Journal of Alzheimer's Disease - Volume 51, issue 1

Authors: Kumfor, Fiona | Teo, Drusilla | Miller, Laurie | Lah, Suncica | Mioshi, Eneida | Hodges, John R. | Piguet, Olivier | Irish, Muireann

Article Type: Research Article

Abstract: Background: Autobiographical memory (ABM) refers to the capacity to remember one’s own past, and is known to be central for supporting one’s identity and sense of self. This capacity is commonly affected in Alzheimer’s disease (AD), as well as semantic dementia (SD) and behavioral-variant frontotemporal dementia (bvFTD). Importantly, ABM plays a critical social function, facilitating relationship intimacy and empathy, and thus loss of ABM may also negatively affect families and carers. Objective: To explore the relationship between ABM disruption and carer burden in AD, SD, and bvFTD, and establish whether characteristic ABM profiles differentially relate to carer burden …across dementia syndromes. Methods: We recruited 12 AD, 10 SD, and 13 bvFTD patients and their primary carer. All participants completed the Autobiographical Interview to assess memory for recent and remote events. Carers completed: the Zarit Burden Interview; Depression, Anxiety and Stress Scale (DASS-21); and the Intimate Bond Measure (IBM). Results: In AD, loss of recent ABM was associated with worse psychological wellbeing of carers on the DASS-21. In contrast in SD, remote ABM dysfunction was associated with SD patients showing greater controlling behavior within their intimate relationships. In bvFTD, surprisingly, despite pervasive ABM impairment, no relationship between extent of ABM loss and carer burden was observed. Conclusion: These preliminary results reveal that ABM impairment impacts on patients’ families and carers and suggest that these influences vary according to the pattern of ABM dysfunction. Disease-specific interventions focusing on preserved aspects of ABM may improve quality of life for both patients and carers. Show more

Keywords: Alzheimer’s disease, frontotemporal dementia, quality of life, relationships, semantic dementia, wellbeing

DOI: 10.3233/JAD-150740

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 237-248, 2016

Authors: Premi, Enrico | Cauda, Franco | Costa, Tommaso | Diano, Matteo | Gazzina, Stefano | Gualeni, Vera | Alberici, Antonella | Archetti, Silvana | Magoni, Mauro | Gasparotti, Roberto | Padovani, Alessandro | Borroni, Barbara

Article Type: Research Article

Abstract: In light of future pharmacological interventions, neuroimaging markers able to assess the response to treatment would be crucial. In Granulin (GRN ) disease, preclinical data will prompt pharmacological trials in the future. Two main points need to be assessed: 1) to identify target regions in different disease stages and 2) to determine the most accurate functional and structural neuroimaging index to be used. To this aim, we have taken advantage of the multivariate approach of multi-voxel pattern analysis (MVPA) to explore the information of brain activity patterns in a cohort of GRN Thr272fs carriers at different disease stages …(14 frontotemporal dementia (FTD) patients and 17 asymptomatic carriers) and a group of 33 healthy controls. We studied structural changes by voxel-based morphometry (VBM), functional connectivity by assessing salience, default mode, fronto-parietal, dorsal attentional, executive networks, and local connectivity by regional homogeneity, amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), degree centrality, and voxel-mirrored homotopic connectivity. In FTD patients with GRN mutation, the most predictive measure was VBM structural analysis, while in asymptomatic carriers the best predictor marker was the local connectivity measure (fALFF). Altogether, all indexes demonstrated fronto-temporo-parietal damage in GRN pathology, with widespread structural damage of fronto-parietal and temporal regions when disease is overt. MVPA could be of aid in identifying the most accurate neuroimaging marker for clinical trials. This approach was able to identify both the target region and the best neuroimaging approach, which would be specific in the different disease stages. Further studies are needed to simultaneously integrate multimodal indexes in a classifier able to trace the disease progression moving from preclinical to clinical stage of the disease. Show more

Keywords: Degree centrality, fractional amplitude of low frequency fluctuation, frontotemporal dementia, granulin, multivoxel pattern analysis, regional homogeneity, resting state fMRI, support vector machine learning, voxel-mirrored homotopic connectivity

DOI: 10.3233/JAD-150340

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 249-262, 2016

Authors: Haworth, Judy | Phillips, Michelle | Newson, Margaret | Rogers, Peter J. | Torrens-Burton, Anna | Tales, Andrea

Article Type: Research Article

Abstract: A substantial body of research evidence is indicative of disproportionately slowed information processing speed in a wide range of multi-trial, computer-based, neuroimaging- and electroencephalography-based reaction time (RT) tests in Alzheimer’s disease and mild cognitive impairment (MCI). However, in what is arguably a dichotomy between research evidence and clinical practice, RT associated with different brain functions is rarely assessed as part of their diagnosis. Indeed, often only the time taken to perform a single, specific task, commonly the Trail making test (TMT), is measured. In clinical practice therefore, there can be a failure to assess adequately the integrity of the rapid, …serial information processing and response, necessary for efficient, appropriate, and safe interaction with the environment. We examined whether a typical research-based RT task could at least match the TMT in differentiating amnestic MCI (aMCI) from cognitively healthy aging at group level. As aMCI is a heterogeneous group, typically containing only a proportion of individuals for whom aMCI represents the early stages of dementia, we examined the ability of each test to provide intra-group performance variation. The results indicate that as well as significant slowing in performance of the operations involved in TMT part B (but not part A), individuals with aMCI also experience significant slowing in RT compared to controls. The results also suggest that research-typical RT tests may be superior to the TMT in differentiating between cognitively healthy aging and aMCI at group level and in revealing the performance variability one would expect from an etiologically heterogeneous disorder such as aMCI. Show more

Keywords: Dementia, information processing speed, mild cognitive impairment, reaction time

DOI: 10.3233/JAD-150791

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 263-275, 2016

Authors: Bocchetta, Martina | Mega, Anna | Bernardi, Livia | Di Maria, Emilio | Benussi, Luisa | Binetti, Giuliano | Borroni, Barbara | Colao, Rosanna | Di Fede, Giuseppe | Fostinelli, Silvia | Galimberti, Daniela | Gennarelli, Massimo | Ghidoni, Roberta | Piaceri, Irene | Pievani, Michela | Porteri, Corinna | Redaelli, Veronica | Rossi, Giacomina | Suardi, Silvia | Babiloni, Claudio | Scarpini, Elio | Tagliavini, Fabrizio | Padovani, Alessandro | Nacmias, Benedetta | Sorbi, Sandro | Frisoni, Giovanni B. | Bruni, Amalia C. | SINdem

Collaborators: Bozzali, Marco | Parnetti, Lucilla | Ferrarese, Carlo | Cappa, Stefano F. | Marra, Camillo | Masullo, Carlo | Rainero, Innocenzo | Silani, Vincenzo | Sorrentino, Giuseppe | Bruno, Giuseppe | Cagnin, Annachiara

Article Type: Research Article

Abstract: Background: Genetic testing of familial Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) is attracting interest thanks to innovative primary prevention clinical trials and increased request for information by at-risk individuals. However, ethical, social, and psychological implications are paramount and genetic testing must be supported by structured genetic counseling. In Italy, practice parameters and guidelines for genetic counseling in dementia are not available. Objective: To develop a nationally harmonized protocol for genetic counseling and testing of familial AD and FTLD. Methods: Activities were carried out in the context of the Italian Dominantly Inherited Alzheimer’s and …Frontotemporal Network (IT-DIAfN) project, a national network of centers of excellence with expertise in managing patients with familial AD and FTLD. A survey of the literature on genetic counseling protocols and guidelines was conducted. Local protocols for genetic counseling were surveyed. Differences and commonalities among protocols were identified and discussed among project partners. Consensus was reached following implicit aggregation methods. Results: Consensus was reached on a protocol for patients with clinically diagnosed familial AD or FTLD and a distinct protocol for their at-risk relatives. Genetic counseling should be provided by a multidisciplinary team including a geneticist, a neurologist/geriatrician, and a psychologist/psychiatrist, according to the following schedule: (i) initial consultation with tailored information on the genetics of the dementias; (ii) clinical, psychological, and cognitive assessment; if deemed appropriate (iii) genetic testing following a structured decision tree for gene mutation search; (iv) genetic testing result disclosure; (v) psychological support follow-up. Conclusion: This genetic counseling protocol provides Italian centers with a line of shared practice for dealing with the requests for genetic testing for familial AD and FTLD from patients and at-risk relatives, who may also be eligible participants for novel prevention clinical trials. Show more

Keywords: Alzheimer’s disease, frontotemporal degeneration, genetic counseling, genetic testing

DOI: 10.3233/JAD-150849

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 277-291, 2016

Authors: Kim, Yong Hwan | Beak, Seung Han | Charidimou, Andreas | Song, Min

Article Type: Research Article

Abstract: Late onset Alzheimer’s disease (AD) and Parkinson’s disease (PD) are mostly “sporadic” age-related neurodegenerative disorders, but with a clear genetic component. However, their genetic architecture is complex and heterogeneous, largely remaining a conundrum, with only a handful of well-established genetic risk factors consistently associated with these diseases. It is possible that numerous, yet undiscovered, AD and PD related genes might exist. We focused on the ‘gene’ as a mediator to find new potential genes that might have a relationship with both disorders using bio-literature mining techniques. Based on Entrez Gene, we extracted the genes and directional gene-gene relation in the …entire MEDLINE records and then constructed a directional gene-gene network. We identified common genes associated with two different but related diseases by performing shortest path analysis on the network. With our approach, we were able to identify and map already known genes that have a direct relationship with PD and AD. In addition, we identified 7 genes previously unknown to be a bridge between these two disorders. We confirmed 4 genes, ROS1, FMN1, ATP8A2, and SNORD12C, by biomedical literature and further checked 3 genes, ERVK-10, PRS, and C7orf49, that might have a high possibility to be related with both diseases. Additional experiments were performed to demonstrate the effectiveness of our proposed method. Comparing to the co-occurrence approach, our approach detected 25% more candidate genes and verified 10% more genes that have the relationship between both diseases than the co-occurrence approach did. Show more

Keywords: Alzheimer’s disease, bio-textmining, literature-based discovery, Parkinson’s disease

DOI: 10.3233/JAD-150769

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 293-312, 2016

Authors: Pasquini, Lorenzo | Scherr, Martin | Tahmasian, Masoud | Myers, Nicholas E. | Ortner, Marion | Kurz, Alexander | Förstl, Hans | Zimmer, Claus | Grimmer, Timo | Akhrif, Atae | Wohlschläger, Afra M. | Riedl, Valentin | Sorg, Christian

Article Type: Research Article

Abstract: In Alzheimer’s disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD-dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. …Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial-parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity. Show more

Keywords: Alzheimer’s disease, atrophy, functional magnetic resonance imaging, hippocampus, medial-parietal cortex, medial-temporal lobe, neurodegeneration, neuroimaging, physiopathology, resting-state activity

DOI: 10.3233/JAD-150823

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 313-326, 2016

Article Type: Other

DOI: 10.3233/JAD-151171

Citation: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 327-331, 2016