Dementia

See also

Definitions

Dementia
1. Chronic loss of previously acquired mental function, including impaired memory, judgment, attention span and problem solving
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

Epidemiology

Prevalence (U.S.)
1. Age 65 to 74 years: 5%
2. Age 75 to 84 years: 13%
3. Age >85 years: 33%

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

Causes

See Dementia Causes

Risks Factors
Alzheimer's Disease

Age >65 years old (greatest risk factor)
Apo E4 Allele
1. Confers 8% risk if two Alleles
Family History of Alzheimer's Disease
FAD gene
Female gender
Low education
Head Trauma
Cardiovascular disease (e.g. prior Myocardial Infarction)
Cerebrovascular Disease (e.g. prior Cerebrovascular Accident)
Diabetes Mellitus
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]

Types
Presentations

Cortical (e.g. Alzheimer's Disease): 60-70% of cases
1. Short Term Memory loss
2. Aphasia
3. Apraxia
Subcortical (e.g. Vascular Dementia): 10-20%
1. Mental slowing
2. Mood disturbance
Metabolic Dementia (e.g. Vitamin B12 Deficiency)
1. Similar presentation as subcortical Dementia
Lewy Body Disease (7%)
1. Parkinsonian symptoms with Dementia
Frontotemporal Dementia
1. Socially inappropriate and compulsive behaviors
2. Empathy loss, change in political and religious beliefs
3. Progressive Aphasia
Mixed Dementia (10-20%)
1. Combined Cortical and subcortical
2. Usually Alzheimer's with Multi-infarct Dementia

Types
Dementia Syndromes

Alzheimer's Disease (60-70%)
Dementia with Lewy Bodies (15-25%)
Frontotemporal Dementia (5-15% overall, but 60% in those 45-60 years old)
Vascular Dementia (5-20%)
Creutzfeldt-Jakaob Disease (<1%)

Criteria

Insidious, gradual onset (months) of deterioration
1. Mild to severe fluctuations
2. All higher cortical functions
Long duration of symptoms
Normal Level of Consciousness, but altered content
1. Impaired memory and
2. One higher cortical function (e.g. Judgement)
Vital Signs typically normal

Presentations
Early

New information is difficult to learn and retain
Complex tasks are difficult to perform
Unable to solve simple problems
Getting lost in familiar surroundings
Difficulty expressing oneself
Irritable or aggressive behavior

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

Findings
Signs and symptoms

Normal alertness, awareness, attentiveness
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

Evaluation
Dementia Screening Tools

See Mental Status Consolidated Screening
Mini-Cognitive Assessment Instrument
1. Patient repeats and recalls 3 unrelated words, and draws a clock face with a given time
General Practitioner Assessment of Cognition (GPCOG)
1. https://www.alz.org/documents_custom/gpcog(english).pdf
Ascertain Dementia 8-Item Informant Questionnaire
1. https://www.alz.org/documents_custom/ad8.pdf
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

Evaluation
Dementia Diagnosis Tools

See Mental Status Exam (lists all tests, history, exam)
St. Louis University Mental Status (SLUMS)
1. http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf
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
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

Evaluation
Depression Screening Tools

Patient Health Questionaire 9 (PHQ-9)
Zung Depression Rating Scale
Cornell Scale for Depression in Dementia
Geriatric Depression Scale (GDS, also in short version)

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
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
Evaluation only as indicated
1. Syphilis Serology (VDRL or RPR)
2. Urinalysis
3. Serum Magnesium
4. Arterial Blood Gas (ABG) or Venous Blood Gas (VBG)
5. Medication Levels
6. Chest XRay
7. Electrocardiogram (EKG)
8. Electroencephalogram (EEG)
  1. Seizure Disorder
  2. Creutzfeldt-Jakob Disease (or other Prion Disease)
9. Lyme Titer
10. Lumbar Puncture for 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
11. Heavy Metal screening
12. Ceruplasmin for Wilson' Disease
13. Arylsulfatase for metachromatic leukodystrophy
14. Serum Protein Electrophoresis for Multiple Myeloma
15. Human Immunodeficiency Virus (HIV)
16. 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
17. Urine Toxicologic screen
18. Urine porphobilinogens

Labs
Alzheimer Disease Specific Testing

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
2. CT Head
  1. Poor Test Sensitivity in Dementia
  2. Evaluates for Intracranial Mass, Intracranial Hemorrhage, large CVA
3. Amyloid Positron Emission Tomography (PET) Scan
  1. Indicated if definitive diagnosis will impact management
  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
Psychosis
Major Depression
Medications are a very common cause
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)

Course

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

Management

See Dementia Management

Management
Neurology Consultation Indications

Rapidly progressive Dementia (weeks to months)
Dementia in a young patient
Severe behavior 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

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