What is Alzheimer's? David Cravens, MD, MSPH, CMDPresentation Transcript
What is Alzheimer’s? David Cravens, MD, MSPH, CMD Assistant Professor U of Mo. School of Medicine Medical Director – Lenoir Healthcare
A condition that damages several parts of the brain
Accounts for the majority of dementia cases
Alzheimer’s Type Dementia (50-75 % of cases)
Vascular dementia (10 to 20 %)
Dementia with Lewy bodies (10 to 15 %)
Frontotemporal dementia (5 to 15 %)
Atypical Features that Suggest a Diagnosis Other than Alzheimer's Disease from Kawas CH. Early Alzheimer's disease. N Engl J Med 2003;349:1058. Progressive supranuclear palsy, Wernicke's encephalopathy Eye-movement abnormalities Parkinsonian syndromes, vascular dementia Extrapyramidal signs or gait Delirium due to infection, medications, or other causes; dementia with Lewy bodies Hallucinations or delusions Delirium due to infection, medications, or other causes; dementia with Lewy bodies; seizures Prominent fluctuations in levels of consciousness or cognitive abilities Vascular dementia, hydrocephalus Progressive gait disorder Frontotemporal dementia, vascular dementia Prominent aphasia Frontotemporal dementia Profound apathy Frontotemporal dementia Prominent behavior changes Vascular dementia Stepwise deterioration Vascular dementia Abrupt onset Diagnostic consideration Feature
Figure 1. Scans of Patients with Probable Alzheimer's Disease. In Panel A, a magnetic resonance image shows cortical atrophy and ventricular enlargement. In Panel B, a positron-emission tomographic scan shows reduced glucose metabolism in the parietal lobes bilaterally (blue-green) as compared with more normal metabolism in other cortical areas (yellow). NEJM.Volume 351:56-67 July1,2004. Number 1 Normal aging http://www.med.harvard.edu/AANLIB/cases/caseNA/pb9.htm
Prevalence & Incidence of SDAT
2.3 million (range, 1.09-4.8 million).
Doubles every 5 years after the age of 60
1% among those 60- to 64-years-old
Up to 40% of those aged 85 years and older
More common among women than men by a ratio of 1.2 to 1.5
Direct costs for the care of patients in 1991 were calculated at US $20.6 billion
Total cost was calculated to be $76.3 billion
Most direct costs of care for patients with AD are absorbed by the expense of nursing home care, approximately $47,000 per patient per year.
Age, Female sex
Most potent risk factor - presence of the apolipoprotein ( APOE 4) allele.
Lifetime risk of AD for an individual
without the 4 allele is approximately 9%
carrying at least 1 4 allele is 29%
4 genotype is not sufficiently specific or sensitive for the diagnosis of AD to allow its use as a diagnostic test
Other Risk Factors
Low serum levels of folate and vitamin B12
Elevated plasma and total homocysteine levels
Family history of AD or dementia
Fewer years of formal education
Lower occupational status
Lower Risk of AD
Higher levels of education
Moderate levels of daily wine consumption
Higher levels of fish in the diet
Differences in the prevalence of AD among population groups worldwide suggest as yet undisclosed genetic or environmental effects on the prevalence of AD
Putative Amyloid Cascade.
This hypothesis of the amyloid cascade, which progresses from the generation of the beta-amyloid peptide from the amyloid precursor protein, through multiple secondary steps, to cell death, forms the foundation for current and emerging options for the treatment of Alzheimer's disease. APP denotes amyloid precursor protein, and A beta-amyloid.
Cognitive impairment severe enough to cause social or occupational disability in at least two domains
8 years average. Range – 2-20 years
Orientation to time
Orientation to place
Attention & Calculation
Specificity is good (96%)
But the sensitivity is poor (63%)
Using a standard cutoff score of 24 will leave a substantial proportion of cases of early dementia undetected.
Asking patients and knowledgeable informants about deficits may enhance detection of early stages of AD
abnormalities in learning and retaining new information
difficulty handling complex tasks
impaired reasoning ability
changes in language or behavioral alterations
Typical Clinical Syndrome of AD
Amnestic type of memory defect
difficulty learning and recalling new information
Progressive language disorder
beginning with anomia and progressing to fluent aphasia
Disturbances of visuospatial skills
manifested by environmental disorientation and
difficulty copying figures in the course of mental status examination
Typical Clinical Syndrome of AD
There are usually deficits in executive function
The patient is typically unaware of memory or cognitive compromise.
All cognitive deficits progressively worsen.
Copyright restrictions may apply. Cummings, J. L. et al. JAMA 2002;287:2335-2338. Morphology and Distribution of Neuritic Plaques and Neurofibrillary Tangles Pathologic diagnosis of AD require the presence of both neuritic plaques and neurofibrillary tangles in excess of the abundance anticipated for age-matched healthy controls. Neuritic plaques consist of a central core of amyloid protein surrounded by astrocytes, microglia, and dystrophic neurites often containing paired helical filaments. Neurofibrillary tangles are the second major histopathological feature of AD. They contain paired helical filaments of abnormally phosphorylated tau protein that occupy the cell body and extend into the dendrites
Treatments for AD (Aricept) (Exelon) (Reminyl) (Namenda)
Treatments for AD
Vitamin E (2000 IU/d) and selegiline (10 mg/d) have been shown to reduce the rate of decline of functions in patients with AD.
Combined therapy was not superior to either agent alone.
Evidence to support the use of other antioxidants, anti-inflammatory agents, or herbal medications such as ginkgo biloba is insufficient to recommend use as standard therapies.
Estrogen in standard doses has been shown not to improve cognition in postmenopausal women with AD
Primary Efficacy Variables.
The mean (±SE) scores at each specified time in the observed-cases analysis are shown. The boxes indicate the mean (±SE) at the end point in the analysis with the last observation carried forward in the intention-to-treat population. Panel A shows the change from base line in the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) global scores. Panel B shows the change from base line in the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, modified for severe dementia (ADCS-ADLsev).
NEJM Volume 348:1333-1341 April 3, 2003. Number 14
Reducing amyloid production, aggregation, or enhancing its removal are promising avenues of treatment that will address the basic pathophysiology of AD.
Immunization, secretase inhibition, and other strategies to accomplish this are being studied.
Epidemiologic data suggest that some agents may decrease the likelihood of developing AD.
nonsteroidal anti-inflammatory agents
histamine H2 blockers
Clinical trials of these compounds to test their roles in the treatment or prevention of AD are planned or under way.
Building an alliance with family caregivers is critical to success in the management of patients with AD.
Family caregivers provide most of the care received by patients with AD over the course of their illness and are responsible for ensuring adherence to treatment regimens.
Caregivers are prone to depression and physical illness as a result of the chronic stress associated with caregiving.
Families benefit from short-term education programs and support groups.
The Alzheimer's Association is an important ally in identifying and providing community resources for patients with AD and their caregivers.
Rate of Death from Alzheimer's Disease and Costs Associated with Depression in Family Caregivers, 1979 through 1998. Age-adjusted, population-based death rates were obtained from the National Center for Health Statistics, Centers for Disease Control and Prevention. The number of caregivers of patients who had Alzheimer's disease and were in the last year of life was estimated on the basis of the death rate among patients with Alzheimer's disease, under the conservative assumption of one family caregiver for each patient who died. The prevalence of depression among caregivers of patients with end-stage Alzheimer's disease is 42.9 percent, as estimated by Schulz et al. The costs associated with depression were derived from estimates reported by Chisholm et al.,1 under the assumption that the cost per case is the same in all years after adjustment for inflation. NEJM Volume 349:1891-1892 Nov.13, 2003.