Since 1960 Medicine Korat โรงพยาบาลมหาราชนครราชส มา Dementia and Alzheimer s disease Concise Reviews PAWUT MEKAWICHAI MD DEPARTMENT of MEDICINE MAHARAT NAKHON RATCHASIMA HOSPITAL 1
Prevalence Increase with Age Age % 60-64 1 65-69 2 70-74 4 75-79 8 80-84 16 85+ 32
Memory System MINOR MEMORY CIRCUIT: cortex MAIN MEMORY CIRCUIT: limbic system
Minor Memory Circuit: cortex Parietal lobe dominant: language, complex motor function non-dominant: visuospatial (dressing, copy, direction) Temporal lobe lateral: auditory function medial: memory Occipital lobe visual function
Minor Memory Circuit: Frontal cortex Frontal lobe : dorsolateral: cognitive function, judgement, planning, shift task, attention orbitofrontal: social inhibition = disinhibition syndrome medialfrontal: social interaction = apathy
Frontal lobe Syndrome slow in both physical and mental impaired executive function disinhibition, confabulation impair working memory, poor attention poor recall (both cue and not-cue) with good recognition Three step command: Luria (fist-edge-palm) Executive function: trail A and B - stroop (say COLOR not the word) - verbal fluency: category and letter difference between category and letter favor temporal or frontal - clock drawing test
Main Memory Circuit: limbic system group of nuclei below neocortex mesocortex & archeocortex control emotional, homeostasis and basic need olfactory bulb neocortex corpus callosum fornix dentate gyri amygdala mesocortex thalamus
At least 6 months of DSM IV-R Criteria for Dementia A. Impair short and long term memory B. At least one from the following 1. aphasia 2. agnosia 3. apraxia 4. disturbance of executive function (planning, judgement, organizing, abstract thinking) C. In A and B disturb function, social and relation D. No delirium E. No organic cause or mental disorder
Test for Detected Dementia - Thai mini-mental state examination (TMSE) - MOCA test - Clock drawing test - Alzheimer s disease assessment scale-cognition (ADAS-Cog) - Clinical Dementia Rating (CDR) - Global Deterioration Scale (GDS) - Dementia Severity Rating Scale (GSRS)
normal ageing change mild cognitive impairment : MCI delirium depression: pseudodementia reversible dementia Differential Diagnosis
Normal Ageing Change/ Age Associated Memory Impairment (AAMI) self recognized normal cognitive test no impact, normal function stable Memory: preserve long term but recall reduce Attention: reduce attention and impair shift task Language: preserve verbal but difficult retrieval Reasoning: slow and reduce covering new problem Processing: reduce speed both cognition and motor (poor learning new issues)
Mild Cognitive Impairment : MCI definition? (incidence 5-25%) mild cognitive impairment can recognized by self or family impair mental status test (not reach to dementia) normal or near normalactivity daily living may impair executive function
MCI classifications
MCI prognosis Prognosis Stable=MCI Recovery=normal Progress=AD functional impairment Small volume of entorrhinal cortex and hippocampus metabolism tempero-parietal region
Normal to AD 1-2% per year MCI to AD 12% per year MCI conversion to AD RISK Advance age Behavior symptoms esp. depression Impair IADL Slow gait: motoric cognitive risk syndrome Olfactory dysfunction CV risk ApoE4 + high turning rate in early phase and reducing by time MCI Conversion risk
MCI Conversion to AD
Delirium acute decline in attention and cognition typically daytime drowsiness, nighttime insomnia or fragmented sleep disorientation, memory deficits language impairment, illusions or hallucinations vulnerable patient and exposure to precipitating factors (medical condition (multifactor)) persons who are 65 years or older
Depression: pseudodementia not uncommon in elderly (7-10%) SIG E-CAPS Sleep, Interest, Guilt, Energy, Concentration, Appetite, Psychomotor agitation and/or retardation Suicidal idea
Reversible Dementia Irreversible cause - Alzheimer's disease - Vascular dementia - Diffuse Lewy body dementia - Frontotemporal dementia Reversible cause - metabolic: hypothyroid, B12 def., alcoholism, CRF - infection: SY, CJD, HIV (ADC) - mass lesion: tumor, CSDH - normal pressure hydrocephalus (dementia, ataxia, urinary incontinence) - others: SLE, Huntington, Wilson s disease - depression (pseudodementia)
Approach in Dementia Dementia? (DSM IV-R) investigation for r/o reversible cause CBC, VDRL, TFT, BUN, Cr, brain image reversible irreversible Alzheimer's disease Vascular dementia Diffuse Lewy body dementia Frontotemporal dementia
Alzheimer s Disease Pathology: Macroscopic cerebral cortical atrophy (not relate to degree of impairment) mark atrophy at frontotemporal, hippocampus and spare primary motor, sensory and visual area symmetrical dilatation of ventricle
Alzheimer s Disease
MRI in Alzheimer s disease temporal / hippocampal atropy
Alzheimer s Disease Pathology: Microscopic Neurofibrillary tangles (intracellular) - pyramidral shaped - Tau protein component - Double helical configuration (EM) - Disrupt intracellular transport Amyloid (senile) plaque (extracellular) - inflammatory process - degenerative neurite
Risk Factors Age Female : Male = 1.2:1 Low education: learning process is increase neuronal synapse Hereditary disease
Cognitive function Clinical Progression of AD Time? 0 y Time (y) 10 y MCI MMSE 25 30 Mild AD MMSE 18 24 Mild subjective/ objective memory loss Normal function Forgetfulness Repetitive questions Daily function mildly impaired Progression of cognitive deficits Word-finding difficulties Supervision required Moderate AD MMSE 10 17 Severe AD MMSE 0 9 Agitation Altered sleep patterns Total dependence: dressing, feeding, bathing
Severity Progression AD: Mini-Mental State Examination (MMSE) MMSE Score Stage Level of autonomy 25-30 Normal Independent living 18-24 Mild AD Independent living 10-17 Moderate AD Supervision required <10 Severe AD Total dependence
AD Caregiver Time by Disease Severity
Patient Evaluation: ABC A: Activity of daily living : instrument and basic B: behavioral and psychological of dementia C: Cognition and care giver
Treatment of AD ChE-I NMDA agonist Others rivastigmine doneprezil galantamine memantine gingko estrogen selegiline vitamin E statins NSAIDs
Efficacy of ChE-I delay cognitive decline delay functional decline improve behaviors ChE-I improve ADL
Pharmacokinetics slow titration for avoiding adverse effect GI side effect is the most common domperidone may be useful improve after first 3 months naturally decline but still beneficial over the placebo no double or triple therapy awareness with anticholinergic medication eg. TCA NNT 7, NNH 12
Conclusion Dementia is a clinical syndrome Treatable cause must be identify TMSE is the most useful screening test A (ADL) B (behavior) C (cognitive, care giver) are the key of follow up Early detection of dementia can improve QOL Of patient and caregiver 34
Conclusion ChEI and NMDA agonist are only the medication for slow progression of AD High dose = High benefit but GI side effect limit the efficacy 35