Journal of Alzheimer's Disease - Volume 39, issue 3

Authors: Kasahata, Naoki | Hagiwara, Mariko | Kato, Hiroyuki | Nakamura, Ayako | Uchihara, Toshiki

Article Type: Short Communication

Abstract: An 85-year-old man developed l-dopa responsive parkinsonism indistinguishable from Parkinson's disease and subsequent dementia, followed by supranuclear ophthalmoplegia and neck dorsiflexion at the terminal stage. Midbrain tegmentum and medial temporal lobe were atrophic on magnetic resonance imaging, while decreased blood flow was predominant in frontotemporal lobes, detected by 3D-SSP of 123I- IMP SPECT. Alzheimer-type pathology without Lewy body pathology was confirmed at autopsy. Substantia nigra showed mild degeneration and several neurofibrillary tangles without Lewy body pathology or progressive supranuclear palsy cytopathology. L-dopa responsive parkinsonism could be an initial manifestation of Alzheimer's disease, which should be included in the differential diagnosis.

Keywords: Alzheimer's disease, 3-iodobenzylguanidine, levodopa, Lewy bodies, Parkinsonian disorders, progressive supranuclear palsy, Tegmentum mesencephali

DOI: 10.3233/JAD-131508

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 471-476, 2014

Authors: Cumbo, Eduardo | Ligori, Leonarda Domenica

Article Type: Research Article

Abstract: Background: Behavioral and psychological symptoms of dementia (BPSD) occur in up to 80% of Alzheimer’s disease (AD) patients and represent one of the most common reasons for early institutionalization and increase in management costs. Objectives: This study evaluated the effects of four drugs (memantine, donepezil, rivastigmine, galantamine) in BPSD in AD patients. Methods: This was a prospective, longitudinal, randomized, open-label, 4-arm, parallel-group, 12-month clinical trial carried out in 177 AD patients. The severity of BPSD was evaluated at baseline and after treatment with memantine (n = 48), donepezil (n = 42), rivastigmine (n = 46), and …galantamine (n = 41), by using the Neuropsychiatric Inventory (NPI) and the Behavioural Pathology in Alzheimer’s Disease (BEHAVE-AD) scales. Results: The NPI and BEHAVE-AD total scores improved from baseline to month 12 in all groups. The improvements in both scales were statistically significant in the memantine, donepezil, and rivastigmine groups, but not in the galantamine group. Responder analyses showed that treatment with memantine and rivastigmine resulted in more patients improving on NPI and BEHAVE-AD score, respectively. Agitation/aggression was the NPI item with the highest improvements (significantly versus baseline in the memantine and in the rivastigmine groups), while aggression and anxiety/phobias were the mostly improved BEHAVE-AD items (significantly in the rivastigmine group for both and in the rivastigmine group only for anxiety/phobias). All treatments were well tolerated: most of adverse events reported were transient and of mild-to-moderate intensity. Conclusions: This study suggests that specific drugs for AD, especially memantine and rivastigmine, may be effective in the improvement of BPSD in patients with mild to moderate AD, without major side effects. Show more

Keywords: Alzheimer's disease, behavioral and psychological symptoms, donepezil, galantamine, memantine, rivastigmine

DOI: 10.3233/JAD-131190

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 477-485, 2014

Authors: Schwenk, Michael | Dutzi, Ilona | Englert, Stefan | Micol, William | Najafi, Bijan | Mohler, Jane | Hauer, Klaus

Article Type: Research Article

Abstract: Background: Translation of intensive exercise programs developed specifically for patients with dementia into clinical settings is lacking. Objective: To determine if a progressive resistance and functional training program, previously evaluated in dementia outpatients, can be implemented in a geriatric inpatient setting in order to improve motor performances in patients with dementia. Methods: Eligible patients in one ward of a German geriatric hospital were assigned to the intervention group (IG, n = 74) and received intensive exercise training specifically designed for patients with dementia. Patients in the second ward were observed as a control group (CG, n …= 74). All patients received usual care treatment. Primary endpoints were maximal lower extremity strength measured by a leg-press device and duration of the 5-chair-stand test for functional performance. Secondary outcomes included a number of parameters for strength and function. Results: The rehabilitation period averaged 18.1 ± 6.8 days. The IG significantly improved in both primary endpoints (change: maximal strength, IG: +51.9 ± 42.3% versus CG: +13.5 ± 51.8%, p < 0.001; functional performance, IG: −19.2 ± 22.3% versus CG: −3.8 ± 32.2% s, p = 0.037). Secondary outcomes confirmed effects for strength and some, but not all, functional parameters. Interestingly, low baseline motor status, but not cognitive status, predicted positive training response. Conclusion: An intensive exercise program can be implemented in a geriatric rehabilitation setting to improve motor performances in patients with dementia. Results suggest that an intensification of training is feasible in the target group and substantially increases the benefits in comparison to receiving usual care exercise only. Show more

Keywords: Cognitive impairment, dementia, exercise, geriatrics, rehabilitation, resistance training

DOI: 10.3233/JAD-130470

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 487-498, 2014

Authors: Perrin, Paul B. | Morgan, Matthew | Aretouli, Eleni | Sutter, Megan | Snipes, Daniel J. | Hoyos, Guillermo Ramirez | Buraye, Jacqueline Arabia | Arango-Lasprilla, Juan Carlos

Article Type: Research Article

Abstract: Research in Caucasian populations has begun to examine the broad associations between physical and mental health in dementia caregivers. However, the examination of this relationship in Latin America is largely absent from the literature despite the fact that the region will see a major increase in dementia cases over the next 20 years. The current study examined the associations between health-related quality of life (HRQOL) and mental health in 90 dementia caregivers from Colombia, South America. A canonical correlation found that higher caregiver HRQOL was related to better mental health, as expected. Caregivers with high vitality and low role limitations …due to physical problems tended to have low depression and high satisfaction with life. Follow-up multiple regressions found that caregiver role limitations due to physical problems was uniquely associated with satisfaction with life, whereas vitality, role limitations due to physical problems, and pain were uniquely associated with burden (although the pain effect was likely error due to a suppressor effect). Additionally, vitality and social functioning were uniquely negatively related to depression. Because of the extremely high overlap between these two sets of variables, dementia interventions are needed in Latin America that target both caregiver mental and physical health, as both likely operate in unison and influence each other. Show more

Keywords: Dementia caregivers, health related quality of life, Latin America, mental health

DOI: 10.3233/JAD-130764

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 499-509, 2014

Authors: Conde-Sala, Josep L. | Turró-Garriga, Oriol | Garre-Olmo, Josep | Vilalta-Franch, Joan | Lopez-Pousa, Secundino

Article Type: Research Article

Abstract: Cross-sectional studies report notable discrepancies between patient and caregiver ratings of the quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study aimed to identify the factors associated with any changes in QoL-p ratings and any discrepancies between patient and caregiver ratings of QoL-p. Three-year follow-up of a cohort of non-institutionalized patients (n = 119). QoL-p was assessed by the Quality of Life in AD (QoL-AD) scale. We analyzed the influence of functional and cognitive status and behavioral problems in patients, and burden and mental health in caregivers. Repeated measures analysis was applied to the scores of patients …and caregivers on the QoL-AD, and to the discrepancies between them. Generally, patients' own ratings remained stable over time (F3,116 = 0.9, p = 0.439), whereas caregiver ratings showed a decline (F3,116 = 9.4, p < 0.001). In the analysis of discrepancies, patients with anosognosia gave higher ratings (F1,117 = 11.9, p = 0.001), whereas caregiver ratings were lower when the patient showed greater agitation (F1,117 = 13.0, p < 0.001), apathy (F1,117 = 15.4, p < 0.001), and disabilities (F1,117 = 17.1, p < 0.001), and when the caregiver experienced greater burden (F1,117 = 9.0, p = 0.003) and worse mental health (F1,117 = 10.1, p = 0.003). Patient ratings of QoL-p remain generally stable over time, whereas those of caregivers show a decline, there being significant discrepancies in relation to specific patient and caregiver factors. Show more

Keywords: Alzheimer's disease, anosognosia, caregiver burden, caregivers, disabilities, longitudinal study, mental health, neuropsychiatric symptoms, patients, quality of life

DOI: 10.3233/JAD-131286

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 511-525, 2014

Authors: Xia, Mingrui | Wang, Zhiqun | Dai, Zhengjia | Liang, Xia | Song, Haiqing | Shu, Ni | Li, Kuncheng | He, Yong

Article Type: Research Article

Abstract: Neuroimaging studies have demonstrated that patients with Alzheimer's disease (AD) have remarkable focal grey matter loss and hypometabolism in the posteromedial cortex (PMC), which is composed of the precuneus and posterior cingulate cortex, suggesting an important association of the PMC with AD pathophysiology. Studies have also shown that the PMC is a structurally and functionally heterogeneous structure containing various subregions with distinct connectivity profiles. However, whether these PMC subregions show differentially disrupted connectivity patterns in AD remains largely unknown. Here, we addressed this issue by collecting resting-state functional MRI data from 32 AD patients and 38 healthy controls. We automatically …identified the PMC subregions using a graph-based module detection algorithm and then mapped the whole-brain functional connectivity pattern of each subregion. The functional connectivity analysis was followed by a hierarchical clustering analysis to classify each subregion. Three distinct spatial connectivity patterns were observed across the PMC subregions: the anterior dorsal zone was functionally connected with the sensorimotor cortex; the posterior dorsal zone was functionally connected with the frontoparietal cortex; and the central and ventral zones were functionally connected with the default-mode regions. Group comparison analysis revealed that all three functional systems were significantly disrupted in the AD patients compared to the controls and these disruptions were positively correlated with the patients' cognitive performance. Collectively, we showed that the subregions of the PMC exhibit differentially disrupted neuronal circuitry in AD patients, which provides new insight into the functional neuroanatomy of the human PMC and the alterations that may be relevant to disease. Show more

Keywords: Alzheimer's disease, connectome, dementia, functional magnetic resonance imaging, network, parietal lobe

DOI: 10.3233/JAD-131583

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 527-543, 2014

Authors: Kanyenda, Limbikani J. | Verdile, Guiseppe | Martins, Ralph | Meloni, Bruno P. | Chieng, Joanne | Mastaglia, Francis | Laws, Simon M. | Anderton, Ryan S. | Boulos, Sherif

Article Type: Research Article

Abstract: The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which is regulated by sterol carrier protein, reportedly modulates amyloid-β (Aβ), the neurotoxic peptide implicated in neuronal degeneration in Alzheimer's disease (AD). Given that high fat/cholesterol is linked to amyloid deposition in AD, we investigated if cholesterol and/or Aβ can alter CD147 expression in rat cortical neuronal cultures. Water-soluble cholesterol and Aβ42 dose-dependently increased CD147 protein expression, but reduced FL-AβPP protein expression. Cholesterol and Aβ42 treatment also increased lactate dehydrogenase release but to varying degrees. Upregulation of CD147 expression was probably mediated by oxidative stress, as …H2 O2 (3 μM) also induced CD147 protein expression in neuronal cultures. In light of these findings, we investigated if CD147 induction was cytoprotective, a compensatory response to injury, or alternatively, a cell death signal. To this end, we used recombinant adenovirus to overexpress human CD147 (in SH-SY5Y cells and primary cortical neurons), and pre-treated cultures with or without recombinant cyclophilin A (rCYPA) protein, prior to Aβ42 exposure. We showed that increased CD147 expression protected against Aβ42 , only when rCYPA protein was added to neuronal cultures. Together, our findings reveal potentially important relationships between cholesterol loading, CD147 expression, Aβ toxicity, and the putative involvement of CYPA protein in neuroprotection in AD. Show more

Keywords: Aβ42, Alzheimer's disease, CD147, cholesterol, cyclophilin A, neuroprotection

DOI: 10.3233/JAD-131442

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 545-556, 2014

Authors: Tzikas, Stergios | Schlak, Dennis | Sopova, Kateryna | Gatsiou, Aikaterini | Stakos, Dimitrios | Stamatelopoulos, Kimon | Stellos, Konstantinos | Laske, Christoph

Article Type: Research Article

Abstract: Background: Increasing evidence supports the role of cardiovascular risk factors in the development of Alzheimer’s disease (AD). Objective: In the present pilot study, we investigated plasma concentrations of myeloperoxidase (MPO) and its possible association with plasma amyloid-β (Aβ)1-42/1-40 ratio in AD patients and elderly healthy controls. Methods: The study sample included 28 AD patients and 27 elderly individuals with a normal cognitive status as a control group. The Mini-Mental Status Examination was used to determine the global cognition. MPO, Aβ1-40 , and Aβ1-42 plasma concentrations were measured by enzyme linked immunoabsorbent assays. …Results: AD patients showed significantly higher plasma concentrations of MPO in comparison to healthy elderly controls (AD versus healthy elderly controls (mean ± SD): 132.8 ± 114.8 ng/mL versus 55.0 ± 42.6 ng/mL; p = 0.002). MPO plasma concentrations showed a significant positive correlation in the whole sample with the presence of AD (ρ = 0.428, p < 0.001) and its stage (ρ = 0.331; p = 0.013) as well as with plasma concentrations of Aβ1-42 (ρ = 0.406; p = 0.004) and Aβ1-42/1-40 ratio (ρ = 0.354; p = 0.013). In a binary logistic regression model, plasma MPO concentrations were independently associated with the presence of AD (p = 0.014). Conclusion: AD patients showed significantly increased plasma levels of MPO, which could be an important molecular link between atherosclerosis and AD. Further studies should evaluate whether MPO may also be a useful biomarker and potential new treatment target in AD. Show more

Keywords: Alzheimer's disease, amyloid-β, dementia, myeloperoxidase

DOI: 10.3233/JAD-131469

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 557-564, 2014

Authors: Harris, Sarah E. | Davies, Gail | Luciano, Michelle | Payton, Antony | Fox, Helen C. | Haggarty, Paul | Ollier, William | Horan, Michael | Porteous, David J. | the Genetic and Environmental Risk for Alzheimer's disease (GERAD1) Consortium | Starr, John M. | Whalley, Lawrence J. | Pendleton, Neil | Deary, Ian J.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) and non-pathological cognitive aging have phenotypic similarities which may be influenced by an overlapping set of genetic variants. Genome-wide complex trait analysis estimates that common genetic variants account for about 24% of the variation contributing to liability for AD. It is also estimated that 24% of the variance of non-pathological cognitive aging is accounted for by common single nucleotide polymorphisms. However, although the APOE locus is associated with both AD and cognitive aging, it is not known to what extent other common genetic variants, with smaller effect sizes that influence both, overlap. We test the hypothesis that …polygenic risk for AD is associated with cognitive ability and cognitive change in about 3,000 non-demented older people (Cognitive Ageing Genetics England and Scotland-CAGES-consortium). We found no significant association of polygenic risk for AD with cognitive ability or cognitive change in CAGES, indicating that the genetic etiologies of AD and non-pathological cognitive decline differ. Show more

Keywords: Aging, Alzheimer's disease, cognition, cohort studies, genetics, polygenic traits

DOI: 10.3233/JAD-131058

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 565-574, 2014

Authors: Lyness, Scott A. | Lee, Ae Young | Zarow, Chris | Teng, Evelyn L. | Chui, Helena C.

Article Type: Research Article

Abstract: We compared the sensitivity and specificity of two delayed recall scores from the Modified Mini-Mental State (3MS) test with consensus clinical diagnosis to differentiate cognitive impairment due to Alzheimer's disease (AD) versus non-AD pathologies. At a memory disorders clinic, 117 cognitively impaired patients were administered a baseline 3MS test and received a contemporaneous consensus clinical diagnosis. Their brains were examined after death about 5 years later. Using logistic regression with forward selection to predict pathologically defined AD versus non-AD, 10-min delayed recall entered first (p = 0.001), followed by clinical diagnosis (p = 0.02); 1-min delayed recall did not enter. …10-min delayed recall scores ≤4 (score range = 0–9) were 87% sensitive and 47% specific in predicting AD pathology; consensus clinical diagnosis was 82% sensitive and 45% specific. For the 57 patients whose initial Mini-Mental State Examination scores were ≥19 (the median), 3MS 10-min delayed recall scores ≤4 showed some loss of sensitivity (80%) but a substantial gain in specificity (77%). In conclusion, 10-min delayed recall score on the brief 3MS test distinguished between AD versus non-AD pathology about 5 years before death at least as well as consensus clinical diagnosis that requires much more comprehensive information and complex deliberation. Show more

Keywords: Autopsy, consensus, dementia, memory disorders, Modified Mini-Mental State (3MS), neuropsychological tests, sensitivity and specificity

DOI: 10.3233/JAD-130524

Citation: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 575-582, 2014