DEMENTIA IS A LOSS OF INTELLECTUAL FUNCTION. IT IS A BROAD TERM USED TO DESCRIBE A CONDITION WHERE A PERSON EXHIBITS IMPAIRMENTS IN HIGHER CORTICAL FUNCTIONS (language, orientation, perception, agnosias, aprexias, etc), IMPAIRMENTS IN SHORT-TERM MEMORY, WITH OR WITHOUT BEHAVIORAL /PERSONALITY CHANGE IN THE SETTING OF A NORMAL LEVEL OF CONCIOUSNESS.

DEMENTIA INCIDENCE: About 1-2%/year (Individuals 65 years or greater) AGE RELATED: yrs.: 0.13% yrs.: 0.74% >80 yrs.: 2.17%

DEMENTIA PREVALENCE: About % (Individuals 65 years or greater) AGE RELATED: yrs.: about 1% yrs.: about 5-9% yrs.: about 10-15% >85 yrs.: about 50% OVERALL: 4-5 Million: ALABAMA 79,000

OTHER FACTS ABOUT ALZHEIMER’S DISEASE 1 in 8 people (13%) have AD ½ million cases/yr by 2010; 1 million/yr by case every 77 sec.; by every 33 sec. Fifth case of death in people older than 60 Morality rate increased by 45% between 2000 and 2005, while it decreased for heart disease, stroke, prostate and breast cancer

OTHER FACTS ABOUT ALZHEIMER’S DISEASE Direct cost to Medicare/Medicaid and indirect costs to businesses with employees who are caregivers was $148 billion annually. In 2000, Medicare cost for AD was 3 time higher than for other illnesses ($13,000 vs $4,500) In 2007, 10 million Americans 18 yrs and older provided 8.4 billion hrs. of unpaid care ($89 million), 4 times what Medicare pays for nursing home care

DEMENTIA PHYSICIAN’S OBLIGATION  DIAGNOSIS  MANAGE  EDUCATE  RECOGNIZE

DEMENTIA MAKING THE DIAGNOSIS  HISTORY OF MEMORY PROBLEM  DOCUMENTATION OF MEMORY PROBLEM  NEUROLOGICAL EXAMINATION

DEMENTIA COGNITIVE IMPAIRMENT  MINI-MENTAL STATE EXAM  CATEGORY GENERATION  MATH  REASONING  LANGUAGE  SPATIAL ABILITIES

DEMENTIA COGNITIVE IMPAIRMENT  MINI-MENTAL STATE EXAM  ORIENTATION: 10 POINTS  IMMEDIATE RECALL: 3 POINTS  ATTENTION: 5 POINTS  DELAYED RECALL: 3 POINTS  HIGHER COGNITIVE FUNCTION: 9 POINTS

DEMENTIA COGNITIVE IMPAIRMENT  MINI-MENTAL STATE EXAM  CATEGORY GENERATION  MATH  REASONING  LANGUAGE  SPATIAL ABILITIES

DEMENTIA POTENTIALLY REVERSIBLE CAUSES  STRUCTURAL BRAIN LESIONS  METABOLIC DISORDERS  CNS INFECTIONS  PSYCHIATRIC ILLNESSES  SUBSTANCE ABUSE  MEDICATIONS

DEMENTIA IRREVERSIBLE CAUSES  ALZHEIMER’S DISEASE  DIFFUSE LEWY BODY DISEASE  FRONTO-TEMPEROL DEMENTIA  PARKINSON’S DISEASE  VIRAL AND PRION INFECTION  MULTIPLE STROKES  OTHER

DEMENTIA LABORATORY EVALUATION  BLOOD COUNTS & CHEMISTRIES  THYROID PANEL, B12, RPR  CRANIAL IMAGING (CT/MRI)  ?PET/SPECT  NEUROPSYCH. TESTING  ?LP?  PSYCHIATRIC EVALUATION

Figure 2. MRI in(a) normal, (b) mild Alzheimer's disease, and (c) moderate Alzheimer's disease subjects, showing medial temporal atrophy, which is worse on the left in subject (b). MRI OF AD

PET SCAN AD PET SCAN AD

ALZHEIMER’S DISEASE EARLY PHASE  SHORT TERM MEMORY LOSS  LANGUAGE DIFFICULTY (naming)  PSYCHIATRIC DISTURBANCES (irritability/personality change)  PRESERVATION OF SOCIAL GRACES  SUPERIFCIALLY APPEAR NORMAL

ALZHEIMER’S DISEASE MIDDLE PHASE  INREASING INTELLECTUAL FAILURE  INCREASING APRAXIAS  SOCIAL WITHDRAWAL  INCREASING MEMORY PROBLEMS  INCREASING LANGUAGE PROBLEMS  SPATIAL & VISUAL AGNOSIAS  BEHAVIORAL PROBLEMS

ALZHEIMER’S DISEASE LATE PHASE  LOSS OF RECOGNITON OF SELF & ENVIRONMENT  CHAIR/BED BOUND  DOUBLY INCONTINENT  FEEDING DIFFICULTIES  MUTE

ALZHEIMER’S DISEASE ATYPICAL PRESENTATIONS  DOMINANT HEMISPHERE: APHASIA WORD FINDING & HESISTENCY PARAPHASIAS & NEOLOGISMS  NON-DOMINANT HEMISPHERE: DRESSING APRAXIA VISUAL AGNOSIAS CONSTRUCTIONAL APRAXIA

ALZHEIMER’S DISEASE OTHER SIGNS & SYMPTOMS  PARKINSONISM  SEIZURES  MYOCLONUS

ALZHEIMER’S DISEASE CRITERIA FOR DIAGNOSIS  DEFINITE: Requires Clinical and Brain tissue  PROBABLE: 6 Month Hx of Cognitive Decline; STM loss; Loss in at least 2 other Cognitive Domains; Functional Impairment at Work or Home; No other Illness know to cause Dementia  POSSIBLE: Atypical Presentation or Progression; Only 1 Cognitive Domain affected; Other illness known to cause Dementia but not felt to be the cause (i.e. B12 deficiency)

ALZHEIMER’S DISEASE PATHOLOGICAL CHANGES  VULNERABLE AREAS Hippocampus Association Cortex Amygdala Nucleus Basalis Locus Cerulerous Raphe Nuclei

ALZHEIMER’S DISEASE MICROSCOPIC PATH.  NEUROFIBILLARY TANGLE  NEURITIC PLAQUE  AMYLOID PROTEINS

APP METABOLISM

ALZHEIMER’S DISEASE PATHOLOGICAL MECHANISMS  AMYLOID HYPOTHEISIS  NEUROFIBILLARY TANGLE HYPOTHESIS  FREE-RADICAL MECHANISMS  INFLAMMATORY MECHANISMS  CHOLINERGIC LOSS  CHOLESTREROL/ STATINS?

ALZHEIMER’S DISEASE RISK FACTORS  AGE 1% Population over Age 65 5% at Age % at Age 80 and Over  FAMILY HISTORY Autosomal Dominant Transmission Increased Risk for 1 O Relatives  DOWN’S SYNDROME All get Pathological Changes of AD ; 30-50% develop Dementia

ALZHEIMER’S DISEASE RISK FACTORS  GENDER More women than men: w/m  EDUCATIONAL LEVEL Lower education greater risk  VASCULAR RISK FACTORS Heart Healthy is Brain Healthy i.e. Hypertension and elevated Cholesterol are Risks for AD

ALZHEIMER’S DISEASE GENETICS  AUTOSOMAL DOMINANT TRANSMISSON  EARLY ONSET : <65 YEARS CHROMOSOME 1: Volga Germans; Presenilin 2 CHROMOSOME 14: 70%; Presenilin 1 CHROMOSOME 21: 5-10%  LATE ONSET: >65 YEARS CHROMOSOME 19 families

ALZHEIMER’S DISEASE GENETICS  APOLIPOPROTEIN E (Apo-E) 3 isoforms E1,2 & 3; E4 found in 50% of AD and only 10% of normals; Chromosome 19  MUTATIONS IN APP CHROMOSOME 21: Variety of point mutations

ALZHEIMER’S DISEASE MEDICATIONS  CHOLINESTERASE INHIBITORS Aricept (Donepezil) Exelon (Rivastigimine) Razadyne IR, ER (Reminyl; Galantamine)  NMDA RECEPTOR INHIBITORS Namenda (Memantine)

ALZHEIMER’S DISEASE CAREGIVERS  IDENTITY OF CAREGIVERS Spouse Adult Childern  SPECIAL STRESS Spouse : may be older in ill health; role reversals; increased work Adult Childern: often working; own family; childern

ALZHEIMER’S DISEASE CAREGIVER BURDEN  AD CAREGIVERS SPEND HRS/WK PROVIDING CARE  AD CAREGIVER REPORT MORE: 40 % MORE MD VISITS 70% MORE PRESCRIBED DRUGS MORE HOSPITALIZATIONS  50% AT RISK FOR DEPRESSION

ALZHEIMER’S DISEASE CAREGIVER ADJUSTMENT  DENIAL  OVER INVOLVEMENT  ANGER  GUILT  ACCEPTANCE

ALZHEIMER’S DISEASE PROFESSIONAL RESPONSIBILITIES  RECOGNIZE CAREGIVERS STRESS  ACKNOWLEDGE CAREGIVERS’ FEELINGS  REFER TO SUPPORT GROUPS  REFER TO PROFESSIONALS  PROVIDE EDUCATION  BE AVAILABLE