Updated: 6/8/2019

Alzheimer Disease

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Snapshot
  • A 78-year-old man presents to his primary care clinic with his wife. He feels well, but his wife is concerned that he has been forgetful. She noticed he had trouble with remembering things over the course of the year. She says that he has been getting lost recently when he goes to the local grocery store. She has noticed that he has become more irritable. He would frequently forget things that were recently told him. Physical examination and laboratory studies are normal. Montreal Cognitive Assessment is 22 out of 30.
Introduction
  • Definition
    • neurodegenerative disorder that is characterized by
      • cognitive decline
        • e.g., dementia
      • difficulty completing activities of daily living
        • e.g., balancing a checkbook, buying groceries, and cooking
      • psychiatric and behavioral issues
  • Epidemiology
    • incidence
      • the most common cause of dementia
    • risk factors
      • increasing age
      • trisomy 21
        • due to amyloid precursor protein being found in chromosome 21  
  • Etiology
    • sporadic (in 95% of cases)
    • apolipoprotein E (APOE) genotype 
      • APOE4 is associated with an increased risk of developing Alzheimer disease (AD)
      • APOE2 is protective against AD
    • presenilin-1 (chromosome 14) and presenilin-2 (chromosome 1) 
      • associated with early-onset AD 
  • Pathogenesis
    • the cause is unclear; however, histopathology demonstrates
      • extracellular amyloid plaques
      • intraneuronal neurofibrillary tangles  
      • altered nucleus basalis of Meynert (a cholinergic nucleus) 
        • prominently affected 
    • gross pathology
      • hippocampal and temporal lobe atrophy
      • hydrocephalus ex vacuo
  • Associated conditions
    • decreased acetylcholine
    • Down syndrome
Presentation
  • Symptoms 
    • impaired declarative episodic memory
      • this is a memory of events that occurred in a specific time and place
    • impaired ability to remember new pieces of information
    • visuospatial and language deficits
    • behavioral and psychological impairment
      • apathy
      • social isolation
      • irritability
Imaging
  • MRI brain
    • findings
      • may demonstrate volume loss in the hippocampus and temporal lobe
Studies
  • Clinical diagnosis
    • rule out reversible causes of dementia (e.g., vitamin B12 deficiency and hypothyroidism)
    • cognitive testing
      • Montreal Cognitive Assessment
      • mini mental status exam
Differential
  • Normal pressure hydrocephalus
    • differentiating factor
      • dementia (wide-based), gait instability, and urinary incontinence
        • diagnosed with improvement of gait after a lumbar puncture
        • managed by a ventriculoperitoneal shunt
  • Vascular dementia
    • differentiating factor
      • a step-wise cognitive decline in the setting of recent stroke significant vascular brain injury on brain imaging
  • Creutzfeldt-Jakob disease
    • differentiating factors
      • rapidly progressive dementia with startle myoclonus 
      • presence of 14-3-3 protein in the cerebral spinal fluid
  • Normal aging
    • differentiating factors
      • preservation of procedural, primary, and semantic memory
      • decreased episodic and working memory
      • decreased executive function
  • Dementia with Lewy bodies
    • differentiating factors
      • visual hallucinations
      • fluctuating cognition
      • parkinsonism
      • REM sleep disorder
      • neuroleptic sensitivity
  • Frontotemporal dementia
    • differentiating factors
      • disinhibition and apathy (in the behavioral variant)
      • aphasia (in the primary progressive aphasia variant)
Treatment
  • Medical
    • cholinesterase inhibitors
      • indication
        • increases cortical cholinergic function and typically used in mild-moderate AD
          • recall that this disease is associated with decreased cortical acetycholine
      • medications
        • donepezil
        • rivastigmine
        • galantamine
    • memantine
      • indication
        • neuroprotective N-methyl-D-aspartate (NMDA) receptor antagonist typically used in moderate-severe Alzheimer disease
          • believed that neuronal excitotoxicity plays a role in the development of AD
Complications
  • Difficulty with eating or refusal to eat
  • Infection
 

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Questions (6)
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

5%

(3/64)

2

Abnormal protein metabolism

59%

(38/64)

3

Hormone deficiency

3%

(2/64)

4

Premature degradation of a protein

28%

(18/64)

5

Nutritional deficiency

5%

(3/64)

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

67%

(116/172)

2

Clumps of alpha-synuclein and ubiquitin protein in neurons

4%

(7/172)

3

Multiple, scattered ischemic lesions in the cortex

3%

(6/172)

4

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

10%

(18/172)

5

Many round vacuoles in the gray matter consistent with spongiform changes

9%

(16/172)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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