Journal of Alzheimer's Disease - Volume 65, issue 3

Authors: Baker, Jenalle E. | Lim, Yen Ying | Jaeger, Judith | Ames, David | Lautenschlager, Nicola T. | Robertson, Joanne | Pietrzak, Robert H. | Snyder, Peter J. | Villemagne, Victor L. | Rowe, Christopher C. | Masters, Colin L. | Maruff, Paul

Article Type: Research Article

Abstract: Recent meta-analyses suggest that episodic memory impairment associated with preclinical Alzheimer’s disease (AD) equates to 0.15–0.24 standard deviations below that of cognitively healthy older adults. The current study aimed to characterize impairments in verbal acquisition and recall detectable at a single assessment, and investigate how verbal learning and episodic memory deteriorates in preclinical AD. A verbal list-learning task, the International Shopping List Test (ISLT), was administered multiple times over an 18-month period, to three groups of participants: amyloid-beta negative healthy older adults (Aβ – CN; n  = 50); Aβ + positive healthy older adults (preclinical AD; n  = 25); and Aβ + …positive individuals diagnosed with mild cognitive impairment (prodromal AD; n  = 22). At baseline, there was no significant difference between the preclinical AD and control groups rate of acquisition, or total and delayed recall, however all indices were impaired in prodromal AD. Performance on ISLT total score improved in the control group over the 18-month period, but showed a moderate magnitude decline in the preclinical AD group (Cohen’s d  = – 0.63, [– 1.12, – 0.14]) and the prodromal AD group (Cohen’s d  = – 0.36, [– 0.94, 0.22]). No significant impairment in acquisition associated with preclinical AD was seen at baseline. Individuals with preclinical AD showed a significantly different performance on the ISLT total score over an 18-month period, compared to those without abnormal Aβ . Individuals with prodromal AD showed substantial impairment on the ISLT at baseline and declined to a greater extent over time. Show more

Keywords: Alzheimer’s disease, amyloid-β protein, cognitive decline, learning curve, memory and learning tests, mild cognitive impairment, neuropsychology, transfer of learning

DOI: 10.3233/JAD-180344

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 977-988, 2018

Authors: Lozupone, Madia | Panza, Francesco | Piccininni, Marco | Copetti, Massimiliano | Sardone, Rodolfo | Imbimbo, Bruno P. | Stella, Eleonora | D’Urso, Francesca | Barulli, Maria Rosaria | Battista, Petronilla | Grasso, Alessandra | Tortelli, Rosanna | Capozzo, Rosa | Coppola, Francesco | Abbrescia, Daniela Isabel | Bellomo, Antonello | Giannelli, Gianluigi | Quaranta, Nicola | Seripa, Davide | Logroscino, Giancarlo

Article Type: Research Article

Abstract: Background: Most studies focused on only one measure of social dysfunction in older age, without proper validation and distinction across different dimensions including subjectivity, structural, and functional aspects. Objective: We sought to validate the Social Dysfunction Rating Scale (SDRS) and its factorial structure, also determining the association of SDRS with cognitive functions, global psychopathology, and social deprivation. Methods: The SDRS was administered to 484 Italian community-dwelling elderly, recruited in the GreatAGE study, a population-based study on aging conducted in Castellana Grotte, Bari, Southern Italy. We determined objective and subjective psychometric properties of SDRS against the gold …standard evaluation of social dysfunction according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders (SCID-I) criterion. Results: The SDRS showed a moderate accuracy with an optimal cut-off of 26 maximized with higher sensitivity (0.74,95% CI:0.63–0.84) than specificity (0.57,95% CI:0.50–0.64). A five-factor structure was carried out and five dimensions of SDRS were identified (loneliness; social isolation; feeling of contribution/uselessness; lack of leisure activities; anxiety for the health). Education and global cognitive functions were inversely correlated to SDRS, while a direct association with global psychopathology, depression, and apathy was found. The prevalence of higher SDRS scores was major in subjects with current psychiatric disorders versus other subjects.∥Conclusion : The SDRS could be a valid instrument to capture both size and quality of social dysfunction, both in subjects with psychiatric disorders and in normal subjects. Several categories of social dysfunction differed only in the degree of health deprivation, not in social or material deprivation. Show more

Keywords: Cognitive function, deprivation, lifestyle, loneliness, old age, social dysfunction

DOI: 10.3233/JAD-180466

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 989-1000, 2018

Authors: Sun, Minghao | Zhao, Yinghui | Han, Men | Zhang, Baozhu | Zhang, Xiao | Zhang, Qichao | Lim, Nastasia K.-H. | Wang, Wen-An | Huang, Fu-De

Article Type: Research Article

Abstract: Neuronal amyloid-β (Aβ) accumulation plays an important role in the pathogenesis of Alzheimer’s disease (AD). The conformation and toxicity of Aβ are regulated by lipids on the plasma membrane. Previously, we found downregulation of Rolling Blackout (RBO) or phosphatidylinositol-4-kinase type IIIα (PI4KIIIα ) reduces neuronal Aβ accumulation and associated neural deficits in a Drosophila model expressing Aβ42 . In mammals, the homologs of RBO and PI4KIIIα were reported to form a plasma membrane-localized complex with a scaffold protein TTC7 and cytosolic protein Hyccin/FAM126A to tightly control the plasmalemmal level of phosphatidylinositol-4-phosphate. Here, we show genetic downregulation of …Drosophila TTC7 and Hyccin also reduces neuronal Aβ accumulation and associated synaptic and motor defects as well as premature death in Aβ42 -expressing flies, while overexpression of TTC7 and Hyccin produced the opposite effect. These results, together with our previous study, demonstrate that RBO/TTC7/PI4KIIIα /Hyccin regulate neuronal Aβ accumulation and associated neural deficits in the Drosophila model, further supporting the RBO/Efr3-PI4KIIIα complex as a potential therapeutic target for AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, Drosophila , Hyccin, PI4KIIIα , TTC7

DOI: 10.3233/JAD-170907

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1001-1010, 2018

Authors: Rahman-Filipiak, Annalise M. | Giordani, Bruno | Heidebrink, Judith | Bhaumik, Arijit | Hampstead, Benjamin M.

Article Type: Research Article

Abstract: Background: Subjective memory complaints (SMCs) are incorporated into the diagnosis of mild cognitive impairment (MCI) and neurodegenerative dementias; however, the relative frequency of SMCs in cognitively intact older adults and those with different types of dementia is poorly understood. Similarly, the concordance between self- versus informant-reported SMCs has not been compared across different diagnostic groups. Objective: This study aimed to evaluate the frequency of self-reported (Objective 1) and informant-reported (Objective 2) SMCs in cognitively intact adults or those diagnosed with MCI or a neurodegenerative dementia. Agreement between participant and informant complaints was also evaluated (Objective 3). …Methods: Baseline evaluation data were drawn from 488 participants (M age  = 70.49 years; M edu  = 15.62 years) diagnosed as cognitively intact, non-amnestic MCI, amnestic single domain MCI, amnestic multi-domain MCI, possible/probable Alzheimer’s disease, dementia with Lewy bodies, or frontotemporal dementia. Participants and their informants completed the Memory Assessment Clinic Questionnaire. Results: One-way ANCOVAs controlling for age, education, and depression revealed no group differences in severity of self-reported SMCs. In contrast, informant memory ratings followed the expected clinical pattern, with comparable and most impaired ratings given to participants with any dementia diagnosis, followed by those with any MCI diagnosis, followed by cognitively intact participants. There was inconsistent agreement between self- and informant-reported SMC ratings in any of the impaired groups. Conclusions: Given greater diagnostic specificity and internal consistency of informant report, clinicians should weigh this information more heavily than self-report in the diagnostic process. Show more

DOI: 10.3233/JAD-180083

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1011-1027, 2018

Authors: Scheltens, Nienke M.E. | Tijms, Betty M. | Heymans, Martijn W. | Rabinovici, Gil D. | Cohn-Sheehy, Brendan I. | Miller, Bruce L. | Kramer, Joel H. | Wolfsgruber, Steffen | Wagner, Michael | Kornhuber, Johannes | Peters, Oliver | Scheltens, Philip | van der Flier, Wiesje M. | Amsterdam Dementia Cohort, Alzheimer’s Disease Neuroimaging Initiative, German Dementia Competence Network, University of San Francisco Memory and Aging Center

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n  = 290), Alzheimer’s Disease Neuroimaging Initiative (n  = 268), Dementia Competence Network (n  = 226), and University of California, San Francisco (n  = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n  = 663) and one with most prominent non-memory impairment (n  = 403). We examined associations between cognitive subtype …and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p  < 0.001; CDR sob 4.1±0.1; p  < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (–2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE – 1.9±0.1; pinteraction <0.001; CDR sob 1.3±0.1; pinteraction <0.001). Furthermore, the non-memory subtype was associated with an increased risk of mortality compared with the memory subtype at trend level (HR = 1.36, CI = 1.00–1.85, p  = 0.05). Conclusions: AD patients with most prominently non-memory impairment show faster disease progression and higher risk of mortality than patients with most prominently memory impairment. Show more

Keywords: Alzheimer’s disease, clustering, cognition, dementia, disease progression, mortality, phenotypes, subtypes

DOI: 10.3233/JAD-171088

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1029-1039, 2018

Authors: Sutin, Angelina R. | Stephan, Yannick | Terracciano, Antonio

Article Type: Research Article

Abstract: Depressive symptoms and a history of mental disorders are associated with increased risk for dementia. Less is known about whether other aspects of psychological distress and negative self-beliefs also increase risk. The purpose of this research is to examine 1) whether eight aspects of psychological distress and self-beliefs (anxiety, negative affect, hostility, anger-in, anger-out, hopelessness, pessimism, perceived constraints) are associated with risk of incident dementia and cognitive impairment not dementia (CIND), 2) whether the associations are independent of depressive symptoms and history of a mental health diagnosis, and 3) whether the associations are also independent of behavioral, clinical, and genetic …risk factors. A total of 9,913 participants (60% female) from the Health and Retirement Study completed the baseline measures, scored in the non-impaired range of cognition at baseline, and had cognitive status assessed across the 6–8-year follow-up. Baseline measures included eight aspects of psychological distress and self-beliefs, cognitive performance, depressive symptoms, and genetic, clinical, and behavioral risk factors. Participants who scored higher on anxiety, negative affect, hostility, pessimism, hopelessness, and perceived constraints were at a 20–30% increased risk of dementia and a 10–20% increased risk of CIND. The associations held controlling for baseline depressive symptoms, history of a mental health diagnosis, clinical and behavioral risk factors, and genetic risk. Anger-in and anger-out were unrelated to risk of either dementia or CIND. Independent of the core experience of depressed affect, other aspects of negative emotionality and self-beliefs increase risk of mild and severe cognitive impairment, which suggests additional targets of intervention. Show more

Keywords: Alzheimer’s disease, dementia, psychological distress, self-beliefs

DOI: 10.3233/JAD-180119

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1041-1050, 2018

Authors: Li, Bingyu

Article Type: Book Review

DOI: 10.3233/JAD-180762

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1051-1051, 2018

Authors: Ekblad, Laura L. | Toppala, Sini | Johansson, Jouni K. | Koskinen, Seppo | Sundvall, Jouko | Rinne, Juha O. | Puukka, Pauli | Viitanen, Matti | Jula, Antti

Article Type: Correction

DOI: 10.3233/JAD-189008

Citation: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 1053-1054, 2018