Journal of Alzheimer's Disease - Volume 50, issue 2

Authors: Vijayaraghavan, Swetha | Darreh-Shori, Taher | Rongve, Arvid | Berge, Guro | Sando, Sigrid B. | White, Linda R. | Auestad, Bjørn H. | Witoelar, Aree | Andreassen, Ole A. | Ulstein, Ingun D. | Aarsland, Dag

Article Type: Research Article

Abstract: Background: A common polymorphism of the butyrylcholinesterase gene, the K-variant (BCHE-K) is associated with reduced butyrylcholinesterase (BuChE) activity. Insufficient studies exist regarding the frequency and role of BCHE-K in dementias. Objective: To determine the association of BCHE-K and APOE ɛ 4 with diagnosis and rate of cognitive decline in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) patients. Methods: Genomic DNA from 368 subjects (108 AD, 174 DLB, and 86 controls) from two routine clinical cohort studies in Norway; DemVest and TrønderBrain, were genotyped for BCHE-K and APOE ɛ …4. The mild dementia DemVest subjects received annual Mini-Mental State Examination assessments for five years. Results: BCHE-K frequency was lower in DLB (33.9% ; p  <  0.01) than in control subjects (51.2%), and was numerically lower in AD as well (38.9% ; p  = 0.11). More rapid cognitive decline was associated with the APOE ɛ 4 genotype, but not with the BCHE-K genotype. In an exploratory analysis of patients who completed all five follow-up visits, there was greater cognitive decline in BCHE-K carriers in the presence of the APOE ɛ 4 allele than in the absence of these polymorphisms. Conclusion: BCHE-K is associated with a reduced risk for AD and DLB whereas APOE ɛ 4 is associated with more rapid cognitive decline. The greater cognitive decline in individuals with both APOE ɛ 4 and BCHE-K alleles require prospective confirmation in well-controlled trials. Show more

Keywords: Apolipoprotein E genotype, butyrylcholinesterase-K, cognition, dementia, Mini-Mental State Examination

DOI: 10.3233/JAD-150750

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 567-576, 2016

Authors: Mudar, Raksha A. | Chiang, Hsueh-Sheng | Eroh, Justin | Nguyen, Lydia T. | Maguire, Mandy J. | Spence, Jeffrey S. | Kung, Fanting | Kraut, Michael A. | Hart Jr., John

Article Type: Research Article

Abstract: We examined the effects of amnestic mild cognitive impairment (aMCI) on behavioral (response times and error rates) and scalp-recorded event-related potential (ERP) measures of response execution and inhibition, using Go/NoGo tasks involving basic and superordinate semantic categorization. Twenty-five aMCI (16 F; 68.5±8 years) and 25 age- and gender-matched normal control subjects (16 F; 65.4±7.1 years) completed two visual Go/NoGo tasks. In the single car task, responses were made based on single exemplars of a car (Go) and a dog (NoGo) (basic). In the object animal task, responses were based on multiple exemplars of objects (Go) and animals (NoGo) (superordinate). The …aMCI subjects had higher commission errors on the NoGo trials compared to the control subjects, whereas both groups had comparable omission errors and reaction times during the Go trials. The aMCI subjects had significantly prolonged N2 ERP latency during Go and NoGo trials across tasks compared to the controls. Both groups showed similar categorization effects and response type effects in N2/P3 ERP latencies and P3 amplitude. Our findings indicate that altered early neural processing indexed by N2 latency distinguishes subjects with aMCI from controls during the Go/NoGo task. Prolonged Go-N2 latency in aMCI appears to precede behavioral changes in response execution, whereas prolonged NoGo-N2 latency underlies behavioral deterioration in response inhibition. Show more

Keywords: Categorization, cognition, electroencephalography, event-related potentials, Go/NoGo, mild cognitive impairment, semantics

DOI: 10.3233/JAD-150586

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 577-590, 2016

Authors: Makovac, Elena | Serra, Laura | Spanò, Barbara | Giulietti, Giovanni | Torso, Mario | Cercignani, Mara | Caltagirone, Carlo | Bozzali, Marco

Article Type: Research Article

Abstract: Behavioral disorders and psychological symptoms (BPSD) in Alzheimer’s disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: …Mood (i.e., anxiety and depression; ADmood ), Frontal (i.e., dishinibition and elation; ADfrontal ), and Psychotic (delusions and hallucinations; ADpsychotic ) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD. Show more

Keywords: Alzheimer’s disease, behavioral, grey matter, magnetic resonance imaging, white matter

DOI: 10.3233/JAD-150612

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 591-604, 2016

Authors: Koch, Giacomo | Di Lorenzo, Francesco | del Olmo, Miguel Fernandez | Bonní, Sonia | Ponzo, Viviana | Caltagirone, Carlo | Bozzali, Marco | Martorana, Alessandro

Article Type: Research Article

Abstract: Cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ), total tau (t-tau), and phosphorylated tau proteins are associated with different clinical progression in Alzheimer’s disease (AD). We enrolled forty newly diagnosed AD patients, who underwent lumbar puncture, and carried out a K-means cluster analysis based on CSF biomarkers levels, resulting in two AD patient groups: Cluster 1 showed relatively high levels of Aβ and low levels of tau; Cluster 2 showed relatively low levels of Aβ and high levels of tau. Cortical plasticity was tested using the intermittent and continuous theta burst stimulation (iTBS and cTBS) protocols evoking respectively long-term potentiation (LTP) …and depression (LTD). Cholinergic transmission was tested by the short-latency afferent inhibition protocol. Neurophysiological evaluation showed that the two AD groups differed in terms of cortical plasticity: after iTBS, Cluster 2 patients showed a remarkable reversal of LTP toward LTD that was not observed in Cluster 1. LTD and central cholinergic transmission did not differ between groups. Patients were assessed longitudinally with Mini-Mental State Examination at 6, 12, and 18 month follow-ups. Cluster 2 AD had a faster cognitive decline already evident at the 12 month follow-up. High tau CSF levels were associated with LTD-like cortical plasticity and faster clinical progression. These results suggest that more aggressive tau pathology is associated with prominent LTD-like mechanisms of cortical plasticity and faster cognitive decline. Show more

Keywords: Alzheimer’s disease, amyloid-beta, cortical plasticity, long-term depression, long-term potentiation, tau, transcranial magnetic stimulation

DOI: 10.3233/JAD-150813

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 605-616, 2016

Article Type: Other

DOI: 10.3233/JAD-151064

Citation: Journal of Alzheimer's Disease, vol. 50, no. 2, pp. 617-621, 2016