Transcript Memory and cognitive therapy

Memory and treatment of
cognitive impairments
MUDr. Tomáš Kašpárek
Dep. of Psychiatry
Masaryk University, Brno
Contents
Introduction
Physiology and classification
Memory assessment
Disturbances in memory
Treatment of cognitive impairment
Introduction
Definition: ability to register, store, and
recall information (three stages of memory)
Memory: part of cognitive functions
(involved in information processing; such as perception,
thinking, attention)
Dimensions of behavior
– cognition (reasoning) and emotionality
Stages of memory I: Registration
capacity to add new material (sensory,
conceptual, perceptual) to memory
new information need to be properly
processed (percepted) – disturbing factors
– consciousness
– attention
– emotions
– repetition
„Life cycle“ of a memory trace
Immediate memory
– information stored for 15-20s
Short-term memory
– consolidation of the memory trace – several
minutes to 2 days
– medial temporal structures
Long-term memory
– formed trace
– large cortical areas
Stages of memory II: Retention
ability to hold memories in a storage
large # of neurons (changes in connectivity)
involved in the storage of specific memory
– sensory specific fractions of complex
perceptions in corresponding cortical areas
Stages of memory III: Recall
ability to return stored information
active reconstructions
– adding together fractions of the exact
recollection
– in a specific situation (=influence) – possibility
of the failure to represent of past events
properly
– awareness of the recollection, sureness,
proper addressing of time and situation of
recollection acquirement
Types of memory: Memory
modules (Willingham 1997)
Explicit (declarative) memory – medial
temporal cortex
Procedural memory – sensory-motor functional
systems
Working memory – prefrontal cortex
Classical conditioning – cerebellum; relation
between motor function and perception
Emotional conditioning – amygdala; relation
between perception and emotion
Priming - parietal, temporal and frontal cortex
Memory assessment
Immediate recall
– series of numbers (most adult recall 6 # forward and 3
in reverse)
Short-term memory
– names of 3 inrelated objects after 5 min
Long-term memory
– personal history (independent confirmation), general
information (names of presidents...)
Scales – MiniMental State Examination
Specific tests – Wechsler Memory Scale III
Disturbances in memory
General notes
memory = set of functions based on
different neuronal processes = various
dysfunctions according to the pathological
process
Disturbances in registration
pathological process
– disturbed vigilance, attention
head trauma, seizures, delirium, intoxication (BZD,
sedatives), psychosis, depression, anxiety
– disturbed structures involved in memory
consolidation
hippocampus, mammillary bodies, fornix – i.e.
mediotemporal structures
short-term memory dysfunction,
immediate recall may be spared
Disturbances in retention
pathological process
– impairment of large cortical areas
– posttraumatic amnesia
– cognitive disorders
Disturbances in recall
may reflect damaged storage
may occur separately
– failure to recall with later proper recollection
– personality, situation
– attention, fatigue...
„Quantitative“ dysfunctions
Amnesia: short/long-term memory impairment in a state of
normal consciousness
– anterograde: failure to form new information
head trauma, state of CNS dysbalance, drug effect
– retrograde: failure to recall old information
head trauma
dissociative amnesia: patchy or selective
Hypermnesia: unusually vivid memory
– mania, posttraumatic stress disorder (intrusive
memories), obsessive or paranoid personality traits
„Qualitative“ dysfunctions
paramnesias – retrospective falsification of
memories during its recollection (awareness of recalled
memory, failure to proper class time and situation of memory
acquirement)
confabulation – filling memory gaps with
inaccurate information; frontal lobe and self-monitoring?
deja vu – sensation of previously experienced
situation when experiencing the first time
– false awareness of memory
– common in normality, increased in fatigue,
intoxication, complex partial seizures
Treatment of cognitive
impairment
General notes
no specific way to treat memory deficit
treatment modalities focused on the whole
spectrum of impairments in cognitive
disorders
the most data available for Alzheimer's
disease
Psychopharmacotherapy
Reinforcement of cholinergic mechanism
– Cholinesterase inhibitors (ChEIs)
Prevention of excitotoxicity
– Memantine - NMDA antagonists
Cholinesterase inhibitors I
cholinesterases: acetylcholinesterase
(AChE), butyrylcholinexterase (BChe)–
hydrolysis of acetylcholin, thus decrease
its amount in synapses
molecular forms of AChe
– G4 (tetramer) – presynaptic membrane – both
hydrolysis and feedback inhibition; decrease
in AD and aging
– G1 (monomer) – postsynaptic membrane; no
significant decrease
Cholinesterase inhibitors II
donepezil
– long-acting, selective, reversible AChEI
– metabolized by the liver microsome syst.
rivastigmin
– pseudo-irreversible, both AChEI (G1) and BChEI
– no liver microsome metabolism
galantamin
– reversibilie, competitive (increases AC only in areas with low AC
concentration – lower central cholinergic side effects than
noncompetitive inhibitors) AChEI + allosteric modulation
nACR
of
Cholinesterase inhibitors III –
adverse effects
significant cholinergic side effects in 15% of
patients receiving higher doses
most common:
– GIT: nausea, vomiting, diarrhea, anorexia, weight loss
– CNS: headache, dizziness, insomnia, drowsiness,
fatigue, agitation
– CVS: bradycardia, syncope
generally mild in severity, short-lived, related to
titration (slowly!)
caution in patients with asthma, CHOPD, cardiac
conduction defects/clinically significant
bradycardia
Memantine I - Rationale
excessive glutamate release in
Alzheimer's disease (as well as vascular dementia ischemic damage)
excitotoxic degradation of neurons
– progression of cognitive decline, severity of
other symptoms
neuronal degradation is linked with
amyloid accumulation
Memantine II – Mechanism of
action
non-competitive NMDA antagonist
– voltage dependent, fast receptor kinetics – enable
physiologic function (LTP, memory)
decreased activity of glutamate system
hippocampus, neocortex
decreased excitotoxicity - neuronal damage – amyloid
accumulation
i.e. slow down progression of the disease
5HT3 blockade
– facilitation of LTP
– antiemetic effect and regulation of GIT motility
(combination with ACEI)
Memantine III – Clinical efficacy
slower progression of vascular and
Alzheimer dementia
fast onset of action – 2 weeks
improvement of cognitive functions, vigility,
daily activities
reduction of the need for the help of
caregivers
efficacy even in the moderate to severe
disease stages x ACEI
Memantine IV
Adverse events
– generally well tolerated
– higher than placebo: insomnia, dizziness, headache,
hallucinations (NMDA antagonist – PCP)
Pharmacokinetics
–
–
–
–
renal excretion
no extensive metabolization
no cytochrome P 450 inhibition
dosage
20 mg pro die in 2 doses
start: 5 mg, titration: 5 mg per week
References :
Waldinger R.J.: Psychiatry for medical
students, Washington, DC : American
Psychiatric Press, 1997
Kaplan HI, Sadock BJ, Grebb JA.: Kaplan and
Sadock´s synopsis of psychiatry, Baltimore:
Williams and Wilkins, 1997