Journal of Alzheimer's Disease - Volume 39, issue 1

Authors: Chancellor, Bree | Duncan, Angel | Chatterjee, Anjan

Article Type: Review Article

Abstract: Patients with dementias commonly experience neuropsychiatric symptoms that diminish their quality of life. Pharmacologic treatments for these symptoms are limited in their efficacy. In the absence of near-future prospects for a cure for degenerative dementias, treatments that improve neuropsychiatric symptoms and quality of life are needed. We explore the hypothesis that art therapy is useful in dementia by reviewing the extant literature. With appropriate structure, patients with dementia can produce and appreciate visual art. Case studies and several small trials suggest that art therapy engages attention, provides pleasure, and improves neuropsychiatric symptoms, social behavior, and self-esteem. Whether these benefits generalize …beyond the studio remains unknown. We offer a theoretical framework that motivates the use of art therapy and propose that clinical enquiry to establish methods, assess efficacy, and define optimal conditions for the use of art therapy in Alzheimer's and other dementing disorders is timely. Show more

Keywords: Alzheimer's disease, art therapy, behavioral neurology, flow theory, frontotemporal dementia, neuropsychiatry

DOI: 10.3233/JAD-131295

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 1-11, 2014

Authors: Allegri, Ricardo F. | Bartoloni, Leonardo | Iturry, Mónica | Romero, Carlos | Begué, Christián | Sevlever, Gustavo | Taratuto, Ana Lía

Article Type: Short Communication

Abstract: We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype …by histotyping. Show more

Keywords: Aphasia, MM1+2C subtype, MM2 cortical subtype, prion, sporadic Creutzfeldt-Jakob disease

DOI: 10.3233/JAD-130350

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 13-17, 2014

Authors: Galimberti, Daniela | Arosio, Beatrice | Fenoglio, Chiara | Serpente, Maria | Cioffi, Sara M.G. | Bonsi, Rossana | Rossi, Paolo | Abbate, Carlo | Mari, Daniela | Scarpini, Elio

Article Type: Short Communication

Abstract: We genotyped for the C9ORF72 hexanucleotide repeat expansion a population of 156 non-demented elderly subjects, recruited in a geriatric unit as control group for association studies in patients with Alzheimer's disease (AD), and found two carriers (1.2%). The first was referred for subjective memory complaints, at age 81. He was followed up until age 84 and did not develop dementia. The second was an 80-year old volunteer (spouse and caregiver of a patient with AD), non-demented at time of recruitment. We have not had information on her condition since that time. These results suggest that the penetrance of the mutation …is definitely incomplete. Show more

Keywords: C9ORF72 hexanucleotide repeat expansion, dementia, elderly, frontotemporal lobar degeneration, penetrance

DOI: 10.3233/JAD-131172

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 19-22, 2014

Authors: Dolzhanskaya, Natalia | Gonzalez, Michael A. | Sperziani, Fiorella | Stefl, Shannon | Messing, Jeffrey | Wen, Guang Y. | Alexov, Emil | Zuchner, Stephan | Velinov, Milen

Article Type: Short Communication

Abstract: Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30 s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However, brain autopsy demonstrated typical changes of Alzheimer's disease.

Keywords: Alzheimer's disease, fast progressing dementia, kufs disease, lysosomal inclusions, presenilin 1 mutation

DOI: 10.3233/JAD-131340

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 23-27, 2014

Authors: Xu, Huan | Lu, Bingwei | Zheng, Beijie | Tian, Jie | Qi, Bo | Deng, Yuxiao | He, Zhenzhou | Su, Diansan | Wang, Xiangrui

Article Type: Research Article

Abstract: Background: Increasingly more aged people with Alzheimer’s disease (AD) must undergo surgery with general anesthesia for various reasons. Knowing the potency of common inhaled anesthetics on AD patients is important to minimize the quantity of inhaled anesthetics. Previous studies indicated that transgenic AD mice were more resistant to the common inhaled anesthetics than were wild-type mice. However, transgenic AD mice are associated with early-onset familial AD, which accounts for only 5% of the total AD patients in the clinic. Confirming the results using other animal AD models is still necessary. Objective: The aim of this study was to …evaluate the potency of common inhaled anesthetics in another AD animal model, the senescence-accelerated mouse prone-8 (SAMP-8) model. Methods: The minimum alveolar concentration (MAC) was measured by tail clamping in the SAMP-8 and senescence-resistant-1 (SAMR-1) mice at 4, 6, 8, and 10 months of age (n = 13). A two-way ANOVA (age and strain as the two factors) was used to analyze the difference. Results: The statistical results showed that both the age and strain factors had significant effects on the MAC values. The MAC of the SAMP-8 mice was significantly lower than that of the SAMR-1 mice for the three inhaled anesthetics. The MAC values of the SAMP-8 mice decreased significantly with aging. Conclusions: The SAMP-8 mice were more sensitive to the three inhaled anesthetics than were the SAMR-1 mice. Show more

Keywords: Alzheimer's disease, inhaled anesthetics, minimum alveolar concentration, senescence-accelerated mouse

DOI: 10.3233/JAD-130902

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 29-34, 2014

Authors: Mathur, Shubha | Glogowska, Aleksandra | McAvoy, Elizabeth | Righolt, Christiaan | Rutherford, Jaclyn | Willing, Cornelia | Banik, Upama | Ruthirakuhan, Myuri | Mai, Sabine | Garcia, Angeles

Article Type: Research Article

Abstract: Using three-dimensional (3D) telomeric analysis of buccal cells of 82 Alzheimer's disease (AD) patients and cognitively normal age and gender-matched controls, we have for the first time examined changes in the 3D nuclear telomeric architecture of buccal cells among levels of AD severity based on five 3D parameters: i) telomere length, ii) telomere number, iii) telomere aggregation, iv) nuclear volume, and v) a/c ratio, a measure of spatial telomere distribution. Our data indicate that matched controls have significantly different 3D telomere profiles compared to mild, moderate, and severe AD patients (p < 0.0001). Distinct profiles were also evident for each …AD severity group. An increase in telomere number and aggregation concomitant with a decrease in telomere length from normal to severe AD defines the individual stages of the disease (p < 0.0001). Show more

Keywords: Alzheimer's disease, buccal mucosa, fluorescent in situ hybridization, genomic instability, three-dimensional image, telomeres

DOI: 10.3233/JAD-130866

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 35-48, 2014

Authors: Runtti, Hilkka | Mattila, Jussi | van Gils, Mark | Koikkalainen, Juha | Soininen, Hilkka | Lötjönen, Jyrki | for the Alzheimer's Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Several neuropsychological tests and biomarkers of Alzheimer's disease (AD) have been validated and their evolution over time has been explored. In this study, multiple heterogeneous predictors of AD were combined using a supervised learning method called Disease State Index (DSI). The behavior of DSI values over time was examined to study disease progression quantitatively in a mild cognitive impairment (MCI) cohort. The DSI method was applied to longitudinal data from 140 MCI cases that progressed to AD and 149 MCI cases that did not progress to AD during the follow-up. The data included neuropsychological tests, brain volumes from magnetic resonance …imaging, cerebrospinal fluid samples, and apolipoprotein E from the Alzheimer's Disease Neuroimaging Initiative database. Linear regression of the longitudinal DSI values (including the DSI value at the point of MCI to AD conversion) was performed for each subject having at least three DSI values available (147 non-converters, 126 converters). Converters had five times higher slopes and almost three times higher intercepts than non-converters. Two subgroups were found in the group of non-converters: one group with stable DSI values over time and another group with clearly increasing DSI values suggesting possible progression to AD in the future. The regression parameters differentiated between the converters and the non-converters with classification accuracy of 76.9% for the slopes and 74.6% for the intercepts. In conclusion, this study demonstrated that quantifying longitudinal patient data using the DSI method provides valid information for follow-up of disease progression and support for decision making. Show more

Keywords: Alzheimer's disease, biomarkers, data mining, decision support techniques, early diagnosis, mild cognitive impairment

DOI: 10.3233/JAD-130359

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 49-61, 2014

Authors: Blennerhassett, Richard | Lillo, Patricia | Halliday, Glenda M. | Hodges, John R. | Kril, Jillian J.

Article Type: Research Article

Abstract: Atypical presentations of Alzheimer's disease (AD) have been described, including a “frontal” variant (fvAD), which presents with personality change and executive dysfunction similar to that seen in behavioral variant frontotemporal dementia (bvFTD). This clinical variation is thought to reflect the regional distribution of pathology, although few reports include autopsy confirmation. We compared three clinicopathological groups matched for age at diagnosis and disease duration; those with possible bvFTD who at autopsy had only AD (fvAD), those with typical AD clinically and pathologically, and those with typical clinical bvFTD confirmed pathologically. The density of neurons and AD-type pathology was quantified in the …frontal association, occipital association, and entorhinal cortices and hippocampal CA1 regions. Immunohistochemistry for phosphorylated tau and amyloid-β deposition was used to detect neurofibrillary tangles and plaques. Of the six core clinical features of the International Consensus Criteria, disinhibition, stereotyped behaviors, and executive dysfunction were most common, occurring in five of the six fvAD patients. Other features were rare. While there was no significant difference in neuron density between groups for any of the four regions, when the ratio of frontal:occipital pathology was examined, neuronal density in fvAD was significantly less than AD but similar to bvFTD. The frontal:occipital ratio of AD-type pathology was also greater in fvAD than AD. The findings of this study suggest a frontal variant of AD exists with features that mimic bvFTD and that this reflects a differential distribution of neurodegeneration with more marked pathology in the frontal cortex compared with the occipital cortex. Show more

Keywords: Amyloid-β plaques, neurofibrillary tangles, neuronal loss

DOI: 10.3233/JAD-131241

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 63-70, 2014

Authors: Bachman, Alvin H. | Lee, Sang Han | Sidtis, John J. | Ardekani, Babak A.

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) has been shown to be associated with shrinkage of the corpus callosum mid-sagittal cross-sectional area (CCA). Objective: To study temporal rates of corpus callosum atrophy not previously reported for early AD. Methods: We used longitudinal MRI scans to study the rates of change of CCA and circularity (CIR), a measure of its shape, in normal controls (NC, n = 75), patients with very mild AD (AD-VM, n = 51), and mild AD (AD-M, n = 21). Results: There were significant reduction rates in CCA and CIR in all three groups. …While CCA reduction rates were not statistically different between groups, the CIR declined faster in AD-VM (p < 0.03) and AD-M (p < 0.0001) relative to NC, and in AD-M relative to AD-VM (p < 0.0004). Conclusion: CIR declines at an accelerated rate with AD severity. Its rate of change is more closely associated with AD progression than CCA or any of its sub-regions. CIR may be a useful group biomarker for objective assessment of treatments that aim to slow AD progression. Show more

Keywords: Alzheimer's disease, brain, circularity, corpus callosum, magnetic resonance imaging, shape analysis

DOI: 10.3233/JAD-131526

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 71-78, 2014

Authors: Wang, Hao | Yu, Yang | Chen, Wei | Cui, Yingjie | Luo, Tian | Ma, Jian | Jiang, Xian-Cheng | Qin, Shucun

Article Type: Research Article

Abstract: Increased expression of phospholipid transfer protein (PLTP) was observed in the brains of Alzheimer's disease (AD) patients; however, the role of PLTP in the progress of AD is still poorly understood. The objective of this study was to evaluate the effect of PLTP deficiency on the recognition and metabolism of amyloid-β (Aβ) in mice. We performed the Morris water maze to determine the learning and memory capabilities of 50-week age wild type mice (WT, n = 12) and PLTP knockout mice (PLTP−/−, n = 12). The levels of Aβ and amyloid-β protein precursor (AβPP) were examined by ELISA and western …blot, respectively. The levels and activity of β- and γ-secretases were determined by western blot and activity assay kit, respectively. Morris water maze results showed that PLTP deficiency significantly impaired recognition compared with WT mice. Levels of Aβ42 in the cortex and hippocampus was significantly increased, yet the levels of Aβ40 in the cortex was decreased in PLTP−/− compared with WT mice. No typical senile plaques were found in the WT or PLTP−/− mice. AβPP expression and β-secretase activity were both significantly increased in PLTP−/− mice. Moreover, PLTP deficiency increased the expression of γ-secretase catalytic units and decreased the content of apolipoprotein E. Therefore we concluded that PLTP deficiency impaired cognition and aggravated AD by enhancing the generation of Aβ in the cortex of old mice. Show more

Keywords: Amyloid-β, amyloid-β protein precursor, capabilities of learning and memory, phospholipid transfer protein

DOI: 10.3233/JAD-130812

Citation: Journal of Alzheimer's Disease, vol. 39, no. 1, pp. 79-88, 2014