Journal of Alzheimer's Disease - Volume 66, issue 2

Authors: Frank, Lori | Wesson Ashford, J. | Bayley, Peter J. | Borson, Soo | Buschke, Herman | Cohen, Donna | Cummings, Jeffrey L. | Davies, Peter | Dean, Margaret | Finkel, Sanford I. | Hyer, Lee | Perry, George | Powers, Richard E. | Schmitt, Frederick

Article Type: Editorial

Abstract: The availability and increasing popularity of direct-to-consumer genetic testing for the presence of an APOE4 allelle led the Alzheimer’s Foundation of America Medical, Scientific and Memory Screening Advisory Board to identify three critical areas for attention: 1) ensure consumer understanding of test results; 2) address and limit potential negative consequences of acquiring this information; and 3) support linking results with positive health behaviors, including potential clinical trial participation. Improving access to appropriate sources of genetic counseling as part of the testing process is critical and requires action from clinicians and the genetic testing industry. Standardizing information and resources across the …industry should start now, with the input of consumers and experts in genetic risk and health information disclosure. Direct-to-consumer testing companies and clinicians should assist consumers by facilitating consultation with genetic counselors and facilitating pursuit of accurate information about testing. Show more

Keywords: APOE, genetic risk, genetic testing, late-onset Alzheimer’s disease

DOI: 10.3233/JAD-180629

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 421-423, 2018

Authors: Krolak-Salmon, Pierre | Dubois, Bruno | Sellal, François | Delabrousse-Mayoux, Jean-Philippe | Vandel, Pierre | Amieva, Hélène | Jeandel, Claude | Andrieu, Sandrine | Perret-Liaudet, Armand

Article Type: Editorial

Abstract: The French Minister of Health published a decree on May 29th of 2018 removing the drugs used to fight against symptoms due to Alzheimer’s disease (donepezil, rivastigmine, galantamine, memantine) from the list of available reimbursed drugs. This follows the advice delivered by the High Authority for Health in 2016 and 2018 stating an “insufficient medical benefit and dangerousness because of significant side effects”. The main French scientific and medical societies and professional associations want to state here their deep disagreement regarding this unfair decision. The evidence-based medicine related to these drugs reaches a high level in literature, whereas the clinical …relevance of these treatments must be considered with co-prescription of psychosocial interventions and related approaches. As no serious pharmacovigilance signal has been provided by health authorities, the ratio of benefits/risks favors these drugs. Show more

Keywords: Alzheimer’s disease, drug, health policy, reimbursement

DOI: 10.3233/JAD-180843

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 425-427, 2018

Authors: Pluta, Ryszard | Ułamek-Kozioł, Marzena | Januszewski, Sławomir | Czuczwar, Stanisław J.

Article Type: Review Article

Abstract: Brain ischemia comprises blood-brain barrier, glial, and neuronal cells. The blood–brain barrier controls permeability of different substances and the composition of the neuronal cells ‘milieu’, which is required for their physiological functioning. Recent evidence indicates that brain ischemia itself and ischemic blood-brain barrier dysfunction is associated with the accumulation of neurotoxic molecules within brain tissue, e.g., different parts of amyloid-β protein precursor and changed pathologically tau protein. All these changes due to ischemia can initiate and progress neurodegeneration of the Alzheimer’s disease-type. This review presents brain ischemia and ischemic blood-brain barrier as a trigger for tau protein alterations. Thus, we …hypothesize that the changes in pattern of phosphorylation of tau protein are critical to microtubule function especially in neurons, and contribute to the neurodegeneration following brain ischemia-reperfusion episodes with Alzheimer’s disease phenotype. Show more

Keywords: Blood-brain barrier, brain ischemia, dementia, experimental, gene expression, human, neurodegeneration, neuronal death, stroke, tau protein

DOI: 10.3233/JAD-180772

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 429-437, 2018

Authors: Lomiguen, Christine | Vidal, Luis | Kozlowski, Piotr | Prancan, Arthur | Stern, Robert

Article Type: Research Article

Abstract: Chitin is a β-linked straight chain carbohydrate matrix monopolymer prominent in invertebrates, from fungi to arthropods. Surprisingly, chitin is now documented in vertebrates, including humans, a component of vertebrate physiology that has been neglected until now. Chitin levels are elevated in Alzheimer’s disease (AD) patients, not only in the central nervous system but also in the cerebrospinal fluid and plasma. Elevated levels of chitin lectin have been reported in patients with AD. Chitinase activity varies widely in the human population. Chitin levels can increase in individuals with intrinsically low chitinase activity. Elevated amounts of chitin can reflect accumulation of the …small chitin fragments that remain wherever rapid hyaluronan synthesis occurs. Another source of chitin may be from remote fungal infections. Chitin can be toxic for neurons, and its accumulation may lead to the development of AD. We present new suggestions for animal models and treatment modalities that could prove useful in future research endeavors. An unexpected connection with Gaucher’s disease patients and their heterozygote relatives is also identified. These chitin-related mechanisms are novel approaches to AD whose etiology until now has defied explication. Show more

Keywords: Alzheimer’s disease, chitin, chitin lectins, chitinase, hyaluronan, neurodegenerative disorders

DOI: 10.3233/JAD-180326

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 439-444, 2018

Authors: Di Battista, Maria Elena | Dell’Acqua, Carola | Baroni, Luciana | Fenoglio, Chiara | Galimberti, Daniela | Gallucci, Maurizio

Article Type: Short Communication

Abstract: We describe the case of a 61-year-old woman diagnosed with Borreliosis at the age of 57. Subsequently, the patient developed depression, anxiety, and behavioral disturbances. A lumbar puncture excluded the condition of Neuroborreliosis. The diagnostic workup included: an MRI scan, a 18 F-FDG PET, a 123 I-ioflupane-SPECT, an amyloid-β PET, a specific genetic analysis, and a neuropsychological evaluation. Based on our investigation, the patient was diagnosed with probable behavioral-frontotemporal dementia (bvFTD), whereas in the previous years, the patient had been considered firstly as a case of Post-Treatment-Lyme Disease and, secondly, a psychiatric patient. We believe that, in the present case, …such initial symptoms of Borrelia infection may have superimposed on those of bvFTD rather than playing as a contributory cause. Show more

Keywords: Borrelia, depression, frontotemporal dementia, Lyme disease, misdiagnosis, post-treatment Lyme disease

DOI: 10.3233/JAD-180524

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 445-451, 2018

Authors: Vasquez, Velmarini | Mitra, Joy | Perry, George | Rao, K.S. | Hegde, Muralidhar L.

Article Type: Short Communication

Abstract: Altered expression of α-synuclein is linked to Parkinson’s disease (PD). A major challenge to explore how the increased α-synuclein affect neurotoxicity is the lack of a suitable human neuronal cell model that mimics this scenario. Its expression in neural precursors affects their differentiation process, in addition to the neuronal adaptability and variability in maintaining a constant level of expression across passages. Here, we describe an SH-SY5Y line harboring Tet-ON SNCA cDNA cassette that allows for induction of controlled α-synuclein expression after neuronal differentiation, which can be an important tool for PD research.

Keywords: α-synuclein, dopaminergic neurons, inducible α-synuclein expressing neuronal model for PD, Parkinson’s disease

DOI: 10.3233/JAD-180610

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 453-460, 2018

Authors: Turchetta, Chiara Stella | Perri, Roberta | Fadda, Lucia | Caruso, Giulia | De Simone, Maria Stefania | Caltagirone, Carlo | Carlesimo, Giovanni Augusto

Article Type: Research Article

Abstract: Patients with Alzheimer’s disease (AD) demonstrate a disproportionately larger forgetting rate in episodic memory tasks. Previous studies documented that, in comparison with healthy controls, the increased forgetting manifested by AD patients in word list recall tasks is confined to the recency portion of the list with normal forgetting rates on the primacy and mid-list portions. In this study we compared the primacy, mid-list, and recency ratios, obtained by dividing the immediate and delayed recall of words in position 1–4, 5–11, and 12–15 of a 15-word list, in different groups of demented patients, i.e., AD, frontal variant of frontotemporal dementia (fvFTD), …Lewy body disease (LBD), subcortical ischemic vascular dementia (SIVD), and a group of normal controls (NC). The aim was to investigate whether the above reported forgetting pattern would differentiate AD performance from that of other dementia groups. Results of the statistical analysis showed that only the recency ratio differentiated AD from patients in the other dementia groups. Consistently, hierarchical logistic regression analyses demonstrated that the recency ratio discriminated between AD patients and individuals affected by other forms of dementia. In particular, the discrimination power was high in differentiating AD from fvFTD patients but was less accurate in differentiating AD from LBD and SIVD patients. We assume that the increased forgetting in AD patients is due to a deficit in memory consolidation mechanisms (specific to AD) that prevent the terminal items in a list from being transferred from a temporary short-term memory store to a stable long-term memory store. Show more

Keywords: Alzheimer’s disease, dementia, forgetting rate, memory disorders, recency effect

DOI: 10.3233/JAD-180690

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 461-470, 2018

Authors: Vecchio, Fabrizio | Miraglia, Francesca | Quaranta, Davide | Lacidogna, Giordano | Marra, Camillo | Rossini, Paolo Maria

Article Type: Research Article

Abstract: Electroencephalographic (EEG) rhythms are linked to any kind of learning and cognitive performance including motor tasks. The brain is a complex network consisting of spatially distributed networks dedicated to different functions including cognitive domains where dynamic interactions of several brain areas play a pivotal role. Brain connectome could be a useful approach not only to mechanisms underlying brain cognitive functions, but also to those supporting different mental states. This goal was approached via a learning task providing the possibility to predict performance and learning along physiological and pathological brain aging. Eighty-six subjects (22 healthy, 47 amnesic mild cognitive impairment, 17 …Alzheimer’s disease) were recruited reflecting the whole spectrum of normal and abnormal brain connectivity scenarios. EEG recordings were performed at rest, with closed eyes, both before and after the task (Sensory Motor Learning task consisting of a visual rotation paradigm). Brain network properties were described by Small World index (SW), representing a combination of segregation and integration properties. Correlation analyses showed that alpha 2 SW in pre-task significantly predict learning (r  =  –0.2592, p  < 0.0342): lower alpha 2 SW (higher possibility to increase during task and better the learning of this task), higher the learning as measured by the number of reached targets. These results suggest that, by means of an innovative analysis applied to a low-cost and widely available techniques (SW applied to EEG), the functional connectome approach as well as conventional biomarkers would be effective methods for monitoring learning progress during training both in normal and abnormal conditions. Show more

Keywords: Alpha band, Alzheimer’s disease, EEG, eLORETA, functional brain connectivity, graph theory, learning, mild cognitive impairment, precision medicine

DOI: 10.3233/JAD-180342

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 471-481, 2018

Authors: Sacuiu, Simona | Eckerström, Marie | Johansson, Lena | Kern, Silke | Sigström, Robert | Xinxin, Guo | Östling, Svante | Skoog, Ingmar

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) has low predictive value for incident dementia. Objectives: We examined whether CT detectable brain changes add predictive value to SCD in a population sample with high scores on the Mini-Mental State Examination. Methods: Subjective reports of memory and executive function were gathered in a non-demented population sample ≥70 years (n  = 921). CT-brain was performed at baseline (n  = 626). Brain atrophy, infarcts, and white matter lesions (WMLs) were classified using visual ratings. Dementia incidence was evaluated periodically during 12 years. Results: The prevalence of SCD was 32.5% among individuals without …dementia. During follow-up, 151 individuals (16.4%) developed dementia. The risk of dementia was increased in SCD, and increased further with WMLs and cortical atrophy present. However, the positive predictive values for incident dementia were low, 25% in SCD and 41% in SCD with WMLs and cortical atrophy. Conclusion: Our observations add clinical value to the use of SCD and CT to select relevant populations for interventions against dementia, but more stringent screening methods are necessary to reach individuals at risk. Show more

Keywords: Cognitive dysfunction, dementia, neuroimaging, subjective, white matter

DOI: 10.3233/JAD-180073

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 483-495, 2018

Authors: Song, Ya-Nan | Wang, Ping | Xu, Wei | Li, Jie-Qiong | Cao, Xi-Peng | Yu, Jin-Tai | Tan, Lan

Article Type: Research Article

Abstract: Background: The conclusions about risk factors for rapid cognitive decline (RCD) in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) remain contradictory. Objective: To explore the factors predicting RCD in AD and MCI. Methods: We searched the PubMed, EMBASE, and the Cochrane Library from inception to May 27, 2017 for studies investigating factors associated with faster cognitive progression in AD and MCI. Effect sizes were meta-analyzed using fixed-effects and random-effects models. Results: Fifty-three studies with 14,330 patients (12,396 AD and 1,934 MCI) were included in the systematic review. The following factors were identified to …increase the risk of RCD in AD: Apolipoprotein E4 (ApoE4) (SMD [95% CI]: 0.52 [0.06,0.98]), early age at onset (SMD [95% CI]: –0.42 [–0.71, –0.13]), high level of education (RR = 2.05, 95% CI = 1.26 to 3.33), early appearance of extrapyramidal signs (RR = 2.18; 95% CI = 1.30 to 3.67), and neuropsychiatric conditions including hallucination (RR = 2.01, 95% CI = 1.40 to 2.87), strolling (RR = 1.99, 95% CI = 1.38 to 2.86), agitation (RR = 1.66, 95% CI = 1.23 to 2.24), and psychosis (RR = 1.42, 95% CI = 1.07 to 1.89). Instead, advanced age (≥75 years) (RR = 0.96, 95% CI = 0.93 to 0.99), diabetes (RR = 0.57; 95% CI = 0.35 to 0.93), and multidrug therapy (RR = 0.61, 95% CI = 0.60 to 0.62) would lower the risk of RCD. Furthermore, systematic research also reviewed seven risk factors associated with RCD in MCI. Conclusion: ApoE4, early onset, early appearance of extrapyramidal signs, high education level, and neuropsychiatric conditions might increase the risk of RCD while older age, diabetes, and multidrug therapy were the protective factors for AD. Show more

Keywords: Alzheimer’s disease, meta-analysis, mild cognitive impairment, rapid cognitive decline, risk factor, systematic review

DOI: 10.3233/JAD-180476

Citation: Journal of Alzheimer's Disease, vol. 66, no. 2, pp. 497-515, 2018