Predictors of long-term cognitive outcome in Alzheimer's disease

Abstract

IntroductionThe objective of this study was to describe the longitudinal cognitive outcome in Alzheimer's disease (AD) and analyze factors that affect the outcome, including the impact of different cholinesterase inhibitors (ChEI).MethodsIn an open, three-year, nonrandomized, prospective, multicenter study, 843 patients were treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every six months, patients were assessed using several rating scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the dose of ChEI was recorded. Sociodemographic and clinical characteristics were investigated. The relationships of these predictors with longitudinal cognitive ability were analyzed using mixed-effects models.ResultsSlower long-term cognitive decline was associated with a higher cognitive ability at baseline or a lower level of education. The improvement in cognitive response after six months of ChEI therapy and a more positive longitudinal outcome were related to a higher mean dose of ChEI, nonsteroidal anti-inflammatory drug (NSAID)/acetylsalicylic acid usage, male gender, older age, and absence of the apolipoprotein E (APOE) ε4 allele. More severe cognitive impairment at baseline also predicted an improved response to ChEI treatment after six months. The type of ChEI agent did not influence the short-term response or the long-term outcome.ConclusionsIn this three-year AD study performed in a routine clinical practice, the response to ChEI treatment and longitudinal cognitive outcome were better in males, older individuals, non-carriers of the APOE ε4 allele, patients treated with NSAIDs/acetylsalicylic acid, and those receiving a higher dose of ChEI, regardless of the drug agent.

Risk Factors That Affect Life Expectancy in Alzheimer's Disease: A 15-Year Follow-Up

“…Therefore, it is assumed that those individuals require a relatively larger burden of AD pathology at the onset of clinical symptoms [30]. The brain-reserve hypothesis is supported by the observation of faster cognitive decline among patients with more years of education in several [19,29,31] but not all [32,33] studies. Nevertheless, most previous studies have demonstrated that the participants' level of education does not influence survival time after the onset or diagnosis of AD [6,10,13,31].…”

“…Participation in studies and variations in mortality may be more influenced by other factors among the oldest patients, such as manifestation of the disease, concomitant medical disorders, and psychiatric symptoms. Nevertheless, a recent study from our group showed a better cognitive response to ChEI therapy and a slower disease progression among older individuals with AD [19]. The oldest individuals might have a reduced cognitive reserve because of their advanced age that can lead to an earlier manifestation of the typical AD symptoms, worse performance on standardized cognitive tests, and hence earlier detection of the disease.…”

“…However, APOE genotype did not affect the length of life after diagnosis. Some studies found that the presence of at least one APOE ε4 allele implied an earlier onset [36] and a faster rate of cognitive deterioration [19,37]. However, other authors reported no difference in the onset of AD [38] and progression rate between ε4 carriers and noncarriers [38,39], or a faster cognitive decline in noncarriers [40].…”

“…The SATS is a prospective, open-label, observational, nonrandomized, multicenter study that has been described in several publications [18,19,20,21]. In total, 1,258 participants were recruited until April 2008 by 14 memory clinics that cover different parts of Sweden.…”

Gender-Dependent Levels of Hyaluronic Acid in Cerebrospinal Fluid of Patients with Neurodegenerative Dementia

“…Whether the gender differences are due to the fact that women live longer than men, is still a subject of debate, however several meta-studies have shown that women indeed have an increased risk of developing AD (19)(20)(21). Moreover, there are two studies showing that men with AD respond better to cholinesterase inhibitors treatment than women (22,23). Dementia with Lewy bodies, on the other hand, is a male-dominant disease (2), which further indicates that the mechanisms underlying these two neurodegenerative diseases differ.…”