Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer’s disease: an 11‐year follow‐up study

Mazzeo, Salvatore; Padiglioni, Sonia; Bagnoli, Silvia; Carraro, Marco; Piaceri, Irene; Bracco, Laura; Nacmias, Benedetta; Sorbi, Sandro; Bessi, Valentina

doi:10.1111/ene.14167

Cited by 19 publications

(20 citation statements)

References 19 publications

(31 reference statements)

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“…Several studies applying multifactorial approaches found that demographic and genetic factors, such as age at onset [1,8], APOE ε4 genotype [8], and cognitive reserve [9][10][11], may influence the risk of progression from SCD to MCI and dementia.…”

Section: Introductionmentioning

confidence: 99%

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

et al. 2021

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Background Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. Methods We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. Results The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p < 0.001), and higher MAC-Q scores (p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. Conclusions Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.

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Section: Introductionmentioning

confidence: 99%

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

et al. 2021

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“…We used Cox regression analysis to ascertain that the effect of presence of IAs on progression from SCD to MCI was independent of other covariates. We considered 60 years (as suggested by Jessen et al [10] and Mazzeo et al [25]) as the cut-off value to dichotomize age at baseline. Bonferroni correction was applied to correct for multiple comparisons.…”

Section: Discussionmentioning

confidence: 99%

“…We also explored the relationship of IAs with age at baseline and APOE ε4, two well‐known risk factors for objective cognitive decline and for progression to AD in patients with SCD [25]. We found that IAs further increased the risk of progression to MCI in patients who were carriers of the APOE ɛ4 allele and in patients who were older than 60 years at baseline.…”

Section: Discussionmentioning

confidence: 99%

Huntingtin gene intermediate alleles influence the progression from subjective cognitive decline to mild cognitive impairment: A 14‐year follow‐up study

Mazzeo

Emiliani

Bagnoli

et al. 2022

Euro J of Neurology

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Background and purpose Huntingtin (HTT) is a gene containing a key region of CAG repeats. HTT alleles containing from 27 to 35 CAG repeats are termed intermediate alleles (IAs). We aimed to assess the effect of IAs on progression of cognitive impairment in patients with subjective cognitive decline (SCD). Methods We included 106 patients with SCD. All the patients underwent neuropsychological assessments and blood sample collection at baseline. Patients were followed up for a median (interquartile range) time of 13.75 (8.17) years. We genotyped APOE and HTT at the end of the follow‐up. Results Eleven out of 106 patients (10.38%, 95% confidence interval [CI] 4.57–16.18) were carriers of IAs (IA+). During the follow‐up, 44 patients (41.51%, 95% CI 32.13–50.89) progressed to mild cognitive impairment (MCI; p‐SCD group), while 62 patients (58.49%, 95% CI 49.11–67.87) did not (np‐SCD group). Rate of progression to MCI was associated with IAs, age at baseline, and APOE ɛ4. We dichotomized age at baseline (<60 years = younger patients [YP], >60 years = older patients [OP]) and then classified patients into four groups: YP/IA–, YP/IA+, OP/IA– and OP/IA+. The OP/IA+ group had a higher proportion of patients with progression from SCD to MCI (85.71%, 95% CI 59.79–100) as compared to the YP/IA– group (28.57%, 95% CI 13.60–43.54, χ2 = 15.25; p < 0.001) and the OP/IA– group (45.00%, 95% CI 32.41–57.59, χ2 = 7.903; p = 0.005). We classified patients according to APOE and IA as: ɛ4–/IA–, ɛ4–/IA+, ɛ4+/IA–, ɛ4+/IA+. The proportion of patients with progression in the ɛ4+/IA+ group (100%) was higher as compared to the ɛ4–/IA– group (33.33%, 95% CI 21.96–44.71, χ2 = 14.43; p < 0.001) and ɛ4+/IA– (55.56%, 95% CI 36.81–74.30, χ2 = 4.60; p = 0.032). Conclusions Intermediate alleles interact with age and APOE ɛ4, increasing the risk of progression to MCI in SCD patients.

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“…Previous study has identi ed that the bene cial effect of education on cognitive function can not be modi ed by the APOE ε4 status in healthy older adults with more than 4-year period follow-up [40]. In individuals with SCD, the APOE ε4 allele signi cantly increased the risk of conversion to AD dementia [41], while at the symptomatic stage, the APOE ε4 allele accelerate progression from MCI to AD dementia only in APOE ε4 carriers [32]. However, further studies will be required to understand the mechanisms underlying the role of APOE ε4 allele in regulating the effect of education on cognition across the spectrum of AD.…”

Section: Discussionmentioning

confidence: 99%

APOE ε4 Allele Modulates The Differential Effects of Education on Cognition in Alzheimer’s Continuum: The SILCODE Study

Chen

Yang

Han

2020

Preprint

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Background: Elders with subjective cognitive decline (SCD) in the absence of objective cognitive impairment are at increased risk of developing mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Previous study has reported that higher education was associated with better performance in cognitive performance in elderly people with SCD. However, it is not clear whether there is a differential effect of education on cognition between healthy controls (HC), individuals with SCD and patients with cognitive impairment (CI).Methods: We performed a cross-sectional study that included 186 HC, 279 SCD subjects and 79 patients with CI from the Sino Longitudinal Study on Cognitive Decline (SILCODE) project. A series of neuropsychological tests of memory, executive, language, and general cognitive function were used to assess the subjects cognitive performance. We performed multiple linear regression models to examine the effect of education on neuropsychological test scores in the total sample and then described differences in the effect according to three different groups. In addition, we presented the effect of education on total test score expressed as a global composite z-scores in the total sample and three different groups, respectively. Furthermore, we examined whether apolipoprotein E ε4 allele (APOE ε4) status would regulate the effect of education on the global composite score among three different groups.Results: Education has a positive effect on cognition in the total sample. Stratification for different groups showed that the positive effect of education on cognition is found in HC and SCD group, while education has a negative effect on cognition in the CI group. Furthermore, we found the APOE ε4 allele does not modify the positive effect of education on cognition in the HC group, but the APOE ε4 allele weaken that beneficial effect in the SCD group and maintain the negative effect in the CI group.Conclusions: High education may delay the progression from SCD to cognitive impairment and yield differential effects on cognition across the spectrum of AD. Furthermore, that differential effects are subjected to modulation by the APOE ε4 status.

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Assessing the effectiveness of subjective cognitive decline plus criteria in predicting the progression to Alzheimer’s disease: an 11‐year follow‐up study

Cited by 19 publications

References 19 publications

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Gender differences in cognitive reserve: implication for subjective cognitive decline in women

Huntingtin gene intermediate alleles influence the progression from subjective cognitive decline to mild cognitive impairment: A 14‐year follow‐up study

APOE ε4 Allele Modulates The Differential Effects of Education on Cognition in Alzheimer’s Continuum: The SILCODE Study

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