Patients diagnosed with atypical types of Alzheimer’s disease may have shorter survival compared with those who have the typical type of the condition, a large retrospective study found.
Investigators analyzed 2,081 patients with biomarker-confirmed Alzheimer’s disease who visited a memory clinic between 1998 and 2023. They compared the patients with typical symptoms—such as memory loss—with those presenting with less common features like visual processing problems, language deficits, or behavioral changes.
These atypical phenotypes included posterior cortical atrophy (PCA), logopenic variant primary progressive aphasia (lvPPA), and behavioral variant Alzheimer’s disease (bvAD).
The median survival among patients with atypical Alzheimer’s disease was 6.3 years, nearly 1 year shorter compared with the 7.2 years observed in typical cases.
“Patients with atypical [Alzheimer's disease] remained at 31% higher risk of mortality than patients with typical [Alzheimer's disease] (hazard ratio = 1.31 [1.10–1.56], P = .002),” said lead study author Ilse Bader, of Amsterdam Neuroscience in the Neurodegeneration program in the Netherlands, and colleagues.
The investigators adjusted for known mortality risk factors, including age, sex, education, APOEε4 genotype, and cognitive function as measured by the Mini-Mental State Examination (MMSE).
Among atypical subtypes, median survival estimates were:
PCA: 6.3 years
lvPPA: 6.6 years
bvAD: 6.3 years.
Differences among these subtypes were not statistically significant, likely as a result of smaller sample sizes.
Using Cox proportional hazards models, the investigators found that atypical presentations were independently associated with higher mortality risk. PCA, specifically, was linked to a 35% increased risk of mortality compared with typical Alzheimer’s disease.
Additional findings showed that older age, male sex, and lower MMSE scores were associated with greater mortality. Conversely, patients with one copy of the APOEε4 gene had a lower risk of mortality compared with noncarriers.
Alzheimer’s disease pathology was confirmed in all participants using either cerebrospinal fluid analysis or positron emission tomography imaging. The investigators excluded patients with known genetic variants of Alzheimer’s disease or non–Alzheimer's disease dementia diagnoses.
Mortality data were obtained from a national registry. The average follow-up time was 5.4 years, with some patients followed for up to 18 years.
Although differences in survival were modest, the investigators noted that atypical cases often occur at younger ages and may be harder to identify, potentially delaying diagnosis and affecting care strategies.
The findings suggested that clinical phenotypes may be an independent predictor of survival and could inform patient counseling and care planning.
Full disclosures are available in the original study.
Source: Neurology
