Dementia A brief overview of diagnosis and treatment Amy Sanders MD Assistant Professor of Neurology...
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Transcript of Dementia A brief overview of diagnosis and treatment Amy Sanders MD Assistant Professor of Neurology...
dementia
A brief overview of diagnosis and treatment
Amy Sanders MDAssistant Professor of Neurology
Einstein Aging StudyEinstein-Montefiore Brain Aging Center
Albert Einstein College of Medicine
Coming Up
• Dementia: definitions
• Dementia: evaluation
• Dementia: subtypes
• Alzheimer’s Disease: diagnosis and Rx
• Other Dementia Subtypes: diagnosis and Rx
4.5million
7.7million
2000 2030
Hebert LE, Arch Neurol 2003
13.2million
2050
•What is dementia?
A species of insanity characterized by failureor loss of the mental powers…….
• A syndrome defined by a non-acute decline in cognition that interferes with functioning in everyday living
Multiple cognitive deficits, including MEMORYIMPAIRMENT and at least one of
- aphasia (language impairment)- apraxia (impaired motor activity)- agnosia (impaired recognition)- executive function disturbance (planning)
Disturbance interferes significantly with work or usual social activities/relationships [“ADLs”]
WHAT IS DEMENTIA?
Memoryloss
Problem solvingJudgmentSocial skills
Language
MORE THAN 6 MONTHS
NO NO
Diagnostic Procedures? LABS
?IMAGING
?LP
?EEG
?GENETIC TESTING
Laboratory Tests
• AAN Guideline: B12, thyroid function
• AAN Guideline: maybe syphilis serology
• AAN Guideline:depression screening
• Other labs: CBC, basic chemistry,
LFTs, parathyroid
Imaging
• Structural Neuroimaging: CT, MRI
• Volumetrics: labor-intensive, research
• PET: adjunctive, AD vs FTD
• Amyoid imaging: PIB, research
Klunk, et al. Ann Neurol 2004
Pittsburgh compound B
Active research: biomarkers
EEG: non specific
GENETICS
• Not currently recommended for routine clinical diagnosis
• Complex genetics for late-onset AD
• APOE ε4 allele: susceptibility gene for AD
• Progranulin mutations: FTD
Medication Review
• MANY medications may worsen cognition– Some anti-hypertensives (ß-blockers, CCBs)– Anti-cholinergics– Prednisone– Digitalis– Opiates/narcotic analgesics– Benzodiazepines– Even NSAIDS
DEMENTIA SUBTYPES
ALZEIMER’S DISEASE• Age-related neurodegenerative disease associated
with cognitive decline• Memory, judgment, language• Behavior and mood• Pathology: deposition of amyloid (plaques) and
hyperphosphorylation of tau (NF tangles)• Neuronal cell death and impaired neuronal
function• ? Complex Genetics, vascular risk factors,
Oxidative Stress, inflammation, hormones?
Struldbrugg – race of immortals who “turn to dotage and entirely lose their memories…”
Impaired memory, aphasia, erratic behaviour, paranoia and auditory hallucinations
Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fuer Psychiatrie 1907; 64:146–8.
K. Maurer, S. Volk, H. Gerbaldo. Auguste D and Alzheimer's disease. Lancet 1997; 349: 1546-1549
Why is AD Important?
• Incidence rising—longer lifespans
• Most common neurodegenerative disease
• Most common illness leading to nursing home placement
• $156 billion worldwide cost in 2003
• Treatment available
• Long-term planning (HCP, long-term care)
a new . . . GREAT SUCKING SOUND
Alzheimer’s Disease• NINCDS-ADRDA criteria (probable AD)
• Dementia - established by clinical exam,documented by screening testsconfirmed by neuropsych tests
• Deficits in 2 or more areas of cognition
• Progressive worsening of memory/cognition
• No disturbance of consciousness
• onset 40-90 years, usually > 65y
• Absence of other systemic/brain disorders
• Memory loss that affects job skills. • Difficulty performing familiar tasks. • Misplacing things.
• Problems with language. • Disorientation to time and place.• Poor or decreased judgment. • Problems with abstract thinking. • Changes in mood or behavior. • Changes in personality. • Loss of initiative.
Ten Warning Signs – Alzheimer Association
Memory
Non-memory
Abnormal behaviors & AD
Symptom Months after memory
Calculation defect 25Language 31Irritability 39Gait disorder 47Wandering 50Sleep disorder 51Violence 64Incontinence 67
Folstein & Bylsma,1999
AD: presentation
• Helpful to have informant
• Insidious onset of short-term memory complaint
• Trouble with names, word-finding difficulty
• Getting lost, forgetting parking location
• Trouble calculating – e.g. tips, checkbook
• Planning – recipes, trip planning
AD: behavioral components
• Apathy – loss of initiative
• Depressive symptoms – up to 30%
• Anxiety
• Paranoia, delusions – later stage disease
• Agitation – late disease
AD: Treatment
• Treat the disease: pharm and nonpharm
• Treat the collateral sx – behavior, mood
• Take care of the caregiver-respite
-health lit
AD Pharmacotherapy• Cholinesterase inhibitors
-donepezil (Aricept)
-galantamine (Razadyne [reminyl])
-rivastigmine (Exelon)
• NMDA receptor antagonist– Memantine (Namenda)– Moderate to severe AD, may be additive
Pointers
• Discussion with patient/family: expectations
• Start low and titrate: for all AChI
• Most common side effects: GI (N/V/D)
• Can switch agents
• Withdraw when no longer benefitting or no longer able to interact with family members
Donepezil
• 5 mg qd starting dose (minimum therapeutic dose)
• With or without food, take in a.m.
• Increase to 10 mg after 4-6 weeks
• Half life 70 hours, hepatic metabolism
Galantamine
– Start at 8 mg qd (minimum therapeutic = 16 mg)– Take with food (full meal)– Increase to 16 mg after 4 weeks – 24 mg is maximum dose– Most common side effect: GI– If treatment interrupted for more than 1 week, re-
start at 8 mg and repeat titration– Half-life 7 hours, hepatic metabolism
Rivastigmine
– Start at 1.5 mg BID (minimum therapeutic = 6 mg)– Take with food (full meal) for both doses– Stepwise increase monthly (1.5, 3, 4.5, 6 mg)– 12 mg (6 mg BID) is maximum dose– Most common side effect: GI– If treatment interrupted for more than 1 week, re-start at
1.5 mg BIDand repeat titration– Half-life 90 minutes, renal clearance
Memantine
– Start at 5 mg qd – Take with or without food – Stepwise increase weekly by 5 mg– 20 mg (10 mg BID) is maximum dose– Side effects fewer than with AChI (dizzy, HA)– Half-life 70 hours, partial hepatic clearance
Pharmacologic Treatment of Behavioral Symptoms
• NOT FIRST LINE• Complicated; generally off-label• Rule out other causes• Start low, go slow. Briefest use possible.• Agitation: atypical neuroleptics, anticonvulsants,
benzodiazepines• Depression: SSRIs, S-NE RI, other• Insomnia: trazodone, alprazolam, zolpidem,
ramelteon (may cause carryover sedation)
Vascular Dementia
• 2nd-most common subtype• May be present even in cases
without prominent memory loss• Executive function often
predominates• Vascular risk factors • Gait dysfunction
Diffuse
Lacunes
Multi-infarct
Chui, Arch Neurol, 2000
Variations on the Theme
• “stroke” dementia
• Subcortical pattern: lacunes, severe WMD
• CADISIL
• Often “mixed” with AD
VaD Treatment
• No targeted pharmacologic therapy
• Modification of vascular risk factors
• Aspirin used anecdotally
• Symptomatic treatment of affective symptoms
Dementia with Lewy Bodies
Central Feature: dementia is ESSENTIAL
Core Features:Parkinsonism (spontaneous)Visual hallucinations-recurrent, vivid/detailedFluctuations-attention and alertness especially
Suggestive Features:Severe neuroleptic sensitivity -- worseningREM sleep disorder -- acting out dreamsLow dopamine transporter uptake in BG (SPECT/PET)
McKeith, Neurology, 2005
DLB Treatment
• COMPLICATED– Parkinsonism– Cognition and fluctuations– Hallucinations, psychosis, agitation– REM sleep behavior disorder
“The cold within him froze his old features ... and stiffened his gait.”
“…vivid and detailed hallucinations featuring friends and relatives are common. And like Scrooge’s visions, these phantasms are distressing, often terrifying. Finally, in Lewy body dementia, hallucinations occur early in the disease, frequently before the cognitive deficits are apparent.” Sanders, “Diagnosing with Dickens,”
Sunday NYT Magazine 12/17/06
Frontotemporal dementias
Core• insidious onset, gradual progression• Early decline in social skills• Early decline in regulation of personal conduct• Early emotional blunting• Early loss of insight
SupportiveBehavioral disorderSpeech and language disturbancesPhysical signs – frontal signs, parkinsonism, labile BPInvestigations: neuropsychology, EEG, MRI
Neary, Neurology, 1998
Initial-Carving Doctor Banned
'Dr. Zorro' Blamed Brain Disorder for Scarring Patient
FTD Treatment
• Few options
• AChI not effective, may cause agitation
• Perhaps some role for SSRIs
• Safety assessment
• Depression common in caregivers and can be a reason for earlier nursing home placement