Journal of Alzheimer's Disease - Volume 72, issue 4

Authors: Lövheim, Hugo | Gustafsson, Maria | Isaksson, Ulf | Karlsson, Stig | Sandman, Per-Olof

Article Type: Research Article

Abstract: Background: For research purposes, there is a need for tools to assess an individual’s level of cognitive function. For survey-based investigations in nursing home contexts, proxy ratings allow the assessment also of individuals with severe cognitive impairment. Objective: The aim of this study was to describe the feasibility and psychometric properties of Gottfries’ cognitive scale when used in a nursing home context for proxy rating of cognitive function. Method: The psychometric properties of Gottfries’ cognitive scale were investigated in a sample of 8,492 nursing home residents in Västerbotten County, Sweden, using item response theory and classic …scale theory-based approaches. Results: Cognitive function could be scored in 97.1% of the assessed individuals. The scale had a negligible floor effect, it had items with a large spread in difficulties, it appeared linear, and it distributed the assessed individuals equally over the scale. Internal consistency (Cronbach’s alpha) was 0.967, and an exploratory factor analysis revealed three factors of the scale – interpreted to represent orientation to time, to place, and to person. Conclusion: Gottfries’ cognitive scale is a feasible tool for grading cognitive function among nursing home residents using staff proxy ratings. The scale has excellent psychometric properties with a very high internal consistency, a favorable distribution of item difficulties producing an almost rectangular distribution of scores, and a negligible floor effect. The scale thus can be recommended for use in survey-based investigations in nursing home contexts. Show more

Keywords: Assessment, cognitive function, cognitive impairment, dementia, measurement, nursing home, scale, survey

DOI: 10.3233/JAD-190599

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1251-1260, 2019

Authors: Choo, IL Han | Chong, Ari | Chung, Ji Yeon | Kim, Hoowon

Article Type: Research Article

Abstract: Background: Subjective memory complaints (SMC) are a risk factor for Alzheimer’s disease. Objective: We aimed to explore the association between SMC and regional amyloid-β (Aβ) deposition in mild cognitive impairment (MCI). Methods: Sixty-eight individuals with MCI were recruited. [18 F]Florbetaben PET scans were performed. T1-weighted 3D volumes were also acquired for co-registration with PET and for defining the regions of interest (ROI). Two step exploratory partial correlation analyses between SMC and Aβ deposition were performed with covariates of age, sex, education, and depression. Furthermore, for the priori ROI that had the most significant partial correlation, we …investigated the correlation between the SMC and regional Aβ burden using a multiple linear regression model controlling for depression, age, sex, and education. Results: Significant positive correlations between the SMC and Aβ burden was found in the medial temporal ROI (first step) and in the left parahippocampus ROI (second step). In the priori left parahippocampus, we found significant correlation between the SMC and Aβ burden (R2  = 0.473, p  = 0.014). Conclusions: Our study suggested that the SMC was associated with amyloid accumulation, especially in the left parahippocampus, in individuals with MCI. Show more

Keywords: Amyloid burden, mild cognitive impairment, subjective memory complaints

DOI: 10.3233/JAD-190816

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1261-1268, 2019

Authors: Ording, Anne G. | Veres, Katalin | Horváth-Puhó, Erzsébet | Glymour, M. Maria | Rørth, Mikael | Henderson, Victor W. | Sørensen, Henrik T.

Article Type: Research Article

Abstract:  Observational studies have shown inverse associations between neurological diseases, particularly dementia, and subsequent cancer risk, but is unknown whether this association is valid or arises from bias. We conducted a Danish nationwide cohort study using population-based health registries (1980–2012). The study included patients with dementia (n  = 173,434) and with Parkinson’s disease (n  = 28,835). We followed patients for 10 years to assess subsequent cancer diagnoses. We computed absolute reduction in cancer risk attributable to dementia or Parkinson’s disease (expected minus the observed number of cancer cases divided by the person time) and standardized incidence rate ratios (SIRs) as the observed to …expected number of cancers, based on sex-, age-, and calendar year-standardized national incidence rates. During 10 years, the reduction in cancer cases were 79.9 per 10,000 person-years for Alzheimer’s disease [SIR = 0.68 (95% CI: 0.66, 0.70)], 74.4 per 10,000 person-years for vascular dementia [SIR = 0.71 (95% CI: 0.67, 0.74)], 55.8 per 10,000 person-years [SIR = 0.77 (95% CI: 0.75, 0.78)] for all-cause dementia, and 4.0 per 10,000 person-years [SIR = 0.98 (95% CI: 0.95, 1.02) for Parkinson’s disease. Associations were nearly similar for solid tumors diagnosed at localized, regional, or distant stages. We found an inverse association between dementia and cancer risk, with similar associations when considering only cancers diagnosed at distant stage. The cancer risk varied by type of dementia, with a gradient toward a stronger protective effect associated with Alzheimer’s disease and vascular dementia, which may favor a biological explanation. Overall results do not show an inverse association between Parkinson’s disease and cancer. Show more

Keywords: Alzheimer’s disease, dementia, epidemiology, neoplasms, Parkinson’s disease, risk

DOI: 10.3233/JAD-190867

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1269-1277, 2019

Authors: Ułamek-Kozioł, Marzena | Czuczwar, Stanisław J. | Kocki, Janusz | Januszewski, Sławomir | Bogucki, Jacek | Bogucka-Kocka, Anna | Pluta, Ryszard

Article Type: Research Article

Abstract:  There is currently no knowledge about the expression profile of the autophagy (BECN1 ), mitophagy (BNIP3 ), and apoptosis (CASP3 ) genes in the CA3 region of the hippocampus after cerebral ischemia. In addition, it is unknown whether genes for BECN1 , BNIP3 , and CASP3 have any effect on the neuronal death in the CA3 area of the hippocampus due to ischemia. In this study, for the first time, we present, by means of a quantitative PCR protocol with reverse transcriptase, the expression of BECN1 and CASP3 genes in the neuronal CA3 region of the hippocampus …with the co-expression of the mitochondrial BNIP3 gene, which genes are associated with Alzheimer’s disease, in the ischemic model of Alzheimer’s disease in the rat. The present study showed that after ischemia, the CASP3 gene was significantly expressed within 7–30 days, the BECN1 gene was significantly overexpressed on the thirtieth day, and the BINP3 gene was lowered below control values during post-ischemic follow-up period. The caspase-dependent neuronal death in the CA3 region of the hippocampus after ischemia is not accompanied by overexpression of the BNIP3 gene. Our data may therefore suggest a new insight into the BNIP3 gene in the regulation of neuronal mitophagy in neurodegeneration in the CA3 region of the hippocampus after ischemia. This indicates no involvement of the BNIP3 gene along with the CASP3 gene in the CA3 region of the hippocampus in delayed neuronal death after brain ischemia. Show more

Keywords: Alzheimer’s disease, apoptosis, autophagy, brain ischemia, cardiac arrest, genes, mitophagy

DOI: 10.3233/JAD-190966

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1279-1286, 2019

Authors: Valech, Natalia | Sánchez-Benavides, Gonzalo | Tort-Merino, Adrià | Coll-Padrós, Nina | Olives, Jaume | León, María | Falcon, Carles | Molinuevo, José Luis | Rami, Lorena

Article Type: Research Article

Abstract: Background: Exploring the relationship between Alzheimer’s disease (AD) biomarkers and subjective cognitive decline (SCD) is needed for better defining its clinical meaning in preclinical AD (preAD). Objective: To assess the association between the Subjective Cognitive Decline Questionnaire (SCD-Q), gray matter (GM), and cerebrospinal fluid amyloid-β (Aβ). Methods: 56 cognitively healthy older adults and their informants answered the SCD-Q. Correlations between GM and SCD-Q scores were explored using structural voxel-based morphometry models including Aβ levels. SCD-Q* Aβ vectors were calculated with higher scores reflecting higher SCD and cerebral amyloid, simultaneously. Subjects were classified according to their perception …of cognitive worsening in the last two years, exploring for GM differences between-groups. Results: Higher self-reported SCD-Q scores correlated with reduced GM in the right frontal lobe and increased volumes in the occipital lobe, calcarine sulcus, fusiform gyrus, and cerebellum, while higher informant’s scores correlated with increased GM in the right middle temporal gyrus. Correlations were more significant for SCD-Q language items, self-complaints, and more positive than negative correlations were found. The SCD-Q* Aβ vectors were negatively associated with GM both in self and informant’s reports. Finally, lower Aβ levels related to lower GM in subjects who noticed cognitive worsening, but related to higher GM in subjects who have not noticed this decline. Conclusions: Our results suggest that SCD-Q scores relate with incipient brain changes that may be due to preAD. Independent studies are needed to confirm our observations. Show more

Keywords: Amyloid-β, gray matter, preclinical Alzheimer’s disease, subjective cognitive decline, subjective cognitive decline-questionnaire

DOI: 10.3233/JAD-190624

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1287-1302, 2019

Authors: Douglass, Amanda | Walterfang, Mark | Velakoulis, Dennis | Abel, Larry

Article Type: Research Article

Abstract: Background: Changes to visual search have shown specific patterns in a number of dementia subtypes. The cortical regions involved in the control of visual search overlap with the regions affected in behavioral variant frontotemporal dementia (bvFTD). Previous literature has examined visual search in bvFTD with smaller array sizes. Objective: To examine the pattern of behavior shown by bvFTD patients while undertaking visual search in the presence of larger numbers of distractors to model increased cognitive load. Methods: 15 bvFTD and 17 control participants undertook three visual search tasks: color, orientation, and conjunction searches. A wide range …of array sizes was used, from 16 to 100 items arranged as a square. Behavior was quantified using accuracy, response time, and eye movements. Results: BvFTD participants displayed a reduction in accuracy and an increased response time across all task types. BvFTD participants displayed an increase in number of objects examined and number of fixations made for color and conjunction tasks. Fixation duration was increased for orientation and conjunction (the more difficult tasks) but not color search. Results indicated the increase in time to response to be due to an increased intercept, with no significant difference in slope for the different tasks. Conclusion: BvFTD participants display a pattern of visual search behavior consisting of a decrease in accuracy, an increase in response time, and a corresponding increase in the number and length of eye movements made during visual search. The pattern seen corresponds to studies of frontal lobe damage, while differing in pattern from that seen in a range of other cognitive conditions. Show more

Keywords: Eye movements, frontotemporal dementia, search, visual scan-paths

DOI: 10.3233/JAD-190981

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1303-1312, 2019

Authors: Jia, Jianping | Ji, Yong | Feng, Tao | Ye, Qinyong | Peng, Dantao | Kuang, Weihong | Ning, Yuping | Liang, Zhihou | Fan, Dongsheng | Wei, Wenshi | Li, Yansheng | Xiao, Shifu

Article Type: Research Article

Abstract: Background: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. Objective: To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer’s disease (AD). Methods: The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: …Alzheimer’s Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. Results: 222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p  < 0.001) by 2.0 (95% CI: –3.0 to –1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p  = 0.001, p  < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). Conclusion: This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose. Show more

Keywords: Alzheimer’s disease, capsule, Chinese population, rivastigmine

DOI: 10.3233/JAD-190791

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1313-1322, 2019

Authors: Ali, Farhan | Baringer, Stephanie L. | Neal, Arianna | Choi, Esther Y. | Kwan, Alex C.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) has several hallmark features including amyloid-β (Aβ) plaque deposits and neuronal loss. Here, we characterized Aβ plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6–9-month-old 5xFAD mice harboring mutations associated with familial AD. We used immunofluorescence staining to compare three regions in the frontal cortex—prelimbic (PrL), cingulate (Cg, including Cg1 and Cg2), and secondary motor (M2) cortices—along with primary somatosensory (S1) cortex. We quantified the density of Aβ plaques, which showed significant laminar and regional vulnerability. There were more plaques of larger sizes in deep layers compared to superficial layers. Total plaque burden was higher in frontal …regions compared to S1. We also found layer- and region-specific differences across genotype in the density of PV interneurons. PV neuron density was lower in 5xFAD mice than wild-type, particularly in deep layers of frontal regions, with Cg (–50%) and M2 (–39%) exhibiting the largest reduction. Using in vivo two-photon imaging, we longitudinally visualized the loss of frontal cortical PV neurons across four weeks in the AD mouse model. Overall, these results provide information about Aβ deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable. Show more

Keywords: 5xFAD, amyloid-β , cingulate cortex, familial Alzheimer’s disease, frontal cortex, parvalbumin-positive neurons, plaques, secondary motor cortex

DOI: 10.3233/JAD-181190

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1323-1339, 2019

Authors: Liechti, Caroline | Caviezel, Marco P. | Müller, Stephan | Reichert, Carolin F. | Calabrese, Pasquale | Linnemann, Christoph | Melcher, Tobias | Leyhe, Thomas

Article Type: Research Article

Abstract: The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer’s disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not …present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents’ retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD. Show more

Keywords: Alzheimer’s disease, autobiographical memory, cognitive impairment, episodic memory, gray matter, hippocampus, historic events, magnetic resonance imaging, medial temporal lobe, voxel-based morphometry

DOI: 10.3233/JAD-190047

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1341-1352, 2019

Authors: Wang, Shao-Yang | Chen, Wei | Xu, Wei | Li, Jie-Qiong | Hou, Xiao-He | Ou, Ya-Nan | Yu, Jin-Tai | Tan, Lan

Article Type: Research Article

Abstract: Background: Neurofilament light chain (NFL) as a potential biomarker of neurodegenerative diseases has been studied in a number of studies. Thus, a comprehensive meta-analysis is warranted to assess NFL performance in neurodegenerative diseases. Objective: To assess the performance of NFL in blood and cerebrospinal fluid (CSF) as a biomarker for neurodegenerative diseases. Methods: A total of 36 studies with comparison of NFL level between individuals with neurodegenerative diseases and controls were retrieved from PubMed, Web of Science and Science Direct, and the ratio of means method and delta method based on the random-effect model were used …to analyze the differentiation of NFL between patients and controls. Results: Differentiation of CSF NFL between patients with neurodegenerative diseases and controls showed significant results. Although a few studies on blood NFL available were included in the meta-analysis, the results still showed a distinct possibility that NFL could be a potential biomarker for neurodegenerative diseases. NFL levels were increased significantly in dementias, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, and Huntington’s disease. By contrast, NFL levels were not increased in Parkinson’s disease (PD), although they were increased significantly in PD-related disorders (multiple system atrophy and progressive supranuclear palsy). Conclusions: In our study, in addition to PD, NFL was suggested to be a global diagnostic biomarker for neurodegenerative diseases. Moreover, it could be used in differential diagnosis of PD and PD-related disorders. However, it was worth noting that NFL was not appropriate for diagnosis or differential diagnosis without clinical symptoms and other auxiliary examinations. Show more

Keywords: Biomarkers, blood, cerebrospinal fluid, meta-analysis, neurodegenerative diseases, neurofilament light chain

DOI: 10.3233/JAD-190615

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1353-1361, 2019

Authors: Lennon, Jack C.

Article Type: Book Review

Abstract: This review of Dementia Reimagined: Building a Life of Joy and Dignity from Beginning to End by Dr. Tia Powell describes its unique, scientifically-informed approach to the topics of caring for family members with dementia within the confines of the current United States healthcare system and preparing for their long-term care. Her book serves to provide an important account of many difficulties confronted along the course of dementia, ultimately seeking compassionate, dignified care for a loved one during the many years following diagnosis that allow for the experiencing of life’s joys that are unique to each individual. This book …is tailored to a broad readership, providing information for all individuals caring for people with dementia, and maintains a candid voice as it relates to our pursuit of curative treatments for an incurable illness. This review raises further questions related to how autonomy and beneficence can be amplified when interdisciplinary conflicts arise, as well as how education reform may improve patient care. Show more

Keywords: Aging, Alzheimer’s disease, dementia, ethics, healthcare

DOI: 10.3233/JAD-190611

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1363-1365, 2019

Article Type: Other

DOI: 10.3233/JAD-199011

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1367-1379, 2019