Neurocognitive Disorders

Question 1

What is Dementia/Major Neurocognitive Disorder?

Answer 1

Functional brain syndrome resulting from a broad category of brain diseases or brain injury that result in a significant decline in multiple areas of cognitive functioning and the ability to perform routine ADLs from a previous baseline. Impairments are permanent.

Onset is often insidious

Question 2

What cognitive/behavioral functions are typically affected by dementia?

Answer 2

—Recent episodic (short term) memory
—Receptive/expressive language
—Semantic memory (factual knowledge)
—Executive functions
—Motivation
—Behavioral regulation

Question 3

What are the Clinical Diagnostic requirements for Dementia/Major Neurocognitive Disorder?

Answer 3

—Poor memory + at least 1 other cognitive complaint
—Evidence of impairments on formal testing
—Impairments in routine daily activities like cooking/meal prep, bill paying/financial management, meds management, self care etc

***if only memory is impaired its Amnestic disorder

Question 4

What is Mild Cognitive Impairment?

Answer 4

A transitional stage between normal aging and dementia. Functional brain syndrome in which the onset and progression of cognitive deficits is beyond that expected for an individuals age and level of education, but progress of cognitive deficits is NOT severe enough to impair daily functioning

Question 5

What are the 4 subtypes of Mild Cognitive Impairment?

Answer 5

—Amnestic/Nonamnestic

—Single Domain/Multiple Domain

Question 6

What % of individuals with Mild Cognitive Impairment convert to dementia each year?

Answer 6

13%

Question 7

What are the clinical requirements for a diagnosis of mild cognitive impairment?

Answer 7

—>1 cognitive complaints
—Evidence of impairment on formal testing
—Daily functioning relatively intact

Question 8

How do you assess daily functioning?

Answer 8

Functional Activities Questionnaire FAQ.

—Completed by informant and rates examinees ability to perform activities in 10 functional categories on a 0-3 scale

0=normal
1= has difficulty but does by self
2= requires assistance to complete activity
3=Dependent/unable to perform activity even with assistance

Scores summed 0-30

Clinical cutoff =9
—indicative of functional impairment and possible cognitive impairment

Question 9

Major vs Mild NCD is distinguished based on level of impairment in what 6 cognitive domains?

Answer 9

—Attention
—Executive functions
—New learning and memory
—Language
—perceptual motor abilities
—Social cognition

Question 10

What labs should you get when evaluating for NCDs?

Answer 10

—Routine imaging (CT and MRI)
—BCB
—Serology (B12, HIV, Syphilis)
—Liver and thyroid function tests

Optional:
—Functional imaging (fMRI, PET)
—EEG

Question 11

What is delirium?

Answer 11

Characterized by disturbances of
—Ability to direct, focus, maintain, and shift attention
—Awareness of the immediate environment
—Memory, orientation, and language

Results from direct physiologyical consequences of 
—Medical conditions
—substance intoxication or withdrawal
—exposure to a toxin
—Multiple conditions/exposures

Develops over a comparatively short amount of time (hours to days)

Can be superimposed on a major or mild NCD

Common in hospitals and the elderly and clears/improves once underlying condition resolves

Question 12

What is the most common NCD type?

Answer 12

Neurocognitive disorder due to Alzheimer’s disease

Accounts for 50-70% of neurocognitive disorders

Question 13

What are the risk factors for NCD d/t Alzheimer’s?

Answer 13

—Hx of head injury
—Low education
—Female
—First degree relative with Alzheimer’s
—APOE E4 Gene (codes for apoliprotein E production)

Question 14

What is the Disease course of NCD d/t Alzheimer’s like?

Answer 14

Insidious onset
—initial complaints of poor recent episodic memory
—Forgetfulness and confusion may be more apparent in unfamiliar environments
—Apathy/withdrawal may be present early
—As progresses, other cognitive functions, instrumental ADLs, and insight are affected
—Motor skills and basic sensory functions are NOT affected

Question 15

What is the average survival length of NCD d/t Alzheimers?

Answer 15

8 years from diagnosis at 65

3 years from diagnosis at age 90

Question 16

What neuroanatomical changes do you see in NCD d/t Alzheimer’s ?

Answer 16

Cortical and subcortical atrophy
—Temporal lobes
—Hippocampi
—Temporal parietal association cortex
—Frontal lobes

Dilation/Enlargement of ventricles
—Hydrocephalus ex vacuo

Sultan enlargement

Question 17

What neuro chemistry components do you see in NCD d/t Alzheimers?

Answer 17

Depletion of Acetylcholine.

Apolipoprotein E4 (APOE4) 
—Genetic risk for earlier onset
—E4 single copy= 1.75x risk
—E4 two copies=8x risk

Amyloid Plaques
—Comprised of beta amyloid 42 protein that collects into plaques and causes inflammation and neuronal death

Neurofibrillary tangles
—Comprised of tau proteins in neurons that are atypically folded and result in neuronal death
—NFTs also seen in cases of TBI and FTLD

Question 18

What is Major/Mild Frontotemporal NCD?

Answer 18

Characterized by progressive loss of neurons in frontal and temporal lobes
—NFTs may be present
—Amyloid plaques are rare
—Insidious onset

The peak age of onset is 55-65 and accounts for 20-25% of NCD cases under age 65

Two subtypes
—Behavioral variant
—Language variant

Question 19

What is the survival length post onset of Major/Mild Frontotemporal NCD?

Answer 19

Survival = 6-11 years post onset

Question 20

What is the Behavioral Variant of Major/Mild Frontotemporal NCD?

Answer 20

Characterized by insidious onset behavioral and personality changes and lack of insight.
—Memory and othe cognitive functions are initially preserved

Core behavioral features are:
—Behavioral disinhibition
—Apathy or inertia
—Loss of sympathy or empathy
—Perseverative, stereotyped, compulsive/ritualistic behavior
—Food cravings or hyper-orality

Question 21

What is the Language Variant of Major/Mild Frontotemporal NCD?

Answer 21

Prominent decline in some aspect of language functioning
—Expressive language/speech production
—Word finding problems
—Object naming
—Grammar
—Comprehension of words, objects, concepts

Memory is typically noticeably less affected than language

Visuoperceptual abilities relatively unaffected

Two subtypes:
—Primary progressive aphasia
—Semantic Dementia

Question 22

What is Lewy Body Dementia? (NCD with Lewy Bodies)

Answer 22

Atypical Parkinsonism/Parkinson’s plus disorder
—Progressive supranuclear palsy
—Corticobasal degeneration
—Multiple system atrophy
—Olivopontocerebellar atrophy

It shares features of Parkinson’s Disease and Alzheimers Disease and is often misdiagnosed as Parkinson’s.
—Parkinson (motor) symptoms begin well after cognitive and psychiatric symptoms
—Dementia in 50-80% of PD cases
—PD onset to Dementia is 10 years

Question 23

What are the clinical features of NCD with Lewy Bodies?

Answer 23

Cognitive Decline
—Insidious but progressive
—Complex attention/executive functions affected early
—Visuospatial functions noticeably affected
—Recent memory affected late
—Language largely NOT affected

Visual Hallucinations:
—Complex and organized
—Lower visual fields
—Non distressing
—Recognized as hallucinations
—Med sensitivity:: Levodopa may worsen hallucinations

They have fluctuations in arousal and cognitive functioning

Other clinical features:
—Depression and anxiety
—REM sleep behavior disorder
—Autonomic dysfunction
—Med Sensitivity

Question 24

What are the Parkinsonian symptoms of NCD with Lewy Bodies?

Answer 24

—Shuffling gait/decreased arm swing while walking
—Decreased facial expression (Masked facies)
—Rigidity and stiffness of movement
—Cogwheeling
—Tremor less frequent than PD

**Antipsychotics may worsen Parkinsonian symptoms

Question 25

What are Lewy Bodies and what are the other Neuro characteristics of NCD with Lewy Bodies?

Answer 25

Atypical protein deposits
—Present throughout brain
—Similar to Lewy Bodies found in substantial nigra in PD

Diffuse cerebral atrophy

Motor symptoms due to loss of dopaminergic neurons (PD)
Cognitive sx due to loss of cholinergic neurons (AD)

Question 26

What is Vascular NCD?

Answer 26

Caused by problems in the brains vascular supply. Previously called multi infarct dementia. Emerges over a 5-10 year period.

It’s the 2nd most common form of NCD in the elderly

Question 27

What are risk factors for Vascular NCD?

Answer 27

Hypertension (80%)
Hyperlipidemia
Diabetes
Coronary artery disease
Untreated obstructive sleep apnea
Obesity

Question 28

What does vascular NCD often co occur with?

Answer 28

Alzheimer’s disease

Question 29

What causes Vascular NCD?

Answer 29

—Multiple small CVAs
—Single strategic infarcts
—Diffuse small vessel cerebral vascular disease
—Cerebral Amyloid Angiopathy (accumulations of beta amyloid plaques along walls of cerebral arteries and the breakdown/rupture of vessel walls)

Question 30

What are the Cognitive and Behavioral changes seen in vascular NCD?

Answer 30

Cognitive changes:
—Specific functions affected depend upon locations of CVAs
—Possible lateralized presentation
—Psychomotor slowing/impaired attention/executive dysfunction

Behavioral changes:
—Apathy
—Disinhibition
—Emotional lability/Pseudobulbar affect

Question 31

What is CTE?

Answer 31

A progressive neurodegenerative disease that shares features with Alzheimers and Frontotemporal lobe degeneration (FTLD) and is believed to be caused by repeated brain trauma-mTBI and subconcussive blows.

Ends in a dementia syndrome.

Question 32

What are the symptoms of CTE?

Answer 32

Early Sx:
—Memory and executive dysfunction
—Changes in mood and emotional regulation
—Behavioral changes/impulse control problems

Symptom onset months/years after concussions/blows to the head and worsen progressively

Question 33

What is CTE Incidence and predictors?

Answer 33

Boxing= 17%
Football= 5-25%

Predictors:
—Increased exposure
—Age at retirement
—Duration of career
—Number of bouts
—Poor performance
—Difficult to knockout
—“Brawlers”
—APOE 4 Gene

Question 34

What are the brain anatomical features seen in CTE?

Answer 34

—Ventricular dilation
—Cavum septum pellucidum
—Medial temporal atrophy
—Shrinkage of mammillary bodies
—Pallor of the substantia nigra

Question 35

What Histological features are seen in CTE?

Answer 35

Tau protein positive neurofibrillary tangles in the neocortex
—Predominant in frontal lobe and medial temporal lobe
—Concentrated around penetrating vessels

Neuropil threads in the cortex
—Filaments of abnormally organized phosphorylated tau and ubiquitin proteins

Diffuse amyloid plaques throughout neocortex +/- neuritic plaques

Sparing of the hippocampus