Patient Identification and Initial Strategies

1. Patient Identification and Initial Strategies

2. Alzheimer’s Disease (AD): More Than Just Memory Loss AD is a progressive, degenerative disease involving: Loss of memory and other cognitive functions Decline in ability to perform activities of daily living Changes in personality and behavior Increases in resource utilization Eventual nursing home placement AD affects all aspects of life for both the patient and the caregiver AD affects all aspects of life for both the patient and the caregiver

3. Alzheimer’s Disease Overview Progressive, degenerative brain disease characterized by an increasing loss of memory & other cognitive functions Characterized by changes in activities of daily living (ADL), behavior & personality, cognition including judgment – ABCs Most common cause of dementia among people aged 65 or over

4. Current Prevalence of AD AD is the fourth leading cause of death due to disease for people > 65 years of age in the United States1 Approximately 4 million people in the United States have AD2

5. AD Is the Most Prevalent Type of Irreversible Dementia

6. Mortality Due to AD: Impact of Age

7. Cost of AD in the US Annual treatment costs ~ $100 billion $18,408/patient per year for mild AD $30,096/patient per year for moderate AD $36,132/patient per year for severe AD

8. Does Treatment Affect the Cost of AD? Savings are small for mild and very severe AD Prevention of even a small decline in cognition for patients with moderate AD would save ~ $3,700 per patient annually Relatively small improvements in patients with moderate AD would save ~ $7,100 per patient annually

9. Who Are the Caregivers? The overwhelming majority of patients live at home and are cared for by family and friends 77% are women 73% are over 50 years of age 33% are the sole providers 45% are children of the patient 49% are spouses Remainder are close family members or friends

10. Caregiver Burden Caregivers spend from 40–100 hours per week with the patient 90% are affected emotionally (frustrated, drained) 75% report feeling depressed; 66% have significant depression Half say they do not have time for themselves and that the stress affects family relations Many experience a significant loss of income This slide describes many of the stresses associated with caring for a patient with AD Some estimates of caregiver burden suggest that the caregiver is particularly affected by behavioral disturbances in the AD patient Many patients with AD suffer from depression; caring for a depressed patient is very likely to result in depression in the caregiver 1 study found that 100% of caregivers of depressed patients with AD also suffer from depression1 This slide describes many of the stresses associated with caring for a patient with AD Some estimates of caregiver burden suggest that the caregiver is particularly affected by behavioral disturbances in the AD patient Many patients with AD suffer from depression; caring for a depressed patient is very likely to result in depression in the caregiver 1 study found that 100% of caregivers of depressed patients with AD also suffer from depression1

11. Factors That Create “Breaking Point”for Caregiver Amount of time spent caring for the patient Loss of identity Patient misidentifications and clinical fluctuations Nocturnal deterioration of patient

12. Neuropathological ChangesCharacteristic of AD Widespread, diffuse atrophy with resulting ventricular enlargement is seen in AD brains, especially in later stages of the disease.Neurofibrillary tangles and amyloid plaques are the most distinctive neuropathological features of AD. Amyloid plaques begin in a diffuse form and mature into a compact, fibrillar form surrounded by dystrophic neurites and glial cells. In the photomicrograph of the left, a large plaque with a light staining core and dense staining halo is visible centrally.The photomicrograph on the right shows neurofibrillary tangles that contain abnormal cytoskeletal elements and appear as dense staining ‘flames’ within the neurones.Acetylcholine (ACh), 5-HT, and noradrenaline (NA) levels are decreased following neuronal losses in nucleus basilis of Meynert (ACh), nuclei of Raphe (5-HT) and nucleus caeruleus (NA). Immunoreactivity to substance P is also reduced. Widespread, diffuse atrophy with resulting ventricular enlargement is seen in AD brains, especially in later stages of the disease.

13. Key Risk Factors for AD Primary risk factors Age Family history Genetic marker such as APOE-4, trisomy 21, mutations in presenilin 1,2 Cardiovascular risk factors e.g. hyperlipidemia/hypertension (the role of statins and omega 3 fatty acids) Possible risk factors Head trauma Low level of education Depression Increased zinc? Increased homocysteine (the role of B-vitamins, e.g. Folic acid) Many risk factors for AD have been identified or proposed, but only age and family history of dementia are consistently associated in all studies. First-degree relatives of a patient with AD have a 2 to 4 times greater risk of developing the disease as compared with the general population. This increased risk may be linked to apolipoprotein e4 (APOE e4), an allele on chromosome 19, leading to the proposal that APOE status may be a genetic marker for AD. APOE e4 also appears to be associated with early-onset AD and more rapid declines of cognitive function. History of depression, as-yet-unidentified genes, previous head injury, and low education level may also be linked to susceptibility. Sources Caselli RJ, Graff-Radford NR, Reiman EM, et al. Preclinical memory decline in cognitively normal apolipoprotein E- epsilon4 homozygotes. Neurology. 1999;53:201–207. Emmerling MR, Morganti-Kossmann MC, Kossmann T, et al. Traumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann NY Acad Sci. 2000;903:118–122. Geerlings MI, Schmand B, Braam AW, et al. Depressive symptoms and risk of Alzheimer’s disease in more highly educated older people. J Am Geriatr Soc. 2000;48(9):1092–1097. Geerlings MI, Schmand B, Jonker C, et al. Education and incident Alzheimer’s disease: a biased association due to selective attrition and use of a two-step diagnostic procedure? Int J Epidemiol. 1999;28(3):492–497. Many risk factors for AD have been identified or proposed, but only age and family history of dementia are consistently associated in all studies. First-degree relatives of a patient with AD have a 2 to 4 times greater risk of developing the disease as compared with the general population. This increased risk may be linked to apolipoprotein e4 (APOE e4), an allele on chromosome 19, leading to the proposal that APOE status may be a genetic marker for AD. APOE e4 also appears to be associated with early-onset AD and more rapid declines of cognitive function. History of depression, as-yet-unidentified genes, previous head injury, and low education level may also be linked to susceptibility. Sources Caselli RJ, Graff-Radford NR, Reiman EM, et al. Preclinical memory decline in cognitively normal apolipoprotein E- epsilon4 homozygotes. Neurology. 1999;53:201–207. Emmerling MR, Morganti-Kossmann MC, Kossmann T, et al. Traumatic brain injury elevates the Alzheimer’s amyloid peptide A beta 42 in human CSF. A possible role for nerve cell injury. Ann NY Acad Sci. 2000;903:118–122. Geerlings MI, Schmand B, Braam AW, et al. Depressive symptoms and risk of Alzheimer’s disease in more highly educated older people. J Am Geriatr Soc. 2000;48(9):1092–1097. Geerlings MI, Schmand B, Jonker C, et al. Education and incident Alzheimer’s disease: a biased association due to selective attrition and use of a two-step diagnostic procedure? Int J Epidemiol. 1999;28(3):492–497.

14. AD Is Often Misdiagnosed Patient initially diagnosed with AD

15. Treatment Alternatives Symptoms Non-pharmacological Neuroleptics Anti-depressants Anti-convulsants ChEIs NMDA receptor antagonists

16. AD Treatment Algorithm Stage of AD Mild Moderate Severe Treatment Options ChEI ChEI/ Memantine Memantine (alone or in (alone or in combination) combination)