Journal of Alzheimer's Disease - Volume 51, issue 3

Authors: Nishihira, Junko | Tokashiki, Takashi | Higashiuesato, Yasushi | Willcox, Donald Craig | Mattek, Nora | Shinto, Lynne | Ohya, Yusuke | Dodge, Hiroko H.

Article Type: Research Article

Abstract: Background: Epidemiological studies have found frequent consumption of fatty fish is protective against cognitive decline. However, the association between circulating omega-3 polyunsaturated fatty acid (PUFA) levels and cognitive functions among the oldest old is not well known. Objective: To examine the association between serum PUFA levels and cognitive function among community-dwelling, non-demented elderly aged over 80 years old. Methods: The data came from the Keys to Optimal Cognitive Aging (KOCOA) study; an ongoing cohort of relatively healthy volunteers aged over 80 years old, living in Okinawa, Japan. One hundred eighty five participants (mean age 84.1±3.4 years) …assessed in 2011 who were free from frank dementia (defined as Clinical Dementia Rating <1.0) were used for the current cross-sectional study. We examined whether serum omega-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), arachidonic acid (AA), EPA/AA ratio, DHA/AA ratio, and DHA+EPA are associated with (1) age and (2) global cognitive function (Japanese MMSE) and executive function (Verbal Fluency Letter). Data was analyzed univariately by t -test and multivariately by cumulative logistic regression models controlling for age, gender, years of education, obesity, hypertension, diabetes, and dyslipidemia. Results: Serum DHA levels decreased with increasing age (p  = 0.04). Higher global cognitive function was associated with higher levels of serum EPA (p  = 0.03) and DHA + EPA (p  = 0.03) after controlling for confounders. Conclusions: Higher serum EPA and DHA + EPA levels were independently associated with better scores on global cognitive function among the oldest old, free from dementia. Longitudinal follow-up studies are warranted. Show more

Keywords: Cognitive function, DHA, EPA, KOCOA, Okinawa, oldest old, non-demented subjects, PUFA

DOI: 10.3233/JAD-150910

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 857-866, 2016

Authors: Suppa, Per | Hampel, Harald | Kepp, Timo | Lange, Catharina | Spies, Lothar | Fiebach, Jochen B. | Dubois, Bruno | Buchert, Ralph | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: MRI-based hippocampus volume, a core feasible biomarker of Alzheimer’s disease (AD), is not yet widely used in clinical patient care, partly due to lack of validation of software tools for hippocampal volumetry that are compatible with routine workflow. Here, we evaluate fully-automated and computationally efficient hippocampal volumetry with FSL-FIRST for prediction of AD dementia (ADD) in subjects with amnestic mild cognitive impairment (aMCI) from phase 1 of the Alzheimer’s Disease Neuroimaging Initiative. Receiver operating characteristic analysis of FSL-FIRST hippocampal volume (corrected for head size and age) revealed an area under the curve of 0.79, 0.70, and 0.70 for prediction of …aMCI-to-ADD conversion within 12, 24, or 36 months, respectively. Thus, FSL-FIRST provides about the same power for prediction of progression to ADD in aMCI as other volumetry methods. Show more

Keywords: ADNI, Alzheimer’s disease, aMCI-to-Alzheimer’s disease dementia conversion, amnestic mild cognitive impairment, FSL-FIRST, fully-automated, hippocampal volumetry, magnetic resonance imaging, model-based segmentation, prediction

DOI: 10.3233/JAD-150804

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 867-873, 2016

Authors: Vallino Costassa, Elena | Fiorini, Michele | Zanusso, Gianluigi | Peletto, Simone | Acutis, Pierluigi | Baioni, Elisa | Maurella, Cristiana | Tagliavini, Fabrizio | Catania, Marcella | Gallo, Marina | Faro, Monica Lo | Chieppa, Maria Novella | Meloni, Daniela | D’Angelo, Antonio | Paciello, Orlando | Ghidoni, Roberta | Tonoli, Elisa | Casalone, Cristina | Corona, Cristiano

Article Type: Research Article

Abstract: Amyloid-β (Aβ) deposits are seen in aged individuals of many mammalian species that possess the same aminoacid sequence as humans. This study describes Aβ deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years. Extracellular and intracellular Aβ deposition was detected with 4G8 antibody in the cortex, hippocampus, and cerebellum. X-34 staining failed to stain Aβ deposits, indicating the non β-pleated nature of these deposits. Western blot analysis and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry revealed in Tris, Triton, and formic acid fractions the presence of different Aβ peptides, characterized mainly by C-terminally truncated forms. …Exploration of the genetic variability of APOE, PSEN1 , and PSEN2 genes involved in Alzheimer’s disease pathogenesis revealed several previously unreported polymorphisms. This study demonstrates certain similarities between Aβ deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging. Furthermore, the identification of the same Aβ peptides reported in humans, but unable to form aggregates, supports the hypothesis that cattle may be protected against amyloid plaque formation. Show more

Keywords: Aging, amyloid beta-protein, cattle, glial cells

DOI: 10.3233/JAD-151007

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 875-887, 2016

Authors: Wong, Stephanie | Bertoux, Maxime | Savage, Greg | Hodges, John R. | Piguet, Olivier | Hornberger, Michael

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) sometimes presents with prominent executive dysfunction and associated prefrontal cortex atrophy. The impact of such executive deficits on episodic memory performance as well as their neural correlates in AD, however, remains unclear. The aim of the current study was to investigate episodic memory and brain atrophy in AD patients with relatively spared executive functioning (SEF-AD; n  = 12) and AD patients with relatively impaired executive functioning (IEF-AD; n  = 23). We also compared the AD subgroups with a group of behavioral-variant frontotemporal dementia patients (bvFTD; n  = 22), who typically exhibit significant executive deficits, and age-matched healthy controls (n  = 38). …On cognitive testing, the three patient groups showed comparable memory profiles on standard episodic memory tests, with significant impairment relative to controls. Voxel-based morphometry analyses revealed extensive prefrontal and medial temporal lobe atrophy in IEF-AD and bvFTD, whereas this was limited to the middle frontal gyrus and hippocampus in SEF-AD. Moreover, the additional prefrontal atrophy in IEF-AD and bvFTD correlated with memory performance, whereas this was not the case for SEF-AD. These findings indicate that IEF-AD patients show prefrontal atrophy in regions similar to bvFTD, and suggest that this contributes to episodic memory performance. This has implications for the differential diagnosis of bvFTD and subtypes of AD. Show more

Keywords: Dementia, needs assessment, primary health care, randomized controlled trial

DOI: 10.3233/JAD-151016

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 889-903, 2016

Authors: Grangeon, Lou | Paquet, Claire | Bombois, Stephanie | Quillard-Muraine, Muriel | Martinaud, Olivier | Bourre, Bertrand | Lefaucheur, Romain | Nicolas, Gaël | Dumurgier, Julien | Gerardin, Emmanuel | Jan, Mary | Laplanche, Jean-Louis | Peoc’h, Katell | Hugon, Jacques | Pasquier, Florence | Maltête, David | Hannequin, Didier | Wallon, David | the collaborators of the ePLM.fr group

Article Type: Research Article

Abstract: Background: Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer’s disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses. Objective: Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD. Methods: Patients (n  = 202) …with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria. Results: Patients were diagnosed with AD (n  = 148, 73.2%), mixed dementia (n  = 38, 18.8%), CJD, vascular dementia (n  = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n  = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p  < 0.0001). Conclusion: Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarker, Creutzfeldt-Jakob disease, dementia, tau

DOI: 10.3233/JAD-151111

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 905-913, 2016

Authors: Simonovitch, Shira | Schmukler, Eran | Bespalko, Alina | Iram, Tal | Frenkel, Dan | Holtzman, David M. | Masliah, Eliezer | Michaelson, Danny M. | Pinkas-Kramarski, Ronit

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is the most prevalent form of dementia in elderly. Genetic studies revealed allelic segregation of the apolipoprotein E (ApoE) gene in sporadic AD and in families with higher risk of AD. The mechanisms underlying the pathological effects of ApoE4 are not yet entirely clear. Several studies indicate that autophagy, which plays an important role in degradation pathways of proteins, organelles and protein aggregates, may be impaired in AD. In the present study, we investigated the effects of ApoE4 versus the ApoE3 isoform on the process of autophagy in mouse-derived astrocytes. The results obtained reveal that under several …autophagy-inducing conditions, astrocytes expressing ApoE4 exhibit lower autophagic flux compared to astrocytes expressing ApoE3. Using an in situ model, we examined the role of autophagy and the effects thereon of ApoE4 in the elimination of Aβ plaques from isolated brain sections of transgenic 5xFAD mice. This revealed that ApoE4 astrocytes eliminate Aβ plaques less effectively than the corresponding ApoE3 astrocytes. Additional experiments showed that the autophagy inducer, rapamycin, enhances Aβ plaque degradation by ApoE4 astrocytes whereas the autophagy inhibitor, chloroquine, blocks Aβ plaque degradation by ApoE3 astrocytes. Taken together, these findings show that ApoE4 impairs autophagy in astrocyte cultures and that this effect is associated with reduced capacity to clear Aβ plaques. This suggests that impaired autophagy may play a role in mediating the pathological effects of ApoE4 in AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, apolipoprotein E4, autophagy

DOI: 10.3233/JAD-151101

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 915-927, 2016

Article Type: Meeting Report

DOI: 10.3233/JAD-160100

Citation: Journal of Alzheimer's Disease, vol. 51, no. 3, pp. 929-934, 2016