Differential Diagnosis
See Altered Level of Consciousness
Delirium
1. Especially if recent hospitalization or illness
2. In contrast to Dementia, Delirium affects Level of Consciousness and alertness
  1. These findings may also complicate severe Dementia (see Behavior Problems in Dementia)
  2. Altered sleep-wake cycle
  3. Hallucinations
  4. Delusions
  5. Agitation
  6. Emotional Instability
Psychosis
Common causes of Cognitive Impairment
Sensory Loss that may be confused with Cognitive Impairment
1. Hearing Loss
2. Vision Loss
Medications are a common cause of Cognitive Impairment
1. See Drug Induced Altered Level of Consciousness Causes
2. See Polypharmacy
3. See Medication Use in the Elderly (Beers List, STOPP)
4. Anticholinergic Medications (e.g. Elavil, Benadryl)
5. Drug Toxicity (e.g. Digoxin, Phenytoin)
Rapid cognitive decline over weeks to months suggests alternative diagnosis
1. See See Dementia Differential Diagnosis
2. Vascular disorders
3. Acute infection
4. Iatrogenic causes (e.g. medications as above)
5. Neoplasm
6. Metabolic causes

Course

Cases due to reversible cause: 10-20%
High index of suspicion for reversibility in elderly

Management

See Dementia Management

Management
Neuropsychiatric Assessment Indications

Inconclusive Dementia evaluation
Consultation for individualized treatment or rehabilitation recommendations
Differentiate Dementia from the Dementia Differential Diagnosis (including psychiatric disorders)
Evaluate driving safety
Evaluate decision making capacity
Evaluate fitness for duty in the workplace

Management
Neurology Consultation Indications

Rapidly progressive Dementia (weeks to months)
Dementia in a young patient (age <60 to 65 years)
Severe behavioral psychiatric abnormalities
Red Flags for uncommon Dementia
1. Significant personality change
2. Extrapyramidal signs
3. Rapid progression
4. Gaze Palsy
5. Urinary Incontinence
6. Gait Abnormality
7. Visual Hallucinations (Lewy Body Dementia)

Management
Evaluate the Caregivers - Family journey phases

Prediagnostic: Is there a real issue?
Diagnosis: Tramua of the diagnosis
Role changes: Taking away rights
Chronic caregiving: Engulfment and exhaustion
Shared care: Obtaining respites
Long term care: Patient is moved to long-term care
End of life: Prolonging life versus a good death
Reference
1. Caron (2000) Alzheimer's Disease - The Family Journey, North Ridge Press, Plymouth, MN

Resources

See Dementia Resources

References