1. Alzheimer’s Disease The Challenge of Early Diagnosis Overview and Introduction

2. Benefits of Early Diagnosis and Treatment of Alzheimer’s Disease ► Alzheimer’s disease can be diagnosed approximately 90% of the time with a general medical and psychiatric evaluation 1,2 ► Early diagnosis has many advantages 3,4 l Allows time for planning l Empowers the patients to make treatment decisions early on l Facilitates caregiver participation ► May slow the progression of symptoms 2 ► Offers the patient potential for greater functioning and independence 2,3 ► Can help ease the stress for caregivers 2,3 Sources:1. Small GW, et al. JAMA. 1997;278:1363-1372. 2. National Institute on Aging. National Institutes of Health; 2000. NIH publication 00-4859:l-62. 3. Doraiswamy PM, et al. J Clin Psychiatry. 1998;59(suppl 13):6-18. 4. Knopman DS. In: Early Diagnosis of Alzheimer’s Disease. Totowa, NJ: Humana Press, Inc; 2000:298.

3. Discussion Points Dementia is underrecognized (even with behavioral symptoms) and undertreated ► 67.7% of residents* have dementia l Of those with dementia 73% were adequately evaluated 52% were adequately treated 70% had clinically significant behavioral symptoms Used 262 min/d of staff time vs no dementia 126 min/d (P<.005) *The results are based on a randomized cohort of assisted living (AL) residents of 22 randomly selected AL facilities in Baltimore and 7 Maryland counties. Source: Rosenblatt A, et al. J Am Geriatr Soc. 2004;52:1618-1625.

4. Barriers to Early Diagnosis Stigma ► First-degree relatives of AD patients reluctant to approve cognitive status examination ► Those of patients with more behavioral problems show greater reluctance Misconceptions ► Perception of uselessness of examination ► Perception of limited treatment options Early Stages Early Stages ► Patients maintain social skills in mild stages Source: Werner P, Heinik J. Int J Geriatr Psychiatry. 2004;19:479-486.

5. Barriers to Early Diagnosis (cont) Failure to Recognize the Importance of Cognitive/Functional Changes Racial Barriers ► Racial bias in screening tools ► Duality of respect for the patient— “normalization” ► Cultural ignorance or insensitivity Source: Cloutterbuck J, et al. Dementia. 2003;2:221-243.

6. Discussion Points Dementia Screening Tools: Effect of Ethnicity ► Brief screening tests often incorrectly classify African Americans with dementia (42%) compared to Caucasians (6%) ► The specificity of standardized cognitive assessments for dementia is particularly bad for African Americans ► Comparison of the utility of the Clock Drawing Test (CDT), Cognitive Abilities Screening Instrument, and MMSE l All tests were affected by education level l CDT was most sensitive to poorly educated non-English speakers Sources:Stephenson J. JAMA. 2001;286:779-780. Lampley-Dallas VT. J Natl Med Assoc. 2001;93:323-328. Fillenbaum G, et al. J Clin Epidemiol. 1990;43:651-660. Borson S, et al. J Gerontol A Biol Sci Med Sci. 1999;54:M534-M540.

7. Ethnic Differences in Knowledge and Perception of AD ► Elderly have misperceptions about the prevalence, etiology, diagnosis, and financial coverage for AD treatments ► Older Hispanic and Asian adults frequently consider AD a contagious but curable disease ► Hispanic, Asian, and African Americans more often consider AD a form of insanity ► Education levels partially explain differences in AD knowledge between Caucasians and Hispanics ► For Asians, the number of years speaking English is correlated with better knowledge of AD Source: Ayalon L, et al. Int J Geriatr Psychiatry. 2004;19:51-57. Discussion Points

8. Barriers to Early Diagnosis (cont) ► Barriers associated with PCPs ► Differential diagnosis l Vascular dementia, frontotemporal dementia, Lewy body dementia ► Comorbid conditions l Differentiating dementia, delirium, and depression ► Time l 1 hour required for diagnosis, but only 15 minutes reimbursed l Knowledge of appropriate reimbursement codes ► Overabundance of tests

9. Discussion Points Vascular Dementia (VaD) - Key Elements ► Cognitive impairment caused by cerebrovascular disease or cerebrovascular accident ► Mixed dementia = VaD + AD ► “Stairstep” progression of illness ► May have motor impairment early in the course of illness ► Care Notes l Treat hypertension, diabetes, ↑ lipids l May be associated with severe or refractory depression l Accommodate hemiplegia in interactions with staff/environment Source: Black SE. Postgrad Med. 2005;117(1):15-16,19-25.

10. Discussion Points Dementia With Lewy Bodies - Key Elements ► Wide fluctuations in cognition, responsiveness, and function ► Vivid visual hallucinations and paranoid delusions ► Parkinsonism occurs early ► Care notes l Some antipsychotics will cause severe parkinsonism at low doses l Quetiapine, aripiprazole, or clozapine may be tolerated best l Cholinesterase inhibitors are helpful l Levodopa and Parkinson’s disease medications have limited effectiveness for movement disorders Sources: McKeith IG, et al. Neurology. 1996;47:1113-1124. McKeith IG, et al. Neurology. 1999;53:902-905.

11. Discussion Points Frontotemporal Dementia - Key Elements ► Frontal lobe dementia, Pick’s disease ► Earlier age of onset than AD ► Gradual decline ► Early problems with memory and language expression ► Prominent personality changes—socially inappropriate, disinhibited, and compulsive (sexualized, eating) behaviors often observed ► Care notes l Cholinesterase inhibitors not very effective l Safe environment for harmful compulsive behaviors Source: McKhann GM, et al. Arch Neurol. 2001;58:1803-1809.

12. Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:142-143. Alzheimer’s Disease ► Multiple cognitive deficits, with both memory impairment and 1 or more of the following deficits: ● Aphasia (language) ● Apraxia (learned motor skills) ● Agnosia (visuospatial/sensory) ● Executive functioning (planning, insight anticipation) ► Impairment in social or occupational functioning, representing a significant decline from a previous level of functioning ► Gradual onset and progressive cognitive decline

13. Overcoming Barriers to AD Diagnosis ► Time l Schedule high-risk patients at end of day l AD does not have to be diagnosed in a single visit ► Reimbursement l Know appropriate codes for AD diagnosis and for extra time ► Coexisting illnesses l AD treatments may permit sustained self-management of other illnesses ► Depression l Evaluate patients using Geriatric Depression Scale (15 questions) ► Screening tools l Start slowly in gathering information, eg, MMSE (10-15 minutes) and CDT (1-5 minutes) l FAQ 10 questions completed by family

14. Targeted Screening ► Patients at least 65 years of age, when clinical presentation suggests the possibility of dementia (eg, forgetfulness, poor hygiene, poor compliance) ► All patients at least 80 years of age, with regular frequency Sources: Kaiser Permanente Care Management Institute. Guidelines for the diagnosis and management of dementia in primary care. Available at: http://members.kaiserpermanente.org/kpweb/pdf/feature/247clinicalpracguide/CMI_ DementiaGuideline_public_web_020604.pdf. Accessed August 17, 2005. Knopman DS, et al. Neurology. 2001;56:1143-1153. Screening assesses quantitative and objective measures rather than qualitative responses.

15. Discussion Points ► Is there a relationship between mild cognitive impairment (MCI) and AD? (16% of MCI patients convert to AD per year) ► How do we differentiate MCI from AD? ► Government recommendation not to screen (Agency for Healthcare Research and Quality)

16. The Case for Universal Cognitive Screening ► Memory complaints are common and can be associated with subsequent dementia ► Early dementia symptoms can be difficult to recognize ► Cognitive impairment affects how medical care is provided l Management (and costs) of other diseases l Follow through with medical recommendations l Prevention of complications

17. Discussion Points ► Which screening tools do you recommend? l A dialogue on the utility of screening tools ► Educational preceptorship—warning signs and public awareness l Community l Doctors l Consumers l Alzheimer’s Association

18. Dementia Diagnostic Process ► General screen l Signs of acute/chronic disease: how well controlled? l Common conditions l Weight loss, dehydration, subnutrition Include obstructive sleep apnea, insomnia, depression ► Neurologic screen l Vascular or Parkinson’s dementia, frontal signs l Gait, balance, and falls l Neuropathy ► Laboratory screen l Vitamin B 12 deficiency, hypothyroidism l Associated problems, secondary complications, and additional causes ► Brain structural screen l Noncontrast CT or MRI l Surgical and vascular lesions

19. Evaluation of the AD Patient ► In approximately 90% of patients who have AD, the diagnosis can be made on the basis of: l Detailed medical history obtained from the patient and a reliable informant l Medical examination l Mental status examination ► A 15-minute office visit is insufficient for fully evaluating the AD patient. For patients seen regularly, a 3-stage assessment may be more appropriate Source: Cefalu C, Grossberg GT. Diagnosis and Management of Dementia. American Family Physician Monograph, No. 2. Leawood, Kan: American Academy of Family Physicians; 2001.

20. The Office History ► Memory impairment: repetitive; trouble remembering recent conversations, events, appointments; frequently misplaces objects ► Executive impairment: deterioration of complex task performance; decreased ability to solve problems; impaired driving ► Drugs: alcohol, prescriptions, over-the- counter (OTC) medications ► Focal motor or sensory neurologic symptoms

21. ► Take comprehensive history l Medical history, medications (including OTC drug use) ► Interview immediate family member/caregiver ► If time permits and patient is cooperative, perform MMSE ► Assess family needs and caregiver stress First Visit Source: Cefalu C, Grossberg GT. Diagnosis and Management of Dementia. American Family Physician Monograph, No. 2. Leawood, Kan: American Academy of Family Physicians; 2001. Evaluation of the AD Patient (cont)

22. Second Visit ► CBC, electrolytes, LFTs, TSH, B 12, folate, UA, EKG, HIV, VDRL, ESR, homocysteine ► Neuroimaging ► Perform MMSE if not performed on first visit ► Reassess family needs and caregiver stress ► Consider neuropsychological testing CBC = complete blood count; LFTs = liver function tests; TSH = thyroid-stimulating hormone; UA = unstable angina; EKG = electrocardiogram; HIV = human immunodeficiency virus; VDRL = Venereal Disease Research Laboratory test; ESR = erythrocyte sedimentation rate. Source: Cefalu C, Grossberg GT. Diagnosis and Management of Dementia. American Family Physician Monograph, No. 2. Leawood, Kan: American Academy of Family Physicians; 2001. Evaluation of the AD Patient (cont)

23. ► Review laboratory findings and results of testing ► Discuss treatment options, follow-up plans for patient ► Readdress family and caregiver needs Third Visit Source: Cefalu C, Grossberg GT. Diagnosis and Management of Dementia. American Family Physician Monograph, No. 2. Leawood, Kan: American Academy of Family Physicians; 2001. Evaluation of the AD Patient (cont)

24. Discussion Points What Is the Place for Imaging? ► Noncontrast CT or MRI scan in the initial evaluation is appropriate (American Academy of Neurology Guideline) ► The use of positron emission tomography ► Value of imaging is to rule out other forms of intracranial pathology that may be contributing to cognitive change or for unusual presentations: l Rapid onset (duration <3 months), subdural hematoma, cerebral neoplasms, head trauma, history of cerebrovascular accident(s), seizures, new-onset urinary or fecal incontinence, abnormal gait, postural instability, focal signs, visual field deficit, headaches, suspect malignant tumor Sources: American Academy of Neurology. Neurology. 2001;56:1133-1142. American Academy of Neurology. Neurology. 2001;56:1143-1153.

25. Practical Consequences of Improved Diagnostic Accuracy ► Accurate diagnostic information and education reduce family/caregiver burden ► Decreased likelihood of repeated diagnostic assessments and testing ► “AD label” improves caregiver attitudes ► Information about the disease improves quality of life for family/patient and delays nursing home placement Sources: Mittelman M, et al. JAMA. 1996;276:1725-1731. Wadley V, et al. J Gerontol B Psychol Sci Soc Sci. 2001;56:P244-P252.

26. Stages of Alzheimer’s Disease Mild Moderate Severe Cognition Difficulty recognizing family and friends Chronic loss of recent memory Loss of speech Misidentifies or is unable to recognize familiar people Confusion and memory loss, eg: Needs help with basic ADL (eg, feeding, dressing, bathing) Progresses to total dependence on caregiver (eg, feeding, toileting) Problems with routine tasks Activities of daily living (ADL) Behavior Anxiety, suspicion, pacing, insomnia, agitation, wandering Crying, screaming, groaning Changes in personality – Misplacing objects – Forgetting names – Disorientation Sources: National Institute on Aging. National Institutes of Health; 2003. NIH publication 02-3782. Available at: http:www.alzheimers.org/unraveling/index.htm. Accessed January 10, 2005. Alzheimer’s Association. Available at: http://www.alz.org/AboutAD/Stages.asp. Accessed January 13, 2005.

27. Summary ► Marked changes in memory are not a normal part of aging and may signal a developing dementia ► Universal screening for AD is important ► Effective diagnosis and management take time l Three separate visits may be required ► It is important to recognize and overcome the barriers to early diagnosis of AD