Early Identification and Management of Patients at Risk for Alzheimer’s
Disease:
A Patient-Centered Approach
Alzheimer’s disease (AD), an irreversible, degenerative, and eventually fatal brain disorder, is the most common cause of dementia.1 Based on middle series United States Census Bureau estimates, prevalence was estimated at 4.5 million people in 2000. Projecting to 2050, approximately 13.2 million Americans will be affected by this disease (Figure 1a) as the population of the oldest old grows through increased survival.2 Alarmingly, the incidence rate of AD at least doubles across 5-year age groups (Figure 1b).3
Figure 1. The epidemiology of Alzheimer’s disease2
a. Projected growth in the number of people with Alzheimer’s disease by age, based on the 2000 US Census Bureau middle series estimates
Figure 1. The epidemiology of Alzheimer’s disease3
b. The incidence rate of Alzheimer’s disease per 1000 person-years across 5-year age groups (% [95% CI])
While age is highly associated with the development of AD, there are several other predisposing risk factors. It is more common in women than in men, although this may reflect a longer life expectancy. Early onset AD has been linked to head trauma.4 An association between subclinical hyperthyroidism in the elderly and AD also has been recognized.5 People with lower educational levels have a higher risk of AD.6 Four genetic mutations—3 that promote increased β-amyloid production and are linked to early-onset AD, and apolipoprotein E (APOE) e4, a risk factor for late-onset AD—have also been implicated.7 Yet other possibilities are under investigation including the contributions of cardiovascular factors, diabetes, and obesity, along with a variety of lifestyle choices such as smoking and exercise.
Underdiagnosis
Unfortunately, because the symptoms of early AD are subtle, it often goes unrecognized and is dismissed as normal aging, particularly in people with mild functional impairment.8,9 The person with AD is unlikely to seek help for problems with cognition, behavior, or function, and may actually be unaware of or in denial about any difficulties. Family members may overlook changes in memory, behavior, and judgment, indeed adjusting their own responses to their loved one and compensating for any deterioration. This often results in a lag between the time the first symptoms of AD are recognized and the time that they are brought to the attention of a clinician. In turn, this initial consultation may be followed by another lag before the correct diagnosis is made.10,11
Inadequate training and experience in diagnostic procedures and the use of cognitive testing instruments hinder the primary care practitioner (PCP) in the early identification of AD. Despite the fact that a clinical diagnosis can be made accurately, many PCPs still believe that AD can only be diagnosed at autopsy. A further complication may be the presence of comorbidities that can mask AD, especially in the inpatient setting.11 A delay in diagnosis has considerable medical and social implications, and may result in a greater risk of earlier nursing-home placement.
Is Early Detection the Answer?
To answer an overarching question about screening, several other questions should be considered. Is there additional benefit to be gained by identifying people with cognitive impairment? Can any harm come from the process? Is it cost effective? The answer to these questions should be resoundingly positive.12 A commitment to early detection of AD will encourage PCPs to perform a more thorough assessment during which they can rule out potentially reversible causes of dementia and choose appropriate treatment-interventions in a timely manner. However, if AD is diagnosed, the initiation of a care plan and the early use of available medications may maximize cognition and the performance of activities of daily living at the highest level of functioning to preserve.13,14 By slowing the progression of symptoms, independent functioning can be prolonged, thereby lessening disease burden and allowing improved quality of life for both the patient and caregiver.
Early detection can also provide
significant social benefits, not least of which is a reduction in direct and
indirect costs of care. Eventually, most people with AD will require
round-the-clock care, either in the home or in a nursing home. Both options
involve substantial direct costs; however, treatment in the community or even
in an assisted-living facility is far less expensive than a nursing home.
Maintaining a patient at a higher level of functioning by treating early
reduces costs.15
By identifying Alzheimer’s disease in its earliest stage, both the patient and caregiver can plan for the future knowing that the person with AD is still capable of making informed decisions. Such plans might include estate planning, updating a will, and completing other legal documents; granting legal and medical power of attorney; establishing or setting up bank accounts; assigning a healthcare proxy who can make decisions about participation in clinical trials as well as see to it that end-of-life wishes regarding care and medical treatments are observed; and specifying advance directives, possibly in the form of a living will. All healthcare-related documents should be reviewed, and distributed to family members and healthcare providers. A checklist, like the one in Table 1, can be a helpful tool for the caregiver and patient to complete at this time.
Table 1. A Checklist for Important Papers
|
Check here |
Document |
Location |
|
|
Will |
|
|
|
Legal power of attorney |
|
|
|
Medical power of attorney |
|
|
|
Healthcare proxy |
|
|
|
Advance directives/living will |
|
|
|
Savings accounts and numbers |
|
|
|
Checking accounts and numbers |
|
|
|
Retirement accounts and numbers |
|
|
|
Stocks and bonds |
|
|
|
Credit cards |
|
|
|
Life insurance policy |
|
|
|
Health insurance |
|
|
|
Medicare |
|
|
|
Social Security |
|
|
|
Retirement papers |
|
|
|
Mortgage |
|
|
|
Deed |
|
|
|
Homeowner’s insurance |
|
|
|
Car title |
|
|
|
Car insurance |
|
|
|
Funeral arrangements |
|
Other critical issues should be handled during this time, as well. What are the options for housing now and in the future? What changes in the current home should be made to ensure safety? Can the patient and caregiver reach an understanding about important concerns such as driving, cooking, and medication adherence so that caregiver guilt will be diminished or alleviated when the inevitable need for intervention arises?
Arrangements can also be made for caregiver education, addressing not only how the disease can be expected to progress and how the patient can be managed at each stage, but what psychological effects AD can be expected to have on the caregivers. Such knowledge can not only help caregivers plan for future physical care for the patient, but can also promote awareness of support programs as well as services that can relieve caregiver burden and permit the caregivers to find time for themselves, apart from the patient. Some family members may also find relief in learning more about the likelihood of genetic inheritance of AD and in arranging genetic testing.
Can Alzheimer’s Disease Screening Become Routine in the Primary Care Practice?
In the context of the 15-minute primary care office visit with many patient complaints vying for attention,16 it is difficult to imagine how AD screening of patients 75-years and older can become routine. Perhaps screening should begin with greater awareness and sensitivity on the part of all care providers and office staff. If a known patient is answering questions in a way that arouses suspicion or if there have been changes in behavior, cognition, and ability to function over time, the PCP should be alerted to the need for further screening.
Many screening tools have been developed for AD. The ideal test used should be brief, easy to administer and score, free, and available on multiple platforms so that it can be used both in a PCP office and in the community setting. Bear in mind that the test is a tool that can draw attention to the need for more complete assessment. For years, the Mini-Mental State Examination (MMSE) was used extensively to assess patients in studies; however, some feel that it has poor sensitivity and specificity for screening, includes items that complicate the process rather than add necessary discriminatory information, and requires props.12
The AD8 approaches screening as an
informant interview, asking questions that elicit information about changes in
judgment, interests, memory, tool utilization, orientation, and financial
abilities. It has been used in conjunction with the Word List Recall to improve
AD detection.17 Patients also have completed it themselves in the
absence of reliable informants, though this is more successful in people who
have mild dementia than among those who are more severely affected.18
The Brief Alzheimer Screen (BAS), which includes 3-word recall, number of
animals named in 30 seconds, the date, and spelling of WORLD backwards, can
distinguish those people who have mild AD from those who have normal cognition,
with high sensitivity and specificity.19 Other screening tests such
as the Cognitive Screening Test have been designed to decrease the demands on a
PCP, are administered on the Internet, and require little in terms of
administration and interpretation.20
Know the 10 Signs (Table 2),21 part of an Alzheimer’s Association® public-outreach campaign to promote the early detection of AD, is similar in content to informant questionnaires. It can be a useful posting in a PCP office as it not only lists the signs of AD, but also contrasts these signs with normal behavior. This can help to alleviate confusion about what indeed is normal.
Table
2. Alzheimer’s Association Know the 10
Signs21
As might be expected, clinician and organizational opinions differ regarding the need for routine screening. However, recognizing the tremendous impact of AD on society, a recently convened panel of experts developed recommendations for best practices, including screening, in Medicare managed-care organizations. Their recommendation was that brief telephonic screening be conducted, particularly in people aged 75 years and older. They also supported brief in-office screening in this same age group and at any age if someone familiar with the patient notes confusion, memory loss, or any other symptoms of cognitive impairment.13
Making Screening Work
As discussed, in the busy PCP office, time and staff considerations affect the decision to screen. When possible, the use of trained nurses and allied health personnel to perform cognitive screenings or collect information from informants, who can complete questionnaires at their own convenience prior to the office evaluation, can reduce the demands on the PCP. This process frees the PCP for other elements of a full dementia examination if they are required.22
Who should be screened for memory problems and dementia? Patients under 75-years-old should be tested only if they complain of memory problems. At 75 years, baseline screening should be performed, particularly if there is a history of dementia in the family, if there is a known genetic abnormality, if the patient or family is concerned about changes, or if clinical or cognitive signs lead the PCP to suspect a problem. During this screening, history is obtained, systems are reviewed, and vital signs are taken. Follow-up is then at the discretion of the clinician based on degree of risk, or if the patient or family is concerned. After age 75 years, screening should take place every 2 years unless risk increases or concern is expressed. Thereafter, in the oldest old, those aged 85 years and older, screenings should be a part of the annual examination.
Diagnosing Alzheimer’s Disease
If dementia is suspected based on the screen, clinical risk factors, responses to questions, or changes over time, a full dementia assessment should be performed (Table 3).22-24 This assessment should include a more complete dementia-related history in which the patient and a family member or companion are queried about the presenting problem; the nature of memory problems and their onset; any unusual events around the time of their onset, including injuries, stress, and surgery; whether the symptoms have progressed; and how the symptoms have affected activities of daily living.
A complete medication review as well as physical and neurological examinations should be conducted, and a battery of laboratory tests ordered to rule out other forms of dementia. If indicated, the PCP may do an electrocardiogram or a chest X-ray. The assessment should also include tests for depression, cognitive function, and an informant questionnaire completed by a family member or companion who is familiar with the patient.
Table 3. Diagnosing Alzheimer’s Disease in the Primary Care Practice22-24
|
Full
Assessment |
Staff
Administrator |
|
Clinical history
with informant input |
PCP alone or with
nurse or clinical assistant |
|
Medication review
to rule out medication-related dementias |
PCP alone or with
nurse or clinical assistant |
|
Complete physical
examination to rule out other dementias |
PCP alone or with
nurse or clinical assistant |
|
Neurologic
examination to rule out other dementias · Cerebral, cerebellar, cranial nerve, and
motor-sensory function |
PCP alone or with
nurse or clinical assistant |
|
Laboratory tests
to rule-out other dementias · Complete blood count · Serum electrolytes · Glucose · Blood urea nitrogen/creatinine · Liver panel · B12, folate (consider
homocysteine) · Thyroid function · VDRL; HIV (if indicated) · Urinalysis |
PCP alone or with
nurse or clinical assistant |
|
Depression
screening test |
Trained medical
assistant or PCP |
|
Cognitive
assessment |
Trained medical
assistant or PCP |
|
Functional
assessment completed by caregiver |
Medical assistant
or PCP |
|
Interpretation of
all results |
PCP |
When to Refer
It is clear that genetic heritability is a risk factor for AD25; however, genetic testing is expensive and does not provide additional information to target therapy. Thus, genetic testing becomes a personal decision; if early-onset AD appears to run in a family, testing may be sought by the family. In a population survey of attitudes toward genetic testing for AD,26 79% of people said that they would pay for a completely predictive genetic test for AD. As shown in Figure 2,26 they stated that they would sign advance directives (84.3%), spend more time with family (80.1%), get finances in control (73.9%), and purchase long-term care insurance (69.3%) if testing was positive.
Figure 2. What people would do if they received a positive genetic test for Alzheimer’s disease26
A referral for anatomical neuroimaging with a noncontrast CT scan or noncontrast MRI should be made to rule-out strokes, tumors, subdural hematomas, and normal-pressure hydrocephalus. When possible, an MRI is preferable because of its greater accuracy. Although functional SPECT and PET scans can provide information, and are approved by Medicare to differentiate frontotemporal dementia from AD, they are recommended as an optional choice.13
Predicting the Risk of Dementia
Quite recently, an index to stratify older adults into low-, moderate-, or high-risk groups has been developed.27 This risk-assessment tool, evaluated in more than 3000 people without dementia who were participants in the Cardiovascular Health Cognition Study, used a point system based on age, poor cognitive test performance, body mass index, APOE e4, cerebral MRI findings, ultrasound of the carotid artery, history of bypass surgery, slow physical performance, and lack of alcohol consumption to predict the risk of developing dementia within 6 years. Its developers point to its potential in targeting prevention or intervention strategies.
Pharmacologic Interventions for Alzheimer’s Disease
The Food and Drug Administration has approved 4 cholinesterase inhibitors (CHEIs) for the treatment of mild-to-moderate AD: tacrine (1993), donepezil (1996), rivastigmine (2000), and galantamine (2001); however, tacrine is no longer marketed. Donepezil is the only CHEI that also has been approved in the treatment of severe AD. These agents have been approved in different formulations (Table 4): donepezil as an orally disintegrating tablet that is bioequivalent to donepezil tablets28; galantamine as an extended-release capsule29; and rivastigmine30 in oral solution and skin-patch formulations.
The rational for the use of this class of drugs is logical. Some of the signs and symptoms of AD have been attributed to a deficiency of cholinergic neurotransmission. By acting to reversibly block the degradation of acetylcholine by acetylcholinesterase, CHEIs increase the concentration of acetylcholine and enhance cholinergic function.28
Memantine, a noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist, was approved in 2003 for the treatment of moderate-to-severe dementia of the Alzheimer’s type. Theoretically, persistent activation of NMDA receptors by the excitatory amino acid, glutamate, may contribute to AD symptoms. Memantine acts as a low-to-moderate affinity noncompetitive NMDA receptor antagonist, binding preferentially to the NMDA receptor-operated cation channels.31
Table 4. Comparing Treatment Options for Alzheimer’s Disease28-31
|
Agent |
Indication |
Formulations |
|
Cholinesterase Inhibitors |
||
|
Donepezil |
Treatment of
mild-to-moderate and severe dementia of the Alzheimer’s type |
Tablets Orally
disintegrating tablets |
|
Galantamine |
Treatment of
mild-to-moderate dementia of the Alzheimer’s type |
Tablets Oral solution Extended-release
capsules |
|
Rivastigmine |
Treatment of
mild-to-moderate dementia of the Alzheimer’s type; treatment of dementia of
Parkinson’s disease |
Capsules Oral solution Transdermal patch |
|
NMDA Receptor Antagonist |
||
|
Memantine |
Treatment of
moderate-to-severe dementia of the Alzheimer’s type |
Tablets Oral solution |
The previously discussed consensus panel evaluated the use of approved antidementia therapies for AD and made recommendations for their use in clinical practice. Identifying levels of AD severity using MMSE scores, the panel divided patients into those with mild, moderate, severe, and profound disease. The panel evaluated the use of both the cholinesterase inhibitors and memantine, basing their recommendations on a combination of factors: FDA labeling, formulary policies of major organizations, and the application of these agents in practice.13
The Cholinesterase Inhibitors
The consensus panel pointed to similar effectiveness among the CHEIs. Figures 3 through 530,32-34 illustrate some of the changes in cognition and function seen with donepezil, galantamine, and rivastigmine. The effects of donepezil on cognition have also been studied in patients with early-stage AD. Significant improvement on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the MMSE were seen as early as 6 weeks after initiating therapy, indicative of its potential in maintaining independence in higher functioning patients.14
Other important distinguishing differences between the CHEIs were pointed out by the panel. Only donepezil is dosed at a clinically effective level initially; galantamine and rivastigmine require dose titration. Donepezil and galantamine are dosed once daily, as is the rivastigmine patch, with other formulations of rivastigmine dosed twice daily. Although the side effects profiles of the CHEIs were similar, rivastigmine may have a higher incidence of gastrointestinal adverse effects. The panel recommended that CHEI therapy should be the first choice in patients with mild AD and suggested that clinicians consider factors such as titration and tolerability in making their treatment decisions.13
Figure 3. Effects of donepezil on cognition and activities of daily living (ADL)32
a. Mean change in ADAS-Cog scores (ADAS-Cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale)
Figure 3. Effects of donepezil on cognition and activities of daily living (ADL)32
b. Mean change in quality of life (QoL) score
Figure 4. Effects of galantamine on cognition and behavior33
a. Mean change in ADAS-Cog (ADAS-Cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale) scores
Figure 4. Effects of galantamine on cognition and behavior33
b. Effects of galantamine on behavioral outcomes
Figure 5. Effects of rivastigmine on cognition and activities of daily living (ADL)30
a. Mean change in ADAS-Cog scores (ADAS-Cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale)
Figure 5. Effects of rivastigmine on cognition and activities of daily living (ADL)34
b. Mean change in Activities of Daily Living Progressive Deterioration Scale
Memantine
The panel recommended that patients who are first diagnosed with severe AD be treated with memantine. In a 28-week, double-blind, randomized, controlled study of memantine versus placebo in 252 patients with moderate-to-severe AD,35 outcomes significantly improved in the memantine arm on the Severe Impairment Battery and the Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia. However, there was no statistically significant improvement on the MMSE with memantine treatment compared to placebo (Figure 6).
Figure 6. Effects of memantine in the treatment of moderate-to-severe Alzheimer’s disease35
The panel also recommended combination therapy with a CHEI in patients with moderate AD,13 based on a 6-month trial comparing donepezil plus memantine versus donepezil plus placebo.36 This randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled 404 patients with moderate-to-severe AD who had been receiving stable doses of donepezil. Three hundred and twenty-two patients completed the trial, which evaluated changes on the Severe Impairment Battery (SIB), a test of cognition; a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL19); the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus); the Neuropsychiatric Inventory; and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale). There was significant improvement in all primary and secondary outcomes at Week 24 and at endpoint. Figure 736 shows improvements in cognition and ADL. In patients with mild AD, memantine was only recommended when a CHEI cannot be tolerated or in combination therapy when the disease is progressing rapidly.13
Figure 7. Effects of combination therapy with donepezil plus memantine on cognition and activities of daily living (ADL)36
The Future
Approaches that are directed at a multitude of potential pathways for the treatment of AD are in development. These include antiamyloid-based agents; changes to the structure of APOE e4; neuroprotective strategies; targeting the synapse, tangles, and other mechanisms of neuronal injury; and ideas for cognitive enhancement.37
Caring for the Caregiver
Anyone who has ever assumed full responsibility for a loved one can attest to the strain that it puts on both the relationship and the caregiver. Caring for a person with AD is fraught with difficulty, primarily as a result of the behavioral and psychological symptoms of dementia that run the gamut from apathy to aggression. Of course, the physical tasks of helping someone with activities of daily living such as bathing and dressing also can be daunting, particularly if the caregiver is of an advanced age. Seeing someone you have made a life with in a dependent state is difficult and caregivers may be at risk for depression or illness themselves.
Furthermore, caregivers often lack support and watch their world constrict until it revolves around the patient. To help a loved one, a person must make “me” time. The PCP can help to put the “I” into the caregiving process:
- Inform the caregiver about AD and what to expect at each stage. Explain its treatment and the effects of treatment on cognition, behavior, and performance of ADLs. Demystification and realistic expectations can reduce the stress that accompanies the unexpected.
- Include the caregiver in all discussions and in developing the plan of care.
- Inquire about the caregiver’s physical and mental well being, and look for signs of depression or illness.
- Identify helpful handouts, coping strategies, and support services.
- Improve quality of life. Encourage caregivers to make lists, ask questions, and communicate their needs. Often, they may require your help in discovering their own needs.
The resources available to caregivers have grown over the years. Books, pamphlets, and Web sites cover everything from positive thinking and managing stress to dealing with the day-to-day issues of AD care: wandering, communicating effectively, finding opportunities and places for respite care, safeguarding a home, long-distance caregiving, and making the transition to assisted living or nursing-home care. National and local organizations listed in the appendix can answer questions, provide opportunities for socialization, help with legal issues, and plan for a manageable future.
References
1. Alzheimer’s Association, 2009 Alzheimer’s disease facts and figures. Alzheimers Dement. 2009;5(3):234-270.
2. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Arch Neurol. 2003;60:1119-1122.
3. Kukull WA, Higdon R, Bowen JD. et al. Dementia and Alzheimer disease incidence. A prospective cohort study. Arch Neurol. 2002;59:1737-1746.
4. Van Duijn CM, Tanja TA, Haaxma R, et al. Head trauma and the risk of Alzheimer’s disease. Am J Epidemiol. 1992;135:775-782.
5. Kalmijn S, Mehta KM, Pols HAP, Hofman A, Drexhage HA, Breteler MMB. Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol. 2000;53:733-737.
6. Ott A, Breteler MB, van Harskamp F, et al. Prevalence of Alzheimer’s disease and vascular dementia: association with education. The Rotterdam study. BMJ. 1995;310:970-973.
7. 2007 Progress Report on Alzheimer’s Disease. US Department of Health and Human Services, National Institutes of Health, National Institute on Aging. NIH Publication Number: 08-6430, November 2008.
8. Sternberg SA, Wolfson C, Baumgarten M. Undetected dementia in community-dwelling older people: the Canadian Study of Health and Aging. J Am Geriatr Soc. 2000;48(11):1430-1434.
9. Fillit H, Geldmacher DS, Welter RT, Maslow K, Fraser M. Optimizing coding and reimbursement to improve management of Alzheimer’s disease and related dementias. J Am Geriatr Soc. 2002;50(11):1871-1878.
10. Knopman D, Donohue JA, Gutterman EM. Patterns of care in the early stages of Alzheimer’s disease: impediments to timely diagnosis. J Am Geriatr Soc. 2000;48(3):30-304.
11. Fillit HM. The pharmacoeconomics of Alzheimer’s disease. Am J Manag Care. 2000;6(suppl 22):S1139-S1144.
12. Ashford JW. Screening for memory disorders, dementia and Alzheimer’s disease. Aging Health. 2008;4(4):399-342.
13. Fillit HM, Doody RS, Binaso K, et al. Recommendations for best practices in the treatment of Alzheimer’s disease in managed care. Am J Geriatr Pharmacother. 2006;4(suppl A):S9-S24.
14. Seltzer B, Zolnouni P, Nunez M, et al, for the Donepezil “402” Study Group. Efficacy of donepezil in early-stage Alzheimer disease. Arch Neurol. 2004;61:1852-1856.
15. Rice DP, Fillit HM, Max W, Knopman DS, Lloyd JR, Duttagupta S. Prevalence, costs, and treatment of Alzheimer’s disease and related dementia: a managed care perspective. Am J Manag Care. 2001;7:809-818.
16. Tai-Seale M, McGuire TG, Zhang W. Time allocation in primary care office visits. Health Serv Res. 2007;42(5):1871-1894.
17. Galvin JE, Roe CM, Morris JC. Evaluation of cognitive impairment in older adults. Combining brief informant and performance measures. Arch Neurol. 2007;64:718-724.
18. Galvin JE, Roe CM, Coats MA, Morris JC. Patient’s rating of cognitive ability. Using the AD8, a brief informant interview, as a self-rating tool to detect dementia. Arch Neurol. 2007;64:725-730.
19. Mendiondo MS, Ashford JW, Kryscio RJ, Schmitt FA. Designing a Brief Alzheimer Screen (BAS). J Alz Dis. 2003;5:391-398.
20. Lichtenberg PA, Johnson AS, Erlanger DM, et al. Int J Healthcare Inform Syst Informat. 2006;1(3):47-57.
21. Alzheimer’s Association®. Know the 10 Signs. Available at: www.alz.org/national/documents/checklist_10signs.pdf. Accessed July 20, 2009.
22. Solomon PR, Murphy CA. Should we screen for Alzheimer’s disease. A review of the evidence for and against screening for Alzheimer’s disease in primary care practice. Geriatrics. 2005;60(11):26-31.
23. Christensen DD. Practical principles for the management of Alzheimer’s disease. Prim Care Companion J Clin Psychiatry. 2002;4:63-69.
24. Knopman DS, DeKosky ST, Cummings JL, et al. Practice parameter: diagnosis of dementia. Report of the Quality Standard Subcommittee of the American Academy of Neurology. Neurology. 2001;56(9):1143-1153.
25. Avramopoulos D. Genetics of Alzheimer’s disease: recent advances. Genome Med. 2009;1(3):34. [Epub ahead of print]
26. Neumann PJ, Hammitt JK, Mueller C, et al. Public attitudes about genetic testing for Alzheimer’s disease. Health Aff (Millwood). 2001;20(5):252-264.
27. Barnes DE, Covinsky KE, Whitmer RA, Kuller LH, Lopez OL, Yaffe K. Predicting risk of dementia in older adults. The late-life dementia risk index. Neurology. 2009 May 13. [Epub ahead of print]
28. Aricept [prescribing information]. Woodcliff Lake, NJ: Eisai Co., Ltd; 2006.
29. Razadyne [prescribing information]. Titusville, NJ: Ortho-McNeil-Janssen Pharmaceuticals, Inc.; 2008.
30. Exelon Patch [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009.
31. Namenda [prescribing information]. St. Louis, MO: Forest Pharmaceuticals, Inc.; 2007.
32. Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT, and the Donepezil Study Group. Neurology. 1998;50:136-145.
33. Tariot PN, Solomon PR, Morris JC, Kershaw P, Lilienfeld S, Ding C, and the Galantamine USA-10 Study Group. Neurology. 2000;54:2269-2276.
34. Potki SG, Hartman R, Veach J, Grossberg G. Impact of Alzheimer's disease and rivastigmine treatment on activities of daily living over the course of mild to moderately severe disease. Prog Neuropsychopharmacol Biol Psychiatry. 2002;26(4):713-720.
35. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ, for the Memantine Study Group. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003;348:1333-1341.
36. Tariot PN, Farlow M, Grossberg GT, Graham SM, McDonald S, Gergel I, for the Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil. A randomized controlled trial. JAMA. 2004;291:317-324.
37. Horton AR, Fillit HM. Drug discovery for Alzheimer’s disease: filling the pipeline. Curr Alz Res. 2007;4(5):501-502.
Appendix
The ABCs of Caregiver Resources
AARP
This non-profit group has tools, tips, and resources for a broad range of topics for people aged 50 years and older.
Alzheimer's Association
800 272 3900
This group supports families and caregivers of patients with Alzheimer's disease. Its Web site gives news and tips, and has many brochures that can be downloaded. Almost 300 local chapters can help people find assistance, aid in completing forms, or give locations for support groups.
Alzheimer's Disease Education and Referral (ADEAR) Center
800 438 4380
This government Web-site is funded by the National Institute on Aging. It provides news and updates on Alzheimer's diagnosis, treatment, care, caregiving and long-term care.
Alzheimer’s Foundation of America
866 232 8482
This agency provides care and services to individuals, caregivers, and families confronting dementia through member organizations.
Alzheimer’s Health Assistance Foundation (Click on Alzheimer’s Disease Research)
800 437 2423
This agency provides information, news updates, resources, and research grants in Alzheimer’s disease.
Benefits Check Up
This is a service of the National Council on Aging and enables the caregiver to determine benefits that the patient and caregiver might qualify for that can help in paying for prescription drugs, utility bills, meals, and health care.
Children of Aging Parents
800 227 7294
This organization provides information and materials for adult children caring for older parents.
Eldercare Locator
This government resource helps older people and caregivers find local support services.
Family Caregiver
Alliance
800 445 8106
This alliance offers caregiver support, including information about public policy and research, caregiver advice, fact sheets and publications.
Family Caregiving
101
Family Caregiving 101 helps with answers, new ideas, and advice for the caregiver.
Medicaid
www.cms.hhs.gov/home/medicaid.asp
This Web site provides information about a government program that pays for medical assistance for certain people with low incomes and resources.
Medicare
This Web site provides information about the federal health insurance program for people aged 65 years and older, and those with disabilities.
National Family Caregivers Association
800 896 3650
This organization helps educate and support people who care for loved ones with chronic illness, disability, or the frailties of old age. It has an online library, workshops, and other resources.
National Institute on Aging Information Center
800 222 2225
This government Web-site offers a wide range of information on health, aging, and NIA-sponsored research.
NIH Senior Health
This Web site features health and wellness information for older adults on a variety of topics.
National Resource
Center on Supportive Housing and Home Modifications
213 740 1364
This Web site promotes aging in place an independent living. It provides resources about home modifications.
The National Academy of Elder Law Attorneys
This Web site focuses on the legal needs of older people, providing educational resources. In addition, it can help the caregiver and elder law attorneys in their area.
The Simon Foundation for Continence
800 237 4666
This group helps people who have problems with incontinence, as well as their caregivers and healthcare providers. Books, pamphlets, tapes, self-help groups, and other resources are available.
Well Spouse Association
800 838 0879
Well Spouse is a membership group that supports the wives, husbands, and partners of the ill or disabled.