Factors Determining Disease Duration in Alzheimer’s Disease: A Postmortem Study of 103 Cases Using the Kaplan-Meier Estimator and Cox Regression

Abstract

Factors associated with duration of dementia in a consecutive series of 103 Alzheimer's disease (AD) cases were studied using the Kaplan-Meier estimator and Cox regression analysis (proportional hazard model). Mean disease duration was 7.1 years (range: 6 weeks–30 years, standard deviation = 5.18); 25% of cases died within four years, 50% within 6.9 years, and 75% within 10 years. Familial AD cases (FAD) had a longer duration than sporadic cases (SAD), especially cases linked to presenilin (PSEN) genes. No significant differences in duration were associated with age, sex, or apolipoprotein E (Apo E) genotype. Duration was reduced in cases with arterial hypertension. Cox regression analysis suggested longer duration was associated with an earlier disease onset and increased senile plaque (SP) and neurofibrillary tangle (NFT) pathology in the orbital gyrus (OrG), CA1 sector of the hippocampus, and nucleus basalis of Meynert (NBM). The data suggest shorter disease duration in SAD and in cases with hypertensive comorbidity. In addition, degree of neuropathology did not influence survival, but spread of SP/NFT pathology into the frontal lobe, hippocampus, and basal forebrain was associated with longer disease duration.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy: effects of genetic, demographic and neuropathological variables

“…Mean survival of the 84 FTLD-TDP cases was 7.9 years, similar to the 7.1 years recorded in a recent study of 102 AD cases [5], but longer than the 5.2 years and 6.5 years in AD estimated by Doody et al [26] and Feldman et al [27] respectively. Mean survival was also greater than the 6.08 years reported for a large sample of pre-senile dementia cases in the north of England, UK, but which comprised largely AD and vascular dementia (VD) [36].…”

“…In addition, the data suggested that survival was similar in familial and sporadic FTLD-TDP. This result contrasts with AD in which familial cases in general and cases specifically linked to presenilin 1 (PSEN1) mutation exhibited increased survival [5].…”

“…In typical applications, the cases can also be grouped according to a categorical predictor variable and the effect of the variable on survival tested. Where two groups were present, e.g., familial/sporadic, male/female, presence/absence of co-morbidity, survival was compared using the log-rank test which determines whether the hazard ratio (HR) is significantly different from unity [5].…”

“…In each of these analyses, variables were modeled individually and were corrected for gender and age. Statistical significance in these tests was based on t and the Wald statistic [5].…”

“…Hence, survival may depend on age at diagnosis, sex, disease subtype, and severity of progression [5]. The objective of the present study was to investigate the influence of genetics, demographic variables, co-morbidity, and neuropathology on survival, as measured by duration of dementia, in a sample of well-documented FTLD-TDP cases [10].…”