423 Alzheimer's Disease

Question 1

Most common cause of dementia in the elderly

Answer 1

Alzheimer’s disease

Question 2

Major genetic risk for AD

Answer 2

Epsilon 4 allele of the apolipoprotein E gene

Question 3

Characteristic pattern of cognitive changes of AD

Answer 3

Begins with memory impairment and progresses to language and visuospatial deficits, followed by executive dysfunction

Question 4

Describe the following varieties of presentation in AD

Non-memory complaints

Posterior cortical atrophy syndrome

Progressive “logopenic” aphasia

Corticobasal syndrome

Frontal variant

Answer 4

Non-memory complaints
- word-finding, organization, or navigational difficulty

Posterior cortical atrophy syndrome
- visual processing dysfunction

Progressive “logopenic” aphasia
- difficulties with naming and repetition

Corticobasal syndrome
- asymmetric akinetic-rigid-dystonic syndrome

Frontal variant
- dysexecutive/behavioral

Question 5

Mild cognitive impairment (MCI) refers to…

Answer 5

Once the memory loss becomes noticeable to the patient and spouse and falls 1.5 standard deviations below normal on standardized memory tests (~50% of patients with MCI will progress to AD over 4 years)

Question 6

“Prodromal AD” refers to…

Answer 6

A person with biomarker evidence of AD (amyloid imaging positive with positron emission tomography (PET) or low cerebrospinal Abeta42 and mildly elevated tau) in the absence of symptoms

Question 7

Anosognosia refers to…

Answer 7

Unawareness of difficulties in daily activities, such as keeping track of finances, following instructions on the job, driving, shipping, and housekeeping

Question 8

Pattern of language impairment in AD

Answer 8

First naming, then comprehension, and finally fluency

Question 9

Apraxia refers too…

Answer 9

Trouble performing learned sequential motor tasks such as using utensils or appliances

Question 10

Most common cause of death in the end stages of AD

Answer 10

Aspiration

Question 11

Typical duration of symptomatic AD

Answer 11

8-10 years (but the course ranges from 1 to 25 years)

Question 12

Pattern of brain atrophy in typical amnestic AD

Answer 12

Brain atrophy begins in the medial temporal lobes before spreading to lateral and medial parietal and temporal lobes and lateral frontal cortex.

Question 13

CSF findings in AD in terms of

A beta 42

Phosphorylated tau protein

Answer 13

A beta 42 - reduced

Phosphorylated tau protein - elevated

Question 14

TRUE OR FALSE: Slowly progressive decline in memory and orientation, normal results on laboratory tests, and an MRI or CT scan showing only distributed or posteriorly predominant cortical and hippocampal atrophy are highly suggestive of AD.

Answer 14

TRUE

Question 15

Differentials of AD:

Vascular dementia or, rarely, Normal pressure hydrocephalus (NPH)

Parkinson’s disease

Dementia with Lewy bodies

Vitamin B12 deficiency

Metastatic or primary brain neoplasm

Creutzfeldt-Jakob disease

Frontotemporal dementia

Answer 15

Vascular dementia or, rarely, Normal pressure hydrocephalus (NPH) - early prominent gait disturbance with only mild memory loss

Parkinson’s disease - restring tremor with stooped posture, bradykinesia, and masked facies

Dementia with Lewy bodies - early appearance of parkinsonian features in association with fluctuating alertness, visual hallucinations, or delusional misidentification

Vitamin B12 deficiency - loss of joint position and vibration sensibility accompanied by Babinski signs, especially in a patient with a history of autoimmune disease, small bowel resection or irradiation, or veganism

Metastatic or primary brain neoplasm - early onset of a focal seizure

Creutzfeldt-Jakob disease - rapid progression over a few weeks or months associated with rigidity and myoclonus

Frontotemporal dementia - prominent behavioral changes with intact navigation and focal anterior-predominant atrophy on brain imaging

Question 16

Most important risk factors for AD

Answer 16

Age >70 years

Positive family history

Question 17

Other risk factors for AD

Answer 17

Positive family history
Female sex
History of head trauma with concussion
Low educational attainment
Vascular disease and stroke
Diabetes (increases the risk of AD threefold)
Etc

Question 18

The earliest and most severe degeneration at autopsy is usually found in the

Answer 18

Medial temporal lobe (entorhinal/perirhinal cortex and hippocampus), inferolateral temporal cortex, and nucleus basalis of Meynert

Question 19

Characteristic microscopic findings in AD

Answer 19

Neuritic plaques and neurofibrillary tangles

Question 20

Term used to denote soluble amyloid species that may cause cellular dysfunction and represent the early toxic molecule in AD

Answer 20

Oligomers

Question 21

Amyloid angiopathy refers to…

Answer 21

The accumulation of A beta in cerebral arterioles

Question 22

NFTs are composed of…

Answer 22

Silver-staining neuronal cytoplasmic fibrils composed of abnormally phosphorylated tay protein; they appear as paired helical filaments by electron microscopy

Question 23

What is the initiating cause of AD in adult Down’s syndrome which results in excess cerebral amyloid production

Answer 23

Extra dose of the APP gene on chromosome 21

(Adults with trisomy 21 (Down’s syndrome) consistently develop the typical neuropathologic hallmarks of AD if they survive beyonf age 40 years

Question 24

Transmembrane protein from which the A beta protein is derived

Answer 24

Amyloid precursor protein (has neurotropic and neuroprotective properties)

Question 25

AD-causing genes that have been found in large families with multigenerational familial AD

Answer 25

Presenilin-1 (PSEN-1) and Presenilin-2 (PSEN-2)

PSEN-1 - tend to produce AD with an earlier age of onset, and a shorter, more rapidly progressive course than the disease caused by PSEN-2

Question 26

The presenilins are homologous to a cell-trafficking protein, sel 12, found in which nematode?`

Answer 26

Caenorhabditis elegans

Question 27

Mutations in this gene are the most common cause of early-age-of-onset FAD (40-70% of cases)

Answer 27

PSEN-1

Question 28

The gene and allele that confers increased risk of AD

Answer 28

Apo epsilon gene on chromosome 19

Apo epsilon 4 allele

(risk is especially prominent in women)

Question 29

Most important genetic risk factor for sporadic AD that acts as a dose-dependent disease modifier

Single most important biologic marker associated with AD risk

Answer 29

Apo epsilon 4 allele

Question 30

Primary focus in the management of AD

Answer 30

Long-term amelioration of associated behavioral and neurological problems, as well as providing caregiver support

Question 31

Medications approved by the US FDA for the treatment of AD

Answer 31

Donepezil, rivastigmine, galantamine, memantine (all with only modest efficacy for AD)

Question 32

Drug that is no longer used in AD due to hepatotoxicity

Answer 32

Tacrine

Question 33

MOA of donepezil, rivastigmine, and galantamine

Answer 33

Inhibition of cholinesterases, primarily acetylcholinesterase, with a resulting increase in cerebral acetylcholine levels

Question 34

MOA of memantine

Answer 34

Blockage of overexcited N-methyl-D-aspartate (NMDA) glutamate receptors

Question 35

TRUE OR FALSE: Memantine is not approved for mild AD.

Answer 35

TRUE

Question 36

Major side effects of cholinesterase inhibitors

Answer 36

GI (nausea, diarrhea, cramps), altered sleep with unpleasant or vivid dreams, bradycardia (usually benign), muscle cramps

Question 37

Other treatments being studied for AD

Answer 37

Estrogen replacement therapy
Extract of Ginkgo biloba
Vaccination against A beta 42
Beta and gamma secretase inhibitors
Medications that modify tau phosphorylation and aggregation
NSAIDs and statins

Question 38

Drugs commonly used for mild to moderate depression in the early stages of AD

Answer 38

Selective serotonin reuptake inhibitors (due to low anticholinergic side effects, i.e. escitalopram)

Question 39

Treatment for seizure in AD

Answer 39

Levetiracetam

Question 40

Treatment for neuropsychatric symptoms of AD (agitaiton, insomnia, hallucinations, and belligerence)

Answer 40

Newer generation of atypical antipsychotics (risperidone, quetiapine, olanzapine)

Question 41

Medications that should be vigilantly avoided in AD

Answer 41

Medications with strong anticholinergic effects, including sleep aids (diphenhydramine) and incontinence therapies (oxybutynin)