Journal of Alzheimer's Disease - Volume 50, issue 1

Authors: Carmona-Iragui, María | Fernández-Arcos, Ana | Alcolea, Daniel | Piazza, Fabrizio | Morenas-Rodriguez, Estrella | Antón-Aguirre, Sofía | Sala, Isabel | Clarimon, Jordi | Dols-Icardo, Oriol | Camacho, Valle | Sampedro, Frederic | Munuera, Josep | Nuñez-Marin, Fidel | Lleó, Alberto | Fortea, Juan | Gómez-Ansón, Beatriz | Blesa, Rafael

Article Type: Short Communication

Abstract: We report a biomarker and genetic evaluation of four patients with cerebral amyloid angiopathy-related inflammation (CAA-ri) treated with corticosteroids. Patients presented with focal symptomatology and cognitive impairment. MRI revealed cortical microbleeds and asymmetrical hyperintense white matter lesions (WML). Cerebrospinal fluid (CSF) biomarker analyses showed increased anti-Aβ autoantibodies, t-Tau, and p-Tau and decreased Aβ40 and Aβ42 . After treatment, focal symptomatology disappeared, and WML and anti-Aβ autoantibodies decreased. The APOE ɛ 4 allele was overrepresented. Florbetapir-PET showed cortical deposition with lower retention in swollen areas. In the case of suspected CAA-ri, both CSF anti-Aβ autoantibodies levels and Florbetapir-PET could …provide highly useful data to guide the correct diagnosis. Show more

Keywords: Biomarkers, cerebral amyloid angiopathy, cerebrospinal fluid, Florbetapir-PET, inflammation

DOI: 10.3233/JAD-150614

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 1-7, 2016

Authors: Charidimou, Andreas

Article Type: Research Article

Abstract: Cerebral amyloid angiopathy– related inflammation (CAA-ri) is an aggressive disease subtype of CAA with characteristic clinical and radiological findings. CAA-ri is an important diagnosis to reach in clinical practice, as patients typically respond to prompt immunosuppressive treatment. A definitive diagnosis of CAA-ri still requires a brain biopsy, and hence developing non-invasive diagnostic criteria and biomarkers for this syndrome are key priorities in the field. CAA-ri has gained additional interest for its notable similarities to amyloid-related imaging abnormalities, a complication of immunotherapy treatments in Alzheimer’s disease patients. In this commentary, the current state of biomarkers research for CAA-ri and recently suggested …diagnostic criteria are put into context. Show more

Keywords: Alzheimer’s disease, amyloid-related imaging abnormalities (ARIA), cerebral amyloid angiopathy, cerebral microbleeds, cerebrospinal fluid biomarker

DOI: 10.3233/JAD-151042

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 9-11, 2016

Authors: Gao, Lei | Cui, Zhen | Shen, Liang | Ji, Hong-Fang

Article Type: Short Communication

Abstract: Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are two major health issues, and increasing evidence in recent years supports the close connection between these two diseases. The present study aimed to explore the shared genetic etiology underlying T2D and AD based on the available genome wide association studies (GWAS) data collected through August 2014. We performed bioinformatics analyses based on GWAS data of T2D and AD on single nucleotide polymorphisms (SNPs), gene, and pathway levels, respectively. Six SNPs (rs111789331, rs12721046, rs12721051, rs4420638, rs56131196, and rs66626994) were identified for the first time to be shared genetic factors between T2D and …AD. Further functional enrichment analysis found lipid metabolism related pathways to be common between these two disorders. The findings may have important implications for future mechanistic and interventional studies for T2D and AD. Show more

Keywords: Alzheimer’s disease, bioinformatics, genetic basis, genome wide association studies, SNPs, type 2 diabetes

DOI: 10.3233/JAD-150580

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 13-17, 2016

Authors: Sacco, Guillaume | Caillaud, Corinne | Ben Sadoun, Gregory | Robert, Philippe | David, Renaud | Brisswalter, Jeanick

Article Type: Research Article

Abstract: Background: Epidemiological studies highlight the relevance of regular exercise interventions to enhance or maintain neurocognitive function in subjects with cognitive impairments. Objectives: The aim of this study was to ascertain the effect of aerobic exercise associated with cognitive enrichment on cognitive performance in subjects with mild cognitive impairment (MCI). Method: Eight participants with MCI (72 ± 2 years) were enrolled in a 9-month study that consisted of two 3-months experimental interventions separated by a training cessation period of 3 months. The interventions included either aerobic exercise alone or aerobic exercise combined with cognitive enrichment. The exercise …program involved two 20-min cycling exercise bouts per week at an intensity corresponding to 60% of the heart rate reserve. Cognitive performance was assessed using a task of single reaction time (SRT) and an inhibition task (Go-no-Go) before, immediately after, and 1 month after each intervention. Results: The exercise intervention improved the speed of responses during the Go-no-Go task without any increase in errors. This improvement was enhanced by cognitive enrichment (6 ± 1% ; p  >  0.05), when compared with exercise alone (4 ± 0.5% ,). Following exercise cessation, this positive effect disappeared. No effect was observed on SRT performance. Conclusion: Regular aerobic exercise improved cognitive performance in MCI subjects and the addition of cognitive tasks during exercise potentiated this effect. However, the influence of aerobic exercise on cognitive performance did not persist after cessation of training. Studies involving a larger number of subjects are necessary to confirm these results. Show more

Keywords: Alzheimer’s disease, cognition, interaction between physiological and cognitive process

DOI: 10.3233/JAD-150194

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 19-25, 2016

Authors: Lim, Shir Lynn | Gao, Qi | Nyunt, Ma Shwe Zin | Gong, Lingli | Lunaria, Josephine B. | Lim, May Li | Ling, Audrey | Lam, Carolyn Su-Ping | Richards, Arthur Mark | Ling, Lieng Hsi | Ng, Tze Pin

Article Type: Research Article

Abstract: Background: Few studies have comprehensively evaluated the relationship between vascular disease and cognition of older adults without cardiac disease. Objective: We explored the associations of structural atherosclerosis, vascular stiffness, and reactivity with global, memory, attention, language, visuospatial ability, and executive function in community-dwelling, non-demented older Asians without cardiac diseases. Methods: Cognition was assessed by Mini-Mental State Examination (MMSE) (n  = 308) and detailed neuropsychological tests (n  = 155). Vascular measures included carotid intima-media thickness; aortic stiffness [carotid-femoral pulse wave velocity (CFPWV), aortic augmentation index (AI), and aortic pulse pressure (PP)]; carotid stiffness [elasticity modulus (Ep), beta index (β), …arterial compliance (AC), carotid AI]; and endothelial function [reactive hyperemia index (RHI)]. Multivariable analyses controlled for potential confounding by demographics, apolipoprotein E genotype and cardiovascular risk factors. Results: The participants’ mean age was 63.0 ± 6.1 years. Inverse associations with MMSE were found for AC (β= 0.128, p  = 0.019), Ep (β= –0.151, p  = 0.008), β index (β= –0.122, p  = 0.029), carotid stiffness z-score (β= –0.154, p  = 0.007); with executive function for CFPWV (β= –0.209, p  = 0.026), AC (β= 0.214, p  = 0.005), Ep (β= –0.160, p  = 0.050), β index (β= –0.165, p  = 0.041), and both aortic (β= –0.229, p  = 0.010) and carotid (β= –0.208, p  = 0.010) stiffness z-scores; with verbal memory for AI (β= –0.229, p  = 0.004) and aortic (β= –0.263, p  = 0.004) stiffness z-score; with language for AI (β= –0.155, p  = 0.025), aortic stiffness z-score (β= –0.196, p  = 0.011). RHI positively correlated with visuospatial ability (β= 0.195, p  = 0.013) and executive function (β= 0.151, p  = 0.045). Conclusion: The results support a link between systemic vascular health and neurocognitive function in older Asian adults. Subclinical noninvasive measures of arterial stiffness and reactivity may identify individuals vulnerable to cognitive impairment. Show more

Keywords: Arterial stiffness, carotid intima-media thickness, cognition, endothelial function

DOI: 10.3233/JAD-150516

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 27-40, 2016

Authors: Lebowitz, Brian K. | Weinstein, Cheryl | Beiser, Alexa | Seshadri, Sudha | Wolf, Philip A. | Auerbach, Sandford | Au, Rhoda

Article Type: Research Article

Abstract: Although neuropsychological tests are commonly used in the evaluation of possible mild cognitive impairment (MCI), poor test scores may be indicative of factors other than neurological compromise. The current study assessed the role of lifelong reading disorder on MCI classification. Community dwelling older adults with a suspected developmental reading disorder were identified by inference based on reading test performance. Individuals with a suspected reading disorder were significantly more likely to perform at a level consistent with MCI on several commonly used neuropsychological tests. The findings suggest a relationship between a history of reading disorder and MCI classification.

Keywords: Alzheimer’s disease, cognition, dyslexia, learning disorders, memory disorders, mild cognitive impairment, neuropsychological tests

DOI: 10.3233/JAD-150543

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 41-45, 2016

Authors: Michalowsky, Bernhard | Thyrian, Jochen René | Eichler, Tilly | Hertel, Johannes | Wucherer, Diana | Flessa, Steffen | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: The majority of people with dementia (PwD) live at home and require professional formal care and informal care that is generally provided by close relatives. Objective: To determine the utilization and costs of formal and informal care for PwD, indirect costs because of productivity losses of caregivers, and the associations between cost, socio-demographic and clinical variables. Methods: The analysis includes the data of 262 community-dwelling PwD and their caregivers. Socio-demographics, clinical variables, and the utilization of formal care were assessed within the baseline assessment. To evaluate informal care costs, the Resource Utilization in Dementia (RUD) …questionnaire was used. Costs were calculated from a social perspective. Associations were evaluated using multiple linear and logistic regression models. Results: Formal care services were utilized less (26.3%) than informal care (85.1%), resulting in a cost ratio of one to ten(1,646 €; 16,473 €, respectively). In total, 29% of caregivers were employed, and every seventh (14.3%) experienced productivity losses, which corresponded to 1,258 € annually. Whereas increasing deficits in daily living activities were associated with higher formal and higher informal costs, living alone was significantly associated with higher formal care costs and the employment of a caregiver was associated with lower informal care costs. Conclusion: Informal care contributes the most to total care costs. Living alone is a major cost driver for formal costs because of the lower availability of potential informal care. The availability of informal care is limited and productivity losses are increased when a caregiver is employed. Show more

Keywords: Alzheimer’s disease, caregivers, cost of illness, dementia, economics, health resources, patient care

DOI: 10.3233/JAD-150600

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 47-59, 2016

Authors: Marra, Camillo | Gainotti, Guido | Fadda, Lucia | Perri, Roberta | Lacidogna, Giordano | Scaricamazza, Eugenia | Piccininni, Chiara | Quaranta, Davide

Article Type: Research Article

Abstract: Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer’s disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each …memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia. Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, conversion, integration of memory scores, neuropsychological markers, Rey-Osterrieth Complex Figure delayed reproduction, verbal immediate and delayed recall

DOI: 10.3233/JAD-150613

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 61-70, 2016

Authors: Steenland, Kyle | Goldstein, Felicia C. | Levey, Allan | Wharton, Whitney

Article Type: Research Article

Abstract: Background: Several studies have shown higher Alzheimer’s disease (AD) incidence rates are in African-Americans (AAs) than Caucasians (CCs). If this finding is consistent across studies, it raises important etiologic questions regarding factors responsible for this discrepancy. It also affects the likely public health burden of AD in the US in the future, as the non-Caucasian population becomes the majority. Objective: Estimate the AA/CC rate ratio for AD incidence across all available studies. Methods: We conducted a meta-analysis of population-based studies for the rate ratio (RR) of AD incidence for AAs versus CCs, after identifying six relevant …studies from the literature. We calculated an AA/CC rate ratio across all studies using inverse-variance weighting, and assessed inter-study heterogeneity. Using these incidence data, as well as data on survival after diagnosis, and on all-cause mortality, we also estimated the US prevalence of AD among AAs and CCs. Results: There were six population-based studies with data comparing AD incidence between AAs and CCs, with an estimated 370 AA and 640 CC incident cases. The meta-analysis RR showed that the AD rate for AAs was 64% higher than for CCs (RR = 1.64 (95% CI 1.35-2.00)) 1.35-2.00)), with no evidence of heterogeneity. We estimated the current US AD prevalence for ages 65–90 to be 5.5% for CCs, and 8.6% for AAs (prevalence ratio 1.56). Conclusion: AAs have an increased risk of incident and prevalent AD compared to CCs for reasons which are unknown, but are hypothesized to reflect biological, psychological, and socioeconomic factors. Show more

Keywords: African-American, Alzheimer’s disease, Caucasian, incidence, prevalence, race

DOI: 10.3233/JAD-150778

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 71-76, 2016

Authors: Bolós, Marta | Llorens-Martín, María | Jurado-Arjona, Jerónimo | Hernández, Félix | Rábano, Alberto | Avila, Jesús

Article Type: Research Article

Abstract: The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of tauopathies. Excess tau can be released into the extracellular medium in a physiological or pathological manner to be internalized by surrounding neurons—a process that contributes to the spread of this protein throughout the brain. Such spreading may correlate with the progression of the abovementioned diseases. In addition to neurons, tau can be internalized into other cells. Here we demonstrate that microglia take up tau in vitro and in vivo . In this regard, microglia from primary cultures internalized soluble (human recombinant tau42) and insoluble (homogenates derived from …human AD brain) tau in vitro. Furthermore, using stereotaxic injection of tau in mice in vivo , we show that murine microglia internalize human tau. In addition, we demonstrate, for the first time, that microglia colocalize with various forms of tau in postmortem brain tissue of patients with Alzheimer’s disease and non-demented control subjects. Our data reveal a potential role of microglia in the internalization of tau that might be relevant for the design of strategies to enhance the clearance of extracellular tau in neurodegenerative diseases characterized by the accumulation of this protein. Show more

Keywords: Alzheimer’s disease, clearance, microglia, tau protein, tauopathies

DOI: 10.3233/JAD-150704

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 77-87, 2016