Journal of Alzheimer's Disease - Volume 83, issue 3

Authors: Wang, Hualong | Xu, Ying | Ren, Rujing | Yao, Feng | Chen, Mei | Sheng, Zhihua | Guo, Xin | Li, Yan | Chen, Shengdi | Wang, Gang

Article Type: Research Article

Abstract: Background: Previous studies revealed that abnormal blood pressure (BP) plays an important role in the pathogenesis of Alzheimer’s disease (AD). However, little is known about the ambulatory BP characteristics of AD in the mild or severe stage. Objective: We explored the ambulatory BP characteristics of AD in the mild or severe stage. Methods: In the present study, 106 AD patients (42.5%male, average age 81.6 years) were enrolled from three centers in China. Clinal BP measurements at the supine and standing positions, neurological evaluations, and the 24 h ambulatory BP monitoring were performed. Results: In the …106 AD patients, 49.2%, 36.8%, and 70%of patients had 24 h, daytime, and nighttime systolic hypertension, respectively, while 19.8%, 29.2%, and 5.7%had 24 h, daytime, and nighttime diastolic hypotension. The prevalence of the reduced and reverse dipping pattern was 34.0%and 48.1%for systolic BP and 32.1%and 45.3%for diastolic BP, respectively. The daytime diastolic BP was significantly correlated with cognitive performance. After adjustment for age, sex, and body mass index, only daytime diastolic BP was associated with remarkable cognitive deterioration (p ≤0.008). Further, AD patients in the severe stage had significantly lower levels of the 24 h, daytime, and nighttime diastolic BP, compared with those in the mild stage. Conclusion: In general, AD patients were featured with high nighttime systolic BP, low daytime diastolic BP, and abnormal circadian BP rhythm of reduced and reverse dipping. The diastolic BP, especially daytime diastolic BP, was adversely correlated with the cognitive deterioration in AD. Show more

Keywords: Alzheimer’s disease, ambulatory blood pressure, blood pressure variability, dipping

DOI: 10.3233/JAD-210679

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1333-1339, 2021

Authors: Zangrossi, Andrea | Montemurro, Sonia | Altoè, Gianmarco | Mondini, Sara

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) patients show heterogeneous cognitive profiles which suggest the existence of cognitive subgroups. A deeper comprehension of this heterogeneity could contribute to move toward a precision medicine perspective. Objective: In this study, we aimed 1) to investigate AD cognitive heterogeneity as a product of the combination of within- (factors) and between-patients (sub-phenotypes) components, and 2) to promote its assessment in clinical practice by defining a small set of critical tests for this purpose. Methods: We performed factor mixture analysis (FMA) on neurocognitive assessment results of N = 230 patients with a clinical diagnosis of AD. …This technique allowed to investigate the structure of cognitive heterogeneity in this sample and to characterize the core features of cognitive sub-phenotypes. Subsequently, we performed a tests selection based on logistic regression to highlight the best tests to detect AD patients in our sample. Finally, the accuracy of the same tests in the discrimination of sub-phenotypes was evaluated. Results: FMA revealed a structure characterized by five latent factors and four groups, which were identifiable by means of a few cognitive tests and were mainly characterized by memory deficits with visuospatial difficulties (“Visuospatial AD”), typical AD cognitive pattern (“Typical AD”), less impaired memory (“Mild AD”), and language/praxis deficits with relatively spared memory (“Nonamnestic AD”). Conclusion: The structure of cognitive heterogeneity in our sample of AD patients, as studied by FMA, could be summarized by four sub-phenotypes with distinct cognitive characteristics easily identifiable in clinical practice. Clinical implications under the precision medicine framework are discussed. Show more

Keywords: Alzheimer’s disease, factor mixture analysis, heterogeneity, precision medicine

DOI: 10.3233/JAD-210719

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1341-1351, 2021

Authors: Felisberti, Fatima M.

Article Type: Research Article

Abstract: Background: Hedonic (or aesthetic) preferences to repeated sensory stimulation can remain stable over time (Island of Stability Effect, ISE) or vary with prior exposures (Mere Exposure Effect, MEE). Objective: Here we compared the liking ratings of seniors with cognitive impairments (mostly mild-to-moderate dementia, DPs) and neurotypical senior controls (CNs) to audio and visual stimuli and examined whether those ratings conformed to the ISE or the MEE predictions. Method: Participants (n  = 212) rated sets of stimuli repeated three times at weekly intervals: images of Picasso’s paintings, PANTONE color cards, and avant-garde music clips. Results: The …aggregated liking ratings of DPs and CNs were stable over time, in line with the ISE model. However, latent growth modeling indicated that those stable responses might have masked differences at the individual level, since seniors in both cohorts exhibited clusters of different responses over the time evaluated, supporting the predictions of the MEE. Notably, there was a dampening of hedonic experiences in DPs comparatively to CNs. Conclusion: The presence of hedonic responses (and individual variations) in DPs is relevant not only to their wellbeing and therapy interventions involving audio and visual stimulation, but also to the design of spaces that offset the downturn in hedonic experiences affecting seniors with cognitive impairments. Show more

Keywords: Aesthetic preferences, cognitive impairments, color, dementia, island of stability effect, mere exposure effect, music, paintings

DOI: 10.3233/JAD-210520

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1353-1366, 2021

Authors: Mommaerts, Kathleen | Willemse, Eline A.J. | Marchese, Monica | Larue, Catherine | van der Flier, Wiesje M. | Betsou, Fay | Teunissen, Charlotte E.

Article Type: Research Article

Abstract: Background: An N-terminal octapeptide cleavage of the cystatin C protein was discovered by mass spectrometry when cerebrospinal fluid (CSF) was stored at –20°C for 3 months, which did not occur when CSF was stored at –80°C. Objective: The aim was to develop an immunoassay as quality assessment tool to detect this –20°C cleavage of cystatin C in CSF and support Alzheimer’s disease research. Methods: A specific monoclonal antibody and a double indirect sandwich ELISA were developed: one assay quantifies the octapeptide uncleaved protein specifically and the other quantifies the total cystatin C present in the biological …fluid (both cleaved and uncleaved forms). The ratio of these concentrations was calculated to assess the extent of cleavage of cystatin C. The novel ELISA was validated and applied in a short-term (up to 4 weeks) and mid-term (up to one year) stability study of CSF stored at 4°C, –20°C, –80°C, and liquid nitrogen. Impact of freeze-thaw cycles, adsorption, and protease inhibitors were tested. Results: The ratio of truncated protein was modified following –20°C storage and seemed to reach a plateau after 6 months. The ratio was impacted neither by freeze-thaw cycles nor adsorption. The –20°C specific cleavage was found to be protease related. Conclusion: Using this novel double indirect sandwich ELISA, absolute levels of the total and uncleaved cystatin C and the ratio of truncated cystatin C can be measured. This assay is an easily applicable tool which can be used to confirm that CSF biospecimen are fit-for-purpose for Alzheimer’s disease research. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, cystatin C, double indirect ELISA, protein stability

DOI: 10.3233/JAD-210741

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1367-1377, 2021

Authors: Brenowitz, Willa D. | Zeki Al Hazzouri, Adina | Vittinghoff, Eric | Golden, Sherita H. | Fitzpatrick, Annette L. | Yaffe, Kristine

Article Type: Research Article

Abstract: Background: Depressive symptoms may increase risk for dementia, but findings are controversial because late-life depression may be a prodromal dementia symptom. Life course data on depression and dementia risk may clarify this association; however, data is limited. Objective: To impute adult depressive symptoms trajectories across adult life stages and estimate the association with cognitive impairment and decline. Methods: Using a pooled study of 4 prospective cohorts (ages 20–89), we imputed adult life course depressive symptoms trajectories based on Center for Epidemiologic Studies Depression Scale-10 (CESD-10) and calculated time-weighted averages for early adulthood (ages 20–49), mid-life (ages …50–69), and late-life (ages 70–89) for 6,122 older participants. Adjusted pooled logistic and mixed-effects models estimated associations of imputed depressive symptoms with two cognitive outcomes: cognitive impairment defined by established criteria and a composite cognitive score. Results: In separate models, elevated depressive symptoms in each life stage were associated with cognitive outcomes: early adulthood OR for cognitive impairment = 1.59 (95%CI: 1.35,1.87); mid-life OR = 1.94 (95%CI:1.16, 3.26); and late-life OR = 1.77 (95%CI:1.42, 2.21). When adjusted for depressive symptoms in the other life-stages, elevated depressive symptoms in early adulthood (OR = 1.73; 95%CI: 1.42,2.11) and late-life (OR = 1.43; 95%CI: 1.08,1.89) remained associated with cognitive impairment and were also associated with faster rates of cognitive decline (p  < 0.05). Conclusion: Imputing depressive symptom trajectories from pooled cohorts may help expand data across the life course. Our findings suggest early adulthood depressive symptoms may be a risk factor for cognitive impairment independent of mid- or late-life depressive symptoms. Show more

Keywords: Cognitive impairment, dementia, depression, imputation, life course

DOI: 10.3233/JAD-210588

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1379-1389, 2021

Authors: Espay, Alberto J.

Article Type: Book Review

DOI: 10.3233/JAD-215136

Citation: Journal of Alzheimer's Disease, vol. 83, no. 3, pp. 1391-1393, 2021