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Disease Severity at Diagnosis is Associated with Decreased Survival in Individuals Diagnosed with Alzheimer's Dementia

Disease Severity at Diagnosis is Associated with Decreased Survival in Individuals Diagnosed with Alzheimer's Dementia

Critique date: Wed, 01/12/2005 - 3:42pm
Institution: 
Mount Sinai School of Medicine
   
Article Citation
Citation: 
Larson E, Shadlen M, Wang L, McCormick W, Bowen J, Teri L and Kukull W. Survival After Initial Diagnosis of Alzheimer Disease. Ann Intern Med. 2004;140:501-509.
   
Clinical Bottom Lines
  1. Older adults diagnosed with Alzheimer's disease (AD) have diminished life expectancy compared to age-matched non-demented elders.
  2. Increased severity of cognitive impairment, decreased functional level, history of falls, presence of frontal release signs, abnormal gait, and medical comorbidity at AD diagnosis are all associated with reduced survival.
   
Methods
Type of Study: 
Prognosis
Follow-up Period: 
Survival known for all participants followed until time of death or 2001. Mean follow up was 5.2 + 3.1 years
Patient Population: 

N=521 community-dwelling adults >60 years (80% >75) enrolled in an Alzheimer's Disease (AD) patient registry (65.5% female) with newly diagnosed AD (431 probably, 90 possible) recruited between 1987-1996 from HMO clinics in Seattle and Western King County, Washington. 88% Caucasian

Inclusions

Presence of a newly developed dementia syndrome meeting DSM-IV criteria; consensus diagnosis for possible or probable AD

Significant Exclusions: 

Individuals with non-AD dementia or mixed dementias

Intervention/Exposure: 

A prospective observational study

Patients were followed over time. Baseline assessments of individuals' demographic features, MMSE score, Blessed Dementia Rating Scale score, duration from reported onset of symptoms, co-morbid conditions, and extra-pyramidal signs were collected via a questionnaire and examination. MMSE decline over the first year was also measured to assess whether a decline of 5 points or more on the MMSE in the first year post AD diagnosis was associated with reduced survival.

Outcome Measures: 

Survival time

   
Conclusion
Results: 
  • Patients with AD had significantly decreased survival compared with life expectancy of US population.
  • Median survival for men was 4.2 years; 5.7 years for women.
    • For women aged 70 with AD median survival was 8.0 years compared to 15.7.
    • For men aged 70 with AD median survival was 4.4 years compared to 12.4.
    • At older ages, the absolute survival difference between those with AD and the US population decreased
  • For women aged 85 with AD median survival was 3.9 yrs compared with 5.9.
    • For men aged 85 with AD median survival was 3.3 yrs compared with 4.7.
    • Men experienced poorer survival across all age groups compared to females.
  • Measures of severity of symptoms at the time of diagnosis (low MMSE, poor DRS) were the most powerful predictors of reduced survival.
    • Other independent risk factors included baseline frontal lobe release signs, baseline gait disturbance, history of falls, CHF, DM, history of ischemic heart disease.
  • A decline of >5 points on the MMSE after the first year of follow-up was associated with a 60% increase in death (adjusted HR 1.6-1.66 after adjustment for age, baseline MMSE, sex, ethnicity, ischemic heart disease, CHF, and DM).
Concerns Regarding Methodology, Applicability to Older Adults, etc.: 
  • This is a well-done study observing associations between disease and co-morbidity variables and survival duration at the time of AD diagnosis. Clinicians will find the data useful as they consider prognoses for their patients, which can inform goals of care.
  • Not discussed was whether treatment of potentially reversible conditions was withheld or modified due to severity of dementia, which could clearly impact survival.
  • Other areas of potential interest not covered in this study include psychosocial variables such as economic status, access to resources, presence of a caregiver, and urban vs. suburban dwelling.
  • Important to note is that this study studies survival after AD diagnosis, which is not necessarily the same as survival after onset of disease.
Funding Source and Role: 
National Institute on Aging. No role in design, conduct, or reporting or the decision to submit the manuscript
Created By: 
Lesley Wiesenfeld, MD, Mt. Sinai Hospital, University of Toronto, Toronto, Canada
This is a review of the validity of a single study; the ‘bottom lines’ do not reflect comparison with the rest of the literature on this subject.