• Delirium (acute confusional state, with altered consciousness)
• Dementia of depression (pseudodementia)
• Focal neurological symptoms (ie due to stroke or psychological conditions) 
  • aphasia
  • amnesia

• Determined by comparison with previously known baseline of cognitive function
• Acquired and slowly  progressive impairment of Memory (1st) then other cognitive fxns (language, visuospatial skills, calculations)

1. Impairment of Memory
2. Impairment in at least 1 other area of cognition: aphasia, apraxia, agnosia, executive function
3. Significant declines in social occupational function from previously baseline
4. Should not occur in setting of altered consciousness (this would be delirium)

Early symptoms: memory and learning impairment

Later: word-finding and naming problems

1. MCI (mild cognitive impairment)
2. Vascular Dementia
3. Dementia with Lewy Bodies
4. Frontotemporal dementia

- early changes in memory and thinking that may be prodromal to dementia (pts with this dx progress to AD at    a rate of 10-12% per year, however not all pts progress)

- Memory complaint by pt

- No problems in ADLs

- Abnormal memory for age but normal cognitive function (No Dementia)

- Does not imply continued progression, NOT a predictor of dementia 

- Those with initial dx of MCI, no cognitive impairment at follow up 1-5 years later

• "benign senescent forgetfulness"
• "age associated memory impairment" 
• "Late-life forgetfulness"
• Implied that some memory change with age is normal: NOT TRUE

• Most common type of dementia
• Neurodegenerative disorder
• complex mix of genetic and environmental factors
• Clinical dx based on established criteria
• labs and medical eval including brain imaging rules out other causes of dementia (ie Parkinson's, Multiple lacunar infarcts)

• Insidious onset
• Followed by decline in multiple cognitive abilities over years
• 1st sx: inability to learn new material (rapid forgetting or loss of short term memory)
• additional cognitive problems follow

• before age 60
• familial AD (genetic component)

• more common form
• no obvious inheritance pattern in most families

• Get good family hx
• make sure to get history from multiple informants for accuracy
• look for family hx of AD in a 1st degree relative (parent of sibling): risk factor for AD

• Premorbid cognitive, social, occupational functioning
• Substance abuse Hx, including prescription
• Med hx and ROS: Id risk factors for various dementia syndromes, clues to DDx 
  • ALL meds taken over past 6 months (including OTC, and herbals)

• Chronological account of sxs of cognitive and functional decline (from family)
• Onset, course and features of dementia syndrome
• Start hx when cognitive changes 1st noted
• Focus on evolution of cognitive, nerupsych and relevant motor and functional symptoms

• Early sxs are under recognized 
• Onset insidious as dz progresses slowly
• progression varies from person to person
• Each of 3 stages lasts an average of 3 years

• Memory impairment
• Personality and affective (mood) changes
• Problems with instrumental ADLs (ie balancing check book)
• ADL difficulties absent or minimal 
• Neuro findings and motor skills unaffected

• Impairments in language (aphasia), learned motor skills (apraxia), forget things previously known how to do
• ↓ recognition of people, places and situations (agnosia)
  
• supervision with IADLs
• Impaired fine motor coordination
• may need help with ADLs

• Severe memory impairment
• Help needed with ADLs
• Hyperreflexia, gait apraxia, frontal release signs (primitive grasp and snout reflexes)
• Parkinsonian symptoms
• Possible myoclonus
• Impaired function
• Marked rigidity, diffuse hyperreflexia (4+), spasticity, progressive inability to swallow

• Usually begin to occur in stage 2
  • Delusions (fixed false beliefs): 30-40% of pts 
  • Hallucinations (often visual: esp in pts with glaucoma or macular degen; also auditory): 10-25%
  • Sleep disturbances
  • Overactivity/aggression/agitation
  • Depression 

• 2nd most common type of dementia
• Cause: cerebrovascular abnormality
  • Usually ischemic: ischemic vascular dementia
  • might be a single stroke causes dementia
  • might be multiple small strokes causing multiple-infarct dementia: discrete events and stepwise decline
  • Chronic ischemia also a cause

• Presence of dementia
• documentation of a single stroke temporally related to onset of dementia or...
• Evidence of at least 2 ischemic events based on hx, neuro signs and/or brain imaging
• Evidence of at least 1 infarct outside the cerebellum on brain imaging
• Dx supported by a hx of multiple ischemic attacks and vascular risk factors

• 3rd most common type of degenerative dementia (much more rare than 1st 2 types of dementia)
• Dx based on clinical criteria
• dementia must be present
• a memory problem may not be prominent early in dz
  • it does become evident on dz progression
• Early problems with: attention, executive and visuospatial skills
• Need 2 of 3 additional features to Dx: 
  • Fluctuating cognition with extreme variations in attention and alertness (great & bad days)
  • Recurrent, fixed visual hallucinations
  • Spontaneous motor features of parkinsonism: rigidity, bradykinesia, postural instability, tremor

• Chronic Dementia of insidious onset
• earliest sxs usually behavioral 
• decline in and problems regulating social interpersonal conduct
• Emotional blunting and early loss of insight
• Sometimes problems with expressive aphasia (word retrieval)
• Early semantic dementia (loss of ability to name and understand words and to recognize stimuli)
• Decline in memory late in dz
• Parkinsonian features may develop

• overlap can occur among degenerative forms of dementia
• Ex: pt with definite stroke may develop insidious onset of cognitive decline several years later (AD)
• Others, with clear cut AD may have an ischemic stroke

• AD: Brains of pts with dementia contain both amyloid plaques and neruofibrillar tangles in sufficient # 
• Vascular dementia: ischemic vascular changes (stroke, lacunae or microvascular dz) showing sig cerebrovascular dz

Frontal lobe dz.

(differentiation from dementia)

• Frontal lobe dz: preserves memory and cognitive fxns
• Deficits in
  • Verbal fluency ("name as many vegetables as you can")
  • sequential hand movements
  • Executive fxns: goal directed and motivated behavior and decision making

• CBC
• Sed Rate
• Electrolytes
• Blood chemistries
• Vit B12 and folate
• Thyroid function tests
• VDRL for syphillis

Distinguishes depression from AD

• Depression: attention/concentration most impaired
• A depressed person learns 3 words with repeated effort
• A pt with moderate-severe AD does not learn

maybe

use clinical judgment

• Most dementias: >65 yo
• 65-69: 0.2% prevalence (doubles every 5 years)
• 85 yo: 18% prevalence rate
• AD: around 77% of all Dementias
  • 26% DLB (Lewy bodies) can be present in different types of dementia
  • 18% Vascular (VaD)
  • 5% frontotemporal (FTD)

• Most severely effects temporal and parietal lobes
• Causes neurofibrillary tangles and amyloid plaques
• Cholinergic neurons most effected
• There is inherited susceptibility
• Gees for B-amyloid precursor protein and apolipoprotein E

• present in 20-40% of AD pts; always look for
• Several types exist: reactive sadness to major depressive disorder
• Not generally present with severe AD
• Less likely as AD progresses
• Severe AD <10% major depression
• Quality of life improves with antidepressant therapy
• 10-15% have less severe depression

Presence of any one or more sxs:

• Frequent crying
• Frequent references to death, suicide, futility 
• continuous failure to experience pleasure and enjoyment

• Irritability
• complaining
• demandingness
• Dependency
• Clinging
• May all be improved with antidepressant use

• Any of the SSRIs are good choices, except paroxetine (Paxil)
• Start low, go slow
• TCAs have significant anticholinergic effects
  • No real value with AD patients
  • Contraindicated with AD

• ↑ emotional stability
• shorten dysphoric mood states
• calm the pt
• ↓ distractibility
• classic frontal lobe symptoms do not respond to antidepressant therapy

• In 50% of pts with AD
• associated with more severe dementia
• Hallucinations are common
• False beliefs may not represent psychosis if and explanation lowers their concern
• If they cling to false beliefs and use aggression and hostility to defend them: Psychotic

• Low dose haloperidol (Haldol) is tmt of choice
  • 1-2 mg either at bedtime or in divided doses
• OR...
• Thioridazine (Mellaril) 12.5-50mg qd may help
  • 100-200 mg qd max dose in AD
  • Has sedating properties
• Atypicals: ie Risperidone (Risperdal) 0.25-0.5 mg bid helps. As dose ↑, greater hypotension and headache
  

• Generalized behavioral perturbation + arousal + 1 or more of the following symptoms:
  • motor restlessness
  • Pacing
  • repetitious vocalizations &/or acts
  • Self-abusiveness &/or aggressiveness towards others
  • irritability with minor stimulation
  • belligerence 
  • fearfulness
  • sleeplessness (often day/night reversal)
  • Anger, hositlity

• Agitation not due to a superimposed delirium, acute or chronic medical illness (CHF) or New neuro illness (stroke)
• CNS side effects from medications have been ruled out

• If pt has associated medical condition (UTI or Pneumonia) optimizing tmt for that condition usually ↓ agitation
• ↓ environmental stimulation
• reverse any environmental changes

• Cognitive decrease
• Pain, fever
• CNS medication side effects
• any sensory loss
•  any environmental changes

• Trazodone (Desyrel): sedation, calming effect
• Busprione (Buspar): not good choice, if pt is psychotic try ↑ Haldol 1st
• Lorazepam (ativan): for acute agitation 
• Mellaril 12.5-50 mg may help 
• Zolpidem (ambien)
• Risperidione (Risperdal)
• Anticonvulsants: Carbamazepine (Tegretol) or Divalprox sodium (Depakote): mood stabalizers

• Begin 2-50 mg at bedtime
• ↑ dose gradually to 150 mg or greater
• Possible side effects: postural hypotension
• may use in divided doses during daytime

• Lorazepam (ativan) 0.25-2.5 mg 
• Acute agitation only
• impair memory, use only until other agents become effective

• Non-benzodiazepine hypnotic 
• start 2.-5 mg at bedtime and 1.25-5 mg PRN during day
• good for late-stage AD

• Anticonvulsants
• mood stabilizing effects
• Carbamazepine (Tegretol)
• Divalproex Sodium (Depakote)

• Counseling for some demented pts who retain some memory and limited interaction skill
• Give small index cards with key concepts on it from counseling
• ex: for unreasonable demands "I CAN'T DO THAT", "I AM SCARED"
• this manages caregiver's behavior toward pt

• All forms of AD involve chronic degeneration of brain neurons, especially those that release acetylcholine
• Cholinergic neurons destruction causes cholinergic deficit
• AD pts brains contain senile plaques and neurofibrillary tangles concentrated in same regions as cholinergic deficit
• Cholinergic decline linked to neruopsychiatric and functional deficits in AD

1. use cholinesterase inhibitor in appropriate pts
2. don't respond, use antipsychotics

• Used for moderate to severe AD
• Memantine 5mg qd
• Targets the glutamatergic system
• shows clinical benefit and good tolerance

Randomized, placebo controlled study showed that adding memantine with aricept for 24 weeks: sig better outcomes compared with placebo on

- cognition

- ADL

- Behavior

- clinical global status

• All except tacrine showed similar efficacy
• sig improvements seen vs pts on placebo
• equivalent to delaying dz by 6 months to 1 year: better at preventing decline than improving performance
• Temporarily delay cognitive decline
• delay declines in functional ability
• improve troublesome behavioral symptoms
• Avoid polypharmacy
• use lowest effective dose for least necessary duration
• seek symptom reduction rather than elimination
• when aggression is present, antipsychotic is better than anxiolytic (ie ativan)

• Vitamin E has demonstrated efficacy
• Esp along with donepezil
• Anti-inflammatory agents: showed negative outcomes
• Herbal remedies: no studies
• In trials: 
  • Statins
  • passive immunization with human monoclonal Ab vaccine that binds to and clears beta amyloid peptide