Updated: 3/11/2019

Alzheimer Disease

Topic
Review Topic
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Questions
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Evidence
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Videos
3
Snapshot
  • A 78-year-old man presents to his primary care clinic and is accompanied by his wife. He feels well, but his wife is concerned that he has become more confused over the past few weeks. He enjoys socializing with family and friends, but sometimes has difficulty finding words and recently forgot his niece's name. He walks around his neighborhood for exercise, but has the tendency to wander and get lost. He has a history of hypertension and atrial fibrillation. Current medications are warfarin and dronedarone. Physical exam is unremarkable. Recent lab results were within normal limits. 
Introduction
  • Most common cause of dementia in the elderly
  • Pathogenesis remains unclear, but involves
    • accumulation of neurotoxic proteins, amyloid beta (Aβ-amyloid) and tau
    • ↓ ACh neurotransmission by cholinergic neurons in the nucleus basalis of Meynert 
Causes
  • Majority are sporadic
  • Genetic forms
    • early-onset
      • rare
      • autosomal dominant
      • can involve presenilin mutations 
        • presenilin-1 (chromosome 14)
        • presenilin-2 (chromosome 1)
      • associated with Down syndrome (trisomy 21)
        • ↑ risk of developing Alzheimer's because APP gene is located on chromosome 21  
        • commonly presents before age 40 
    • late-onset 
      • allele variations of apolipoprotein E (APOE) on chromosome 19 affect risk of developing Alzheimer's disease 
        • ε4 is associated with increased risk
        • ε2 is associated with decreased risk
Presentation
  • Progressive symptoms
    • mild
      • short-term memory loss
    • moderate 
      • inability to learn/recall information
      • long-term memory loss
      • wandering
      • mood swings and personality changes including aggression
    • severe
      • incontinence
      • gait disturbance
      • unable to perform ADLs
Evaluation
  • Clinical diagnosis of exclusion
    • confirmation is autopsy histology
  • Characteristic findings on histopathology (see above image):
    • senile/neuritic plaques
      • extracellular Aβ-amyloid core derived from amyloid precursor protein (APP) 
        • APP normally degraded via α-cleavage
        • β-cleavage of APP results in Aβ-amyloid
    • neurofibrillary tangles 
      • intracellular aggregations of hyperphosphorylated tau protein
        • tau is an insoluble cytoskeletal element (microtubule-associated protein)
      • tangles correlate with degree of dementia
    • neuronal degeneration
      • results in diffuse cortical atrophy
      • widening of sulci, narrowing of gyri, expansion of the ventricles
Treatment
  • See Alzheimer's drugs
Prognosis, Prevention, and Complications
  • Complications
    • amyloidosis may result in angiopathy
    • results in weakened vessel walls and can lead to rupture with intracranial hemorrhage
  • Most common cause of death is infection
    • mental status changes associated with sepsis are not detected when superimposed on baseline Alzheimer's disease
 

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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.NE.74) A 40-year-old male with Down syndrome is brought to your clinic by his mother. She reports that over the past few months he has started having difficulty managing his daily routine at his assisted-living facility and no longer seems like himself. She says that last week he wandered away from the facility and was brought back by police. Additionally, he has stopped taking his regular antiepileptic medication, and she is concerned that he might have a seizure. TSH is checked and is normal. Which of the following is most likely to be responsible for this man's current presentation? Review Topic

QID: 100590
1

Expansion of trinucleotide repeats

6%

(1/18)

2

Abnormal protein metabolism

67%

(12/18)

3

Hormone deficiency

0%

(0/18)

4

Premature degradation of a protein

28%

(5/18)

5

Nutritional deficiency

0%

(0/18)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(M1.NE.72) A 38-year-old man with mental retardation (IQ 50), facial features that include epicanthic folds and low-set small ears, and hands pictured in Figure A, is brought in by his elderly parents, who provide constant care. They are concerned that over the past 3 years, he has become increasingly forgetful and less interested in conversing and sharing his thoughts. If a post-mortem brain autopsy were conducted, the most likely histopathological feature in his brain underlying these changes would be: Review Topic

QID: 106502
FIGURES:
1

Beta-amyloid plaques and neurofibrillary tangles of phosphorylated tau

64%

(74/116)

2

Clumps of alpha-synuclein and ubiquitin protein in neurons

6%

(7/116)

3

Multiple, scattered ischemic lesions in the cortex

3%

(4/116)

4

Marked loss of cells in the head of caudate with dilated lateral ventricles

9%

(11/116)

5

Many round vacuoles in the gray matter consistent with spongiform changes

11%

(13/116)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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