Dementia Arden L Aylor, MD Geriatrics Texas Tech University

Goals & Objectives  Statistics  Clinical Features  Diagnostic Criteria  Assessment Methods  Treatment Methods

Normal vs. Abnormal Aging  >40 year-old: Age Associated Memory Impairment  Decline in Hepatic & Renal function  Vision changes  Hearing changes

Dementia  Definition: The loss of cognitive and intellectual function, without impairment of perception or consciousness  Characterized by disorientation, impaired memory, judgment, intellect and labile affect

Did you Know…  Five major types of Dementia Alzheimer’s: 60-70% Alzheimer’s: 60-70% Cerebrovascular: 15-25% Cerebrovascular: 15-25% Lewybody: 5-8% Lewybody: 5-8% Frontotemporal: 3-5% Frontotemporal: 3-5% Parkinson's with Dementia: 1-3% Parkinson's with Dementia: 1-3%  Estimated by 2040, 120 million Arch Neuro, 2005 Arch Neuro, 2005

Did you Know…  Prevalence: 6-8% 60 yrs and doubles every 5 years  80 yrs: 47-50% population suffer from some form of dementia

Did you Know…  total cost world wide exceeded $220 billion acute care acute care long-term care long-term care home health care home health care lost productivity for caregivers lost productivity for caregivers

Genetics  The two major risk factors for dementia age age family history family history  Alzheimer’s: 50% penetrance in first degree relatives by age 80

Genetics  Alzheimer’s (AD): before age 60 genetic mutations on chromosomes 1, 14, 21 genetic mutations on chromosomes 1, 14, 21  Alzheimer’s (AD): after age 60 apolipoprotein E gene (APOE) on chromosome 19 apolipoprotein E gene (APOE) on chromosome 19

Genetics  APOE* 4/4 allele 6x increase risk in (AD)  APOE* 2 appears to be protective  Other risk factors: head injury, education level, estrogen replacement after menopause, long-term NSAID’s head injury, education level, estrogen replacement after menopause, long-term NSAID’s

Clinical Features  Memory Impairment  Early Dementia: difficulty learning and retaining new information difficulty learning and retaining new information  Late Dementia: inability to access distant memories, impaired judgment and executive function inability to access distant memories, impaired judgment and executive function

Clinical Features  Dementia has a profound effect on the patient’s daily life: ADL’S (eating, bathing, grooming) ADL’S (eating, bathing, grooming) planning meals planning meals managing finances managing finances medications medications communication communication driving driving

Clinical Features  Early behavior and mood changes are common: personality alterations personality alterations irritability irritability anxiety anxiety depression depression  Late findings: Delusions, hallucinations, aggression and wandering

Clinical Features  Dementia and depression often overlap  Depressed patients usually exhibit intact language and motor skills  55% over 65 yrs with mild cognitive impairment + depression, progress to moderate to severe dementia within 5 yrs Arch Neuro, 2005

Clinical Features  Dementia & Agitation undiagnosed medical problem undiagnosed medical problem pain pain depression/ anxiety depression/ anxiety delirium delirium environmental changes environmental changes

Six Diagnostic Criteria for Dementia  1.Multiple cognitive deficits a. Memory impairment a. Memory impairment b. One or more of the following: b. One or more of the following: aphasiaaphasia apraxiaapraxia agnosiaagnosia disturbance in executive functiondisturbance in executive function Core Geri, 2005

Six Diagnostic Criteria for Dementia Six Diagnostic Criteria for Dementia  2. Cognitive deficits in 1a and 1b causing an impairment in social or occupational function which represents a significant decline from a previous level  3. Course is characterized by gradual onset and continued cognitive decline

Six Diagnostic Criteria for Dementia  4.Cognitive deficits in 1a and 1b are not due to any of the following: central nervous system condition causing progressive deficits in memory or cognitioncentral nervous system condition causing progressive deficits in memory or cognition systemic conditionsystemic condition substance-induced conditionsubstance-induced condition

Six Diagnostic Criteria for Dementia  5.Deficits do not occur exclusively during the course of a delirium  6.Disturbance is not better accounted for by another Axis I disorder (major depression, schizophrenia )

Mild Dementia  Disorientation for dates  Naming difficulties (anomia)  Recent recall problems  Difficulty copying figures  Decreased insight  Social withdrawal  Irritability, mood changes  Problems managing finances

Moderate Dementia  Disoriented to date and place  Comprehension difficulties  Impaired new learning  Getting lost in familiar areas  Impaired calculating skills  Delusions, agitation, aggression  Stop cooking, shopping, banking  Restless, anxious, depressed  Problems with dressing, grooming

Severe Dementia  Unintelligible speech  Remote memory gone  Inability to copy or write  Loss of self care  Incontinent

Clinical Features  Alzheimer’s Dementia Age: Age: Cognition: Memory Impairment Cognition: Memory Impairment Behavioral: Apathy, Depression Behavioral: Apathy, Depression Neurological: Intact Neurological: Intact Prognosis: Death 8-10 years Prognosis: Death 8-10 years

Clinical Features  Cerebrovascular Dementia Age: 70 Age: 70 Cognition: Language, Memory, Executive Function Impairment Cognition: Language, Memory, Executive Function Impairment Behavioral: Agitation, Hallucinations, Depression Behavioral: Agitation, Hallucinations, Depression Neurological: Frontal Release Signs, Neurological: Frontal Release Signs, (+) Brain Imaging Studies Prognosis: Death 5-8 years Prognosis: Death 5-8 years

Clinical Features  Lewybody Dementia Age: 65 Age: 65 Cognition: Memory, Executive Function & Orientation Impairment Cognition: Memory, Executive Function & Orientation Impairment Behavioral: Visual Hallucinations, Depression Behavioral: Visual Hallucinations, Depression Neurological: Parkinsonism Neurological: Parkinsonism Prognosis: Death 6-8 years Prognosis: Death 6-8 years

Clinical Features  Frontotemporal Dementia Age: 65 Age: 65 Cognition: Executive Function Impairment Cognition: Executive Function Impairment Behavioral: Social Inhibition Behavioral: Social Inhibition Neurological: Intact Neurological: Intact Prognosis: Death 6-8 years Prognosis: Death 6-8 years

Clinical Features  Parkinson’s with Dementia Age: 70 Age: 70 Cognition: Memory, Executive Function, Language, Orientation Impairment Cognition: Memory, Executive Function, Language, Orientation Impairment Behavioral: Depression, Hallucinations Behavioral: Depression, Hallucinations Neurological: Parkinson’s Disease Neurological: Parkinson’s Disease Prognosis: Death <5 years Prognosis: Death <5 years

Assessment Methods  Informant interview and office evaluation are the most important diagnostic tools  Functional Status: MMSE, Functional Activities Questionnaire (FAQ), Geriatric Depression Screening, Clock Drawing Test  Laboratory: CBC, CMP, TSH, Serology for Syphilis, Vitamin B12, HIV Core Geri, 2005

Assessment Methods  Brain Imaging (CT, MRI, PET) atrophy atrophy space-occupying lesions space-occupying lesions vascular disease vascular disease whiter matter disease whiter matter disease

Assessment Methods  Imaging Studies Order if-- Order if-- onset before 60 yrsonset before 60 yrs post-acute illness less that 18 monthspost-acute illness less that 18 months neurologic finding are asymmetricneurologic finding are asymmetric gait disturbancegait disturbance incontinence unexplainedincontinence unexplained

Treatment and Management  Goal: Enhance quality of life, maximize function, improve cognition, mood and behavior non-pharmacological non-pharmacological pharmacological pharmacological

Nonpharmacologic  Cognitive Enhancement reality orientation and memory training reality orientation and memory training  Individual and Group Therapy emotional orientated psychotherapy emotional orientated psychotherapy stimulation orientated therapy stimulation orientated therapy art and exercise

Other Nonpharmacologic  Communication with family and caregiver  Medical and legal Advance Directives  Environmental Modifications moderate stimulation only moderate stimulation only memory measures memory measures clocks, calendars, to-do lists name tags, alert bracelets

Pharmacologic  Individualized treatment  Monitor renal clearance and hepatic metabolism  Anticholinergic medications worsen cognitive impairment  “Start low and go slow”  Avoid starting multiple medications

Pharmacologic  Alzheimer’s Dementia Cholinesterase Inhibitors Cholinesterase Inhibitors Donepezil (Aricept)Donepezil (Aricept) Galantamine (Razadyne)Galantamine (Razadyne) Rivastigmine (Exelon)Rivastigmine (Exelon) Memantine (Namenda) Memantine (Namenda) SSRI’s SSRI’s

Pharmacologic  Cerebrovascular Dementia Cholinesterase Inhibitors Cholinesterase Inhibitors Control lipids Control lipids Stoke prevention Stoke prevention SSRI’s SSRI’s Memantine Memantine Anticonvulsants Anticonvulsants Antipsychotics Antipsychotics

Pharmacologic  Frontotemporal Dementia No Cholinesterase Inhibitors No Cholinesterase Inhibitors SSRI’s SSRI’s Memantine Memantine Anticonvulsants Anticonvulsants Antipsychotics Antipsychotics

Pharmacologic  Lewybody Dementia (Pick’s disease) Cholinesterase Inhibitors Cholinesterase Inhibitors SSRI’s SSRI’s Memantine Memantine Levodopa/ Carbidopa Levodopa/ Carbidopa Antipsychotic Antipsychotic

Pharmacologic  Parkinson’s Disease with Dementia Treat the Parkinson’s disease Treat the Parkinson’s disease No Cholinesterase Inhibitors No Cholinesterase Inhibitors SSRI’s SSRI’s Memantine Memantine Antipsychotic Antipsychotic

Cholinesterase Inhibitors  Donepezil (Aricept) Precautions: Nausea, vomiting, diarrhea, Precautions: Nausea, vomiting, diarrhea, GI bleed, sick sinus syndrome, seizures Interactions: CYP2D6 (flecainide, metopropol, codeine), used with NSAID 3-4x risk for GI bleed Interactions: CYP2D6 (flecainide, metopropol, codeine), used with NSAID 3-4x risk for GI bleed

Cholinesterase Inhibitors  Galantamine (Razadyne) Precautions: AV block, seizures, bladder obstruction, renal and hepatic, GI bleed, Precautions: AV block, seizures, bladder obstruction, renal and hepatic, GI bleed, GI upset Interactions: CYP3A4 (cholinergic agonist - bethanechol, ketoconazole, cimetidine, erythromycin) Interactions: CYP3A4 (cholinergic agonist - bethanechol, ketoconazole, cimetidine, erythromycin)

Cholinesterase Inhibitors  Rivastigmine (new q 24 Exelon Patch) Precautions: Nausea, vomiting, anoxia, Precautions: Nausea, vomiting, anoxia, GI bleed, sick sinus syndrome, seizures GI bleed, sick sinus syndrome, seizures Interactions: CYP2D6 and CYP3A4, potentates muscle relaxants, used with NSAID 3-4x risk for GI bleed Interactions: CYP2D6 and CYP3A4, potentates muscle relaxants, used with NSAID 3-4x risk for GI bleed

NMDA [glutamate] antagonist  Memantine (Namenda) Precautions: Dizziness, headache, alkalinized urine (ATN, UTI) seizures, GI upset Precautions: Dizziness, headache, alkalinized urine (ATN, UTI) seizures, GI upset Interactions: Other NMDA antagonists (amantadine, dextromethorphan), decreased by renally-excreted drugs (HCTZ) Interactions: Other NMDA antagonists (amantadine, dextromethorphan), decreased by renally-excreted drugs (HCTZ)

Mild to Moderate Dementia  Cholinesterase Inhibitors slow cognitive decline  Meta Analysis - Delayed nursing home placement by 1.2 years NNT 9.6NNT 9.6www.aoa.dhhs.gov

Moderate to Severe  Memantine: 1-3 year delay in progression of symptoms NNT 16.2 NNT 16.2  Memantine + Cholinesterase inhibitor No definitive data No definitive data early combination may decrease progression from mild to severe dementia by 4-5 years Ann Intern Med, 2004early combination may decrease progression from mild to severe dementia by 4-5 years Ann Intern Med, 2004

Research: What’s New  Tramiprostate (Alzhemed) mechanism: Inhibits GAG & Aβ protein fibrillizationmechanism: Inhibits GAG & Aβ protein fibrillization reduces amyloid formation and accumulationreduces amyloid formation and accumulation  Tarenflurbil (Flurizan) r-flurbiprofenr-flurbiprofen mechanism: Selective Amyloid-Lowering Agent (SALA)mechanism: Selective Amyloid-Lowering Agent (SALA) inhibits Aβ42 amyloid plaques cascadeinhibits Aβ42 amyloid plaques cascade  Alzheimer’s Vaccine

Research  Other studies estrogen estrogen NSAIDS NSAIDS vitamin E (increase cardiac events) vitamin E (increase cardiac events) selective monoamine oxidase-B inhibitor selective monoamine oxidase-B inhibitor ginko biloba ginko biloba prophylaxis cholinesterase treatment prophylaxis cholinesterase treatment J Gerontol a Bio Sci Med, 2004

Antidepressants  Guidelines (American & UK Geriatric Society) treating all patients with dementia and signs of depression/ anxiety with an SSRI or SNRI treating all patients with dementia and signs of depression/ anxiety with an SSRI or SNRI

All SSRI are not Equal  Paroxetine (Paxil): Drug interaction, anti-cholinergic  Fluoxetine (Prozac): Long half life, anorexia  Sertraline (Zoloft): Good, sleepy  Citalopram (Celexa): Good, mild hypotension  Escitlopram (Lexapro): Good, mild hypotension

“Sundowning”  Mild Dementia late afternoon or evening confusion late afternoon or evening confusion  Severe Dementia agitation, irritability restlessness agitation, irritability restlessness

“Sundowning”  Etiology: lack of clues from light/ dark cycling lack of clues from light/ dark cycling decrease sensory input decrease sensory input environmental changes environmental changes lack of a structure daily routine lack of a structure daily routine change in caregivers change in caregivers

“Sundowning”  Recommendations R/O occult medical problems R/O occult medical problems infectioninfection medication changesmedication changes avoid dramatic changes in living environment avoid dramatic changes in living environment encourage familiar home surroundings encourage familiar home surroundings

Key Points  Interviews & office evaluations are the most important diagnostic tools  Goal: Enhance quality of life, maximize function, improve cognition, mood and behavior  Not all SSRI’s are equal  Individualized treatment mild - moderate: cholinesterase inhibitors, mild - moderate: cholinesterase inhibitors, SSRI’s SSRI’s moderate - severe: memantine, SSRI’s or combinations moderate - severe: memantine, SSRI’s or combinations

References  Cobb, Duthie, Murphy; Geriatric Review Syllabus: A Core curriculum in Geriatrics, 5th ed, 2005,  Peterson, Smith, Waring, Mild Cognitive Impairment, Arch Neurol., 2005(3):  Royall, Chaiodo, Polk, Subclinical Cognitive Impairment, J Gerontol a Bio Sci Med, 2004;55 (9):M541-M546  Grifford, Holloway, Frankel, Improving adherence to dementia, A randomized Controlled Trial, Ann Intern Med, 2004;131(40):  Governmental Administration on Aging & Research  Alzheimer Research Forum,

Assessment: PET Alzheimer's Disease Alzheimer's Disease Parietal & Temporal deficits with intact neurologyParietal & Temporal deficits with intact neurology Frontotemporal Frontotemporal Frontal & Temporal deficitsFrontal & Temporal deficits Parkinson’s with dementia Parietal deficits Vascular dementia Focal, asymmetric