Alzheimer’s Disease and Other Dementia Related Disorders

Jason Schillerstrom, MDschillerstr@uthscsa.edu

Learning ObjectivesList the diagnostic criteria for Major Neurocognitive

Disorder.

Describe cognitive deficits across multiple domains

Describe the clinical, pathological, and neuropsychological features associated with Neurocognitive Disorder due to Alzheimer’s disease.

Distinguish between Neurocognitive Disorder due to Alzheimer’s disease, cerebrovascular disease, Lewy Body disease, and frontotemporal lobar degeneration.

Major Neurocognitive Disorder1. Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains based on:

◦ Concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function; and

 ◦ A substantial impairment in cognitive performance, preferably

documented by standardized testing or, in its absence, another qualified clinical assessment.

2. The cognitive deficits interfere with independence in everyday activities (i.e. at a minimum, requiring assistance with complex instrumental activities of daily living such as paying bills or managing medications). 3. The cognitive deficits do not occur exclusively in the context of a delirium. 4. The cognitive deficits are not better explained by another mental disorder.

Major Neurocognitive DisorderSpecify whether due to: Alzheimer’s disease frontotemporal lobar degeneration Lewy body disease vascular disease traumatic brain injury substance/medication use HIV infection, prion disease Parkinson’s disease Huntington’s disease another medical condition

Major Neurocognitive DisorderSpecify:1. Without behavioral disturbances2. With behavioral disturbances: if the cognitive disturbance is accompanied by a clinically significant behavioral disturbance such as psychosis, mood disturbance, agitation, or apathy.

Specify:1. Mild: difficulties limited to instrumental activities of daily living2. Moderate: difficulties with basic activities of daily living3. Severe: fully dependent

Key Points #1The diagnosis of neurocognitive

disorders is based on clinical presentation.◦There are no “dementia labs”.◦There is no dementia imaging study.◦Laboratory and imaging are used to

“rule out” reversible causes.

There must be clinically significant functional impairment.

Cognition – Complex AttentionCognitive Domain Definition Examples of Symptoms or

ObservationsComplex Attention Sustained

attention, divided attention, processing speed

Major -Difficulty in environments with multiple stimuli. -Easily distracted. Difficulty holding new information. -All thinking takes longer than usual.

Minor -Requires more double checking than previously. -Thinking is easier when not distracted by radio, TV, etc…

Cognition – Learning and MemoryCognitive Domain Definition Examples of Symptoms or

ObservationsLearning and Memory

Immediate memory, recall memory, remote memory, implicit learning

Major -Repeats self in conversation. -Asks same questions again and again. -Cannot keep track of a short list of item.

Minor -Increasingly relies on lists. -Needs occasional reminders.-Loses track of whether bills have been paid.

Cognition – LanguageCognitive Domain Definition Examples of Symptoms or

ObservationsLanguage Expressive

language, word finding, receptive language

Major -Often uses general terms such as “that thing” and “you know what I mean”. -Prefers pronouns. -Echolalia. -Mutism.

Minor -Noticeable word finding difficulty. -Grammatical errors.

Cognition – Perceptual MotorCognitive Domain Definition Examples of Symptoms or

ObservationsPerceptual Motor Visuoperception,

visuospatial, praxisMajor -Difficulty with

using tools, driving, navigating in familiar environments.

Minor -May need to rely more on others for directions. -May find self lost when not concentrating. -Less precise in parking.

Cognition – Social CognitionCognitive Domain Definition Examples of Symptoms or

ObservationsSocial Cognition Recognition of

emotions, theory of mind

Major -Clearly out of acceptable range.-Insensitivity to social standards in conversation. -Focuses excessively on topic despite others disinterest.

Minor -Less able to read facial expressions. -Decreased empathy. -Increased extraversion or introversion.

Cognition – Executive FunctionCognitive Domain Definition Examples of Symptoms or

ObservationsExecutive Function Planning,

organizing, decision making, overriding habits, mental flexibility

Major -Abandons complex projects. -Needs to focus on one task at a time. -Relies on others to make decisions.

Minor -Difficulty resuming a task after an interruption. -Complains of fatigue from the effort of planning. -Difficulty following conversations of multiple persons.

Key Point #2There are multiple ways to be

cognitively impaired.

Executive function is the cognition that is most strongly associated with self-care abilities and decision making capacity.

Case Example #1: HPI83yr female presents to clinic with her two

daughters.

Daughters are concerned:◦ that their mother repeats her conversations◦ cannot remember the names of her grandchildren◦ became confused and disoriented when shopping

at a local mall.

The patient’s husband died one year ago and daughters are surprised how much they have to help their mother.

Past HistoryNo past psychiatry history.

Only medical issue is hypertension (treated with hydrochlorothiazide)

Retired teacher, 55yr marriage, 2 children

No clinically significant substance use history.

Case #1: Neuropsychological Testing

Age: 83 yearsGDS: 2/15 MIS: 6MMSE: 18CLOX1: 7CLOX2: 7EXIT25: 36

Alzheimer’s Disease Insidious onset and gradual

progression of impairment in one or more cognitive domains.

Subtypes include ‘early onset’ (65 years of age or below) vs. ‘late onset’ (>65 years of age).

Alzheimer’s Association StagingStage 1: No impairment

◦The person does not experience any memory problems.

◦No evidence of symptoms of dementia.

Stage 2: Very mild cognitive decline◦The person may feel as if he or she is having

memory lapses — forgetting familiar words or the location of everyday objects.

◦But no symptoms of dementia can be detected during a medical examination or by friends, family or co-workers.

Alzheimer’s Association StagingStage 3: Mild Cognitive Decline

◦Noticeable problems coming up with the right word or name.

◦Trouble remembering names of new people.◦Having noticeably greater difficulty

performing tasks in social or work settings.◦Forgetting material that one has just read.◦Losing or misplacing a valuable object.◦ Increasing trouble with planning or

organizing.

Alzheimer’ Association StagingStage 4: Moderate Cognitive

Decline◦Forgetfulness of recent events.◦Greater difficulty performing complex

tasks, such as planning dinner for guests, paying bills or managing finances.

◦Forgetfulness about one's own personal history (usually medical).

◦Becoming moody or withdrawn, especially in socially or mentally challenging situations.

Alzheimer’s Association StagingStage 5: Moderately severe cognitive

decline◦Unable to recall their own address or

telephone number or the high school or college from which they graduated.

◦Become confused about where they are or what day it is.

◦Need help choosing proper clothing for the season or the occasion.

◦Still remember significant details about themselves and their family.

◦Still require no assistance with eating or using the toilet.

Alzheimer’s Association StagingStage 6: Severe cognitive decline

◦Lose awareness of recent experiences and surroundings.

◦Difficulty remembering the name of a spouse or caregiver.

◦Need help dressing properly and may, without supervision, make mistakes such as putting pajamas over daytime clothes or shoes on the wrong feet.

◦Need help handling details of toileting.◦Experience major personality and behavioral

changes, including suspiciousness and delusions.

Alzheimer’s Association StagingStage 7: Very severe cognitive

impairment◦Lose the ability to respond to their

environment and to carry on a conversation. ◦Need help with much of their daily personal

care, including eating or using the toilet. ◦They may also lose the ability to smile, to

sit without support and to hold their heads up.

◦Reflexes become abnormal. ◦Muscles grow rigid. ◦Swallowing impaired.

Well Elderly

AD Affects Both ECF and Constructions

AD Pathology

http://www.umsl.edu/~homecare/brain1.PDD.jpg

AD Pathology

Tangle

Plaque

FDA Approved MedicationsAcetylcholinesterase Inhibitors

◦donepezil (Aricept)◦rivastigmine (Exelon)◦galantamine (Razadyne)◦tacrine (Cognex)

memantine (Namenda) – NMDA antagonist

Summary of FDA Approved Medications

All have demonstrated efficacy by the chosen outcome measures.

However, the effect size is small.

Few patients actually show improvement.

Some outcome measures are less relevant.

Exercise.

Case Example #2: HPI 73yr man presents to clinic with his wife.

She expresses concern for her husband stating, “I think he’s depressed. He just sits in his chair all day doing nothing. I have to do everything.”

He no longer manages finances and he needs assistance with his medications.

He denies feeling depressed and doesn’t understand wife’s concerns.

Past HistoryTakes medication for diabetes,

hypertension, and elevated cholesterol.

Had heart catheterization for coronary artery disease 5 years ago.

Retired produce salesman, married to current wife 22 years, 3 adult children.

Smokes one pack per day. Drinks 6-12 beers per week.

Case #2: Neuropsychological Testing

Age: 73 years

GDS: 2/15 MIS: 8MMSE: 26CLOX1: 4CLOX2: 9EXIT25: 30

Vascular DementiaEvidence for decline is prominent in

complex attention and frontal-executive function.

Memory is less impaired relative to loss of executive function.

Focal neurological signs

Evidence of hypertension, valvular heart disease, vascular disease, atrial fibrillation.

Vascular Dementia Affects the Executive Control of Clock-drawing

Vascular Dementia

Vascular Dementia

TreatmentMust prevent future stroke /

vascular disease:◦Aspirin◦Anticoagulants◦Exercise

Off label treatments for apathy◦Antidepressants (sertraline)◦Stimulants (methylphenidate)

Case #3: HPI 93yr female is brought to clinic by her daughter

(patient lives with daughter).

Daughter reports significant cognitive and functional decline over the past 1-2 years.

The patient reports occasionally seeing little men walking across her mantle.

She was started on antipsychotic by PCP and had severe dystonic reaction.

Daughter also reports that the patient talks and moves excessively in her sleep.

Past HistoryTakes medications for heartburn,

urinary incontinence, constipation, hypertension, and atrial fibrillation.

Reports frequent falls (3 in last year).

12th grade education, housewife, widowed 12 years.

No substance use history.

Case #3: Neuropsychological Testing

Age: 93 years

GDS: 1/15MIS: 6MMSE: 22CLOX1: 5CLOX2: 7EXIT25: 24

Lewy Body DementiaCore Features:

◦Fluctuating cognition with pronounced variations in attention or alertness.

◦Recurrent visual hallucinations that are well formed and detailed.

◦Spontaneous features of parkinsonism, with onset subsequent to the development of cognitive decline.

Lewy Body DementiaSuggestive Features

◦Meets criteria for rapid eye movement (REM) sleep behavior disorder.

◦Severe neuroleptic (antipsychotic medication) sensitivity.

ParkinsonismCognitive deficits are more

closely associated with rigidity and bradykinesia as opposed to tremor.

Parkinsonism in DLB tends to be:◦Less severe than that observed in PD◦More symmetric compared to PD◦Associated with more gait

abnormalities◦Less responsive to levodopa

(Sinemet)

Visual HallucinationsFully formed, detailed, 3-

dimensional objects, people or animals

Occur in 59%-85% of autopsy confirmed Lewy Body Dementia

Occur in early in the course of the disease (relative to AD hallucinations)

FluctuationsMimics delirium: waxing and waning of cognition,

behaviors, and arousal.

10% - 80% with poor inter-rater reliability

Differentiating DLB from AD:◦ Daytime drowsiness◦ Daytime sleep of 2 hours or more◦ Staring into space for long periods◦ Times when the patient’s ideas are disorganized, unclear

or illogical

3 out 4 has a positive predictive value of 83%

Other FeaturesREM Sleep Behavior Disorder:

augmented muscle activity and dream content; typically precedes onset of dementia, hallucinations, and Parkinsonism

Autonomic Instability

Perhaps a greater rate of decline

More responsive to acetylcholinesterase inhibitors.

Lewy Bodies

Kondi Wong, Armed Forces Institute of Pathology

Case Example #4: HPI APS called to investigate 60yr woman with self-neglect.

Squalor dwelling. No electricity, water, or sewer.

The client had a $2000 past due water bill and a ~$350 past due electrical bill.

APS facilitated a voluntary placement in a supervised setting where the client was allowed to take her dog. However, she became upset with management and decided to leave. 

Would like to renovate home. Plan is to have Channel 4 News do a fundraising story for her.

Case Example #4 #1

Case #4: Neuropsychological Testing

Age: 60 years

GDS: 1/15 MIS: 8MMSE: 30CLOX1: 6CLOX2: 13EXIT25: 26

Frontotemporal Dementia – Behavioral Variant

1. Three or more of the following behavioral symptoms:a. Behavioral disinhibitionb. Apathy or inertiac. Loss of sympathy or empathyd. Perseverative, stereotyped or compulsive

behaviore. Hyperorality and dietary changes

2. Prominent decline in social cognition and/or executive abilities

3. Relative sparing of learning and memory and perceptual-motor function.

Frontotemporal Dementia – Language VariantProminent decline in language

ability in the form of speech production, word finding, object naming, grammar, or word comprehension.

Relative sparing of learning and memory and perceptual-motor function.

Frontotemporal DementiaFrontal and anterior temporal atrophy

(typically clearly detectable on CT or MRI scans), rarely parietal atrophy

Frontotemporal hypometabolism

Pick bodies (silver staining/argentophilic) intranuclear inclusions

Neuritic plaques/tangles not present

Frontotemporal Dementia

Frontotemporal Dementia

Frontotemporal Dementia

Off-Label Therapies for AgitationAntidepressants

Benzodiazepines

Antipsychotics◦Black box warning◦Increased risk of falls, stroke, and

death