Cognitive Neurology, Dementia and Alzheimer's Disease

What part of the brain is used to remember things associated with strong emotion?

Amygdala

What part of the brain is used to remember things related to movement (muscle memory)?

Cerebellum

Describe the hippocampus

Part of the brain that is involved with short term memory and facts. They are tucked underneath the temporal lobes, so they can be easily crushed in trauma.

What part of the hippocampus is attacked in Alzheimer's disease?

CA1 region.

What is the entorhinal cortex?

Bridge between the temporal lobe and hippocampus. Involved in the early stages of Alzheimer's.

What are the 2 major types of memory?

Declarative (facts and events) and nondeclarative (skills, habits, classical conditioning)

What are the domains assessed in a standardized cognitive assessment?

1. Language

2. Executive function

3. Abstract reasoning

4. Memory

5. Attention/concentration

6. Visuospatial skills

What is the Mini-Cog test?

Ask the patient to remember 3 words, and repeat them back immediately.

Have the patient draw a clock face

Ask the patient to repeat the 3 words.

What does the MMSE evaluate?

Orientation

Registration

Attention and calculation

Delayed recall

Language

Visual construction

Better for later findings, not early disease

What does the MOCA evaluate?

More sensitive to subtle cognitive changes

Visuospatial/executive

Naming

Memory

Attention

Language

Abstraction

Delayed recall

Orientation

What qualifies mild cognitive impairment?

Decline in cognitive domains that are abnormal for age and level of education. Difficulty with ADLs but still independent.

What are the criteria for mild cognitive impairment?

Preserved daily functioning

Impairment in 1 or more cognitive domains

Self or informant reported cognitive decline

Does NOT meet criteria for dementia

How is MCI diagnosed?

Standardized cognitive assessment. Referral for in-depth neurocognitive assessment if needed.

Can also do brain scan.

What is the treatment of MCI?

Treat reversible causes, if identified.

Exercise and diet improvement.

Cognitive training.

Stop smoking!

What is the prognosis of MCI?

7x more likely to develop AD over time.

Patients with more severe memory impairment are more likely to progress.

Early data suggests that lateral spread of tau may predict a poor prognosis and more rapid progression.

What are some treatable causes of dementia?

Drugs

Depression

Metabolic issues

NPH

Infections

Anemia

What is dementia?

Acquired deterioration in memory and other cognitive skills that reduces a person's ability to perform everyday activities. Persistent and progressive over time.

What are risk factors for dementia?

Advanced age

Family history

Co-morbid conditions like DM, HTN, hyperlipidemia.

Unhealthy lifestyle

How do you evaluate and diagnose dementia?

Standardized cognitive assessment

Labs like CBC, UA, CMP, Vitamin B12, folic acid, thyroid to rule out other causes

MRI of brain

What is the diagnostic criteria of dementia?

Acquired loss of cognitive abilities with impairment of at least 2 of the following:

Memory

Language

Executive function

Visuospatial abilities

Gnosis (ability of the brain to recognize previously learned information)

Praxis

Social/emotional abilities

What is the treatment of dementia?

No cure but the goal is to delay progression and maintain remaining capabilities.

Symptomatic management and plan for the future.

If you are going to use meds for AD, MAKE SURE your patient actually has AD and not another type of dementia. YOU WILL MAKE THINGS WORSE!

What is neurodegenerative disease?

Progressive loss of neurons that leads to: impairment of intellectual function, memory and/or language, and alterations in behavior.

What are types of neurodegenerative disease?

Alzheimer's (most common type)

Frontotemporal dementia

Lewy-body and Parkinson's dementia

Huntington's disease

What is Alzheimer's disease?

The most common cause of dementia (2/3 of cases). It is irreversible and progressive. Affects language, memory, comprehension, attention, judgement and reasoning.

What are the risk factors for AD?

> 65 years of age

Family history (though 95% is sporadic)

DM

HTN

What are the genetics of AD?

Autosomal dominant pattern. Most times genes aren't screened but if there is a strong family history they will.

APOE gene increases risk (14x more likely)

What is the most prominent theory of AD pathophysiology?

Amyloid hypothesis. There is a build up of amyloid plaque in the brains of patients' with AD. Deposits of this protein are found in clumps in brain tissue, and this is the pathologic diagnosis of AD.

What is another common hypothesis of AD pathophysiology?

Tau hypothesis. Microtubules in the brain get broken down and release tau, which accumulates in the neuron and forms neurofibrillary tangles (NFTs)

What is hydrocephalus ex vacuo?

In severe AD, the ventricles of the brain appear larger because so much brain tissue has gone away. The pressure in the brain isn't increased, so this isn't true hydrocephalus.

Which other genetic condition increases the likelihood of someone developing AD?

Down syndrome (Trisomy 21)

What are the symptoms of AD?

Anterograde amnesia

Declarative episodic memory loss (conversations, events, intentions)

Loss of visual spatial abilities

Loss of language, speech

Overall symptoms vary on stage.

How is AD diagnosed?

Definitive diagnosis can only be made by postmortem exam of brain (many families do not choose to do this)

Clinical history, standardized cognitive evaluations, labs, neuro imaging all helpful with diagnosis. Make sure to get brain MRI!

What are the medications for AD?

Cholinesterase inhibitors like Donepezil (Aricept), Galantamine (Reminyl) and Rivastigmine (Exelon).

Also N-methyl-D-aspartate receptor antagonist like Memantine (Namenda)

What medication is used for mild to moderate AD?

Cholinesterase inhibitors like Donepezil. Titrate slowly up to 10mg/day

What medication is used for moderate to severe AD?

Memantine. Titrate slowly up to 20mg/day.

What is the average life expectancy of someone with AD?

4-8 years. Some may live up to 20 years after diagnosis.

Most common cause of death is pneumonia.