Journal of Alzheimer's Disease - Volume 49, issue 1

Authors: Pan, Yaoqian | Liu, Ruizhu | Terpstra, Erin | Wang, Yanqing | Qiao, Fangfang | Wang, Jin | Tong, Yigang | Pan, Bo

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and is considered to be the main cause of cognitive impairment in elderly people. The major symptom of AD is progressive dementia that eventually results in dysfunction of daily life. Due to the fact that AD has a long period of incubation before clinical symptoms emerge, the available therapeutic treatments can only improve the symptoms but not delay the progression of AD. Therefore, there is an urgent need to explore effective diagnostic approaches to catch and better treat the disease before clinical symptoms appear. Recent research revealed that abnormal …expression of certain miRNA could have a crucial role in the pathological process of neurodegenerative disease including AD. Furthermore, given that AD patients show increased level of miRNAs in the blood and cerebrospinal fluid, miRNAs are considered promising non-invasive candidates for AD diagnosis and prognosis. Here, we reviewed the current research related to implications of miRNAs during the development of AD, summarized of actively used approaches to identifying potential miRNA biomarkers in body fluids, and discussed the diagnostic potential of microRNAs as biomarkers for AD. Show more

Keywords: Alzheimer’s disease, biomarkers, microRNAs

DOI: 10.3233/JAD-150451

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 1-12, 2016

Authors: Ovsepian, Saak V. | O’Leary, Valerie B.

Article Type: Review Article

Abstract: A breakthrough in Alzheimer’s disease (AD) research came with the discovery of the link between activity-dependent release of amyloid-β (Aβ) from neurons and formation of amyloid plaques. Along with elucidating the cellular basis of behavioral-dependent fluctuations in Aβ levels in the brain, insights have been gained toward understanding the mechanisms that warrant selective vulnerability of various forebrain circuits to amyloid pathology. The notion of elevated activity as a source of excessive Aβ production and plaque formation is, however, in conflict with ample electrophysiological data, which demonstrate exceedingly intense activity (both intrinsic and synaptic) of neurons in several brain regions that …are spared or marginally affected by amyloid plaques of AD. Thus, the link between the functional load of brain circuits and their vulnerability to amyloidosis, while evident, is also complex and remains poorly understood. Here, we discuss emerging data suggestive of a major role for super-intense synchronous activity of cortical and limbic networks in excessive Aβ production and plaque formation. It is proposed that dense recurrent wiring of associative areas prone to epileptic seizures might be of critical relevance to their higher susceptibility to plaque pathology and related functional impairments. Show more

Keywords: Alzheimer’s disease, amyloid-β peptide, hetero-modal associative cortex, neuronal synchrony, non-convulsive seizure

DOI: 10.3233/JAD-150544

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 13-19, 2016

Authors: Whitehouse, Peter J. | George, Daniel R.

Article Type: Editorial

DOI: 10.3233/JAD-150663

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 21-25, 2016

Authors: Tumminelli, Gemma | Di Donato, Ilaria | Guida, Valentina | Rufa, Alessandra | De Luca, Alessandro | Federico, Antonio

Article Type: Short Communication

Abstract: Oculodentodigital dysplasia (ODDD) [MIM 164200] is a rare disorder caused by mutations in the gap junction alpha 1 (GJA1 ) gene encoding for connexin 43 (Cx43). Typical signs include type III syndactyly, microphtalmia, microdontia, and neurological disturbances. We report a 59-year-old man having clinical symptoms and signs suggestive of ODDD, with some rarely reported features, that is the presence of gross calcifications of basal ganglia and cerebellar nuclei. Mutation analysis of GJA1 gene identified an unreported heterozygous missense mutation [NM_000165.3:c.124 G>C;p.(Glu42Gln)], which may be thought to alter the brain microvessels leading to massive calcifications, as in primary familial brain calcification.

Keywords: Basal ganglia calcification, GJA1 gene, oculodentodigital dysplasia

DOI: 10.3233/JAD-150424

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 27-30, 2016

Authors: Kinsella, Glynda J. | Ames, David | Storey, Elsdon | Ong, Ben | Pike, Kerryn E. | Saling, Michael M. | Clare, Linda | Mullaly, Elizabeth | Rand, Elizabeth

Article Type: Research Article

Abstract: Background: Governments are promoting the importance of maintaining cognitive health into older age to minimize risk of cognitive decline and dementia. Older people with amnestic mild cognitive impairment (aMCI) are particularly vulnerable to memory challenges in daily activities and are seeking ways to maintain independent living. Objective: To evaluate the effectiveness of memory groups for improving memory strategies and memory ability of older people, especially those with aMCI. Methods: 113 healthy older adults (HOA) and 106 adults with aMCI were randomized to a six-week memory group or a waitlist control condition. Outcome was evaluated through knowledge …and use of memory strategies, memory ability (self-report and neuropsychological tests), and wellbeing. Assessments included a six-month follow-up. Results: Using intention to treat analyses, there were intervention effects for HOA and aMCI groups in strategy knowledge (HOA: η 2 = 0.20; aMCI: η 2 = 0.06), strategy use (HOA: η 2 = 0.18; aMCI: η 2 = 0.08), and wellbeing (HOA: η 2 = 0.11; aMCI: η 2 = 0.05). There were also intervention effects in the HOA group, but not the aMCI group, in self-reported memory ability (η 2 = 0.06) and prospective memory tests (η 2 = 0.02). By six-month follow-up, gains were found on most HOA outcomes. In the aMCI group gains were found in strategy use, and by this stage, gains in prospective memory were also found. Conclusion: Memory groups can engage older people in techniques for maintaining cognitive health and improve memory performance, but more modest benefits are seen for older adults with aMCI. Show more

Keywords: Aging, memory, memory training, mild cognitive impairment, prospective memory, randomized controlled trial

DOI: 10.3233/JAD-150378

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 31-43, 2016

Authors: Triplett, Judy C. | Swomley, Aaron M. | Cai, Jian | Klein, Jon B. | Butterfield, D. Allan

Article Type: Research Article

Abstract: Alzheimer’s disease (AD), the most common age-related neurodegenerative disorder, is clinically characterized by progressive neuronal loss resulting in loss of memory and dementia. AD is histopathologically characterized by the extensive distribution of senile plaques and neurofibrillary tangles, and synapse loss. Amnestic mild cognitive impairment (MCI) is generally accepted to be an early stage of AD. MCI subjects have pathology and symptoms that fall on the scale intermediately between ‘normal’ cognition with little or no pathology and AD. A rare number of individuals, who exhibit normal cognition on psychometric tests but whose brains show widespread postmortem AD pathology, are classified as …‘asymptomatic’ or ‘preclinical’ AD (PCAD). In this study, we evaluated changes in protein phosphorylation states in the inferior parietal lobule of subjects with AD, MCI, PCAD, and control brain using a 2-D PAGE proteomics approach in conjunction with Pro-Q Diamond phosphoprotein staining. Statistically significant changes in phosphorylation levels were found in 19 proteins involved in energy metabolism, neuronal plasticity, signal transduction, and oxidative stress response. Changes in the disease state phosphoproteome may provide insights into underlying mechanisms for the preservation of memory with expansive AD pathology in PCAD and the progressive memory loss in amnestic MCI that escalates to the dementia and the characteristic pathology of AD brain. Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, neurodegeneration, phosphoproteomics, phosphorylation, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-150417

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 45-62, 2016

Authors: Sun, Xuying | Ma, Ronghong | Yao, Xiuqing | Shang, Xiaoling | Wang, Qun | Wang, Jian-Zhi | Liu, Gongping

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) seriously threatens patients’ lives and causes severe burden to the families. Early prevention and treatment can alleviate the development of the disease; therefore it is important to find new effective and non-traumatic biomarkers for early diagnosis. In this study, peripheral blood samples were collected from 24 AD patients and the same number of age- and gender-matched control subjects. Lectin reactive glycosylation levels including beta-D-galactosyl ricinus communis agglutinin 120 (RCA), peanut agglutinin (PNA), concanavalin agglutinin (Con A), alpha-L-fucosyl ulex europeus agglutinin (UEA), dolichos biflorus agglutinin (DBA), and galanthus nivalis (GNL), in the red blood cells of peripheral blood …were examined by western blotting. We found that lectin levels were altered with aging and gender; some lectin levels were different between AD patients and the control subjects. Only Con A levels were significantly decreased in AD patients compared to age-matched control subjects. These results suggest that Con A levels in peripheral blood may be a potent diagnostic marker for AD. Show more

Keywords: Alzheimer’s disease, Con A, glycoproteins, lectin, peripheral blood

DOI: 10.3233/JAD-150539

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 63-72, 2016

Authors: Salmerón, Sergio | Huedo, Isabel | López-Utiel, Melisa | Soler-Moratalla, Isabel | Flores-Ruano, Teresa | Fernández-Sánchez, Miguel | Noguerón, Alicia | Doody, Rachelle S. | Abizanda, Pedro

Article Type: Research Article

Abstract: Background: There are no short valid instruments to evaluate cognitive status in severe Alzheimer’s disease (AD) patients in the Spanish language. Objective: To validate the Spanish version of the Baylor Profound Mental Status Examination (BPMSE-Sp). Methods: The Baylor Profound Mental Status Examination (BPMSE) was translated to Spanish and back translated. Validation was conducted in 100 patients with severe probable AD with a Mini-Mental State Examination (MMSE) <12. We assessed internal consistency (Cronbach’s alpha), concurrent validity (Pearson’s correlations) with the MMSE, Severe Impairment Battery (SIB), Neuropsychiatric Inventory Short Form (NPI-Q) and the Functional Assessment Staging and reliability. …Results: The mean age of patients was 84.9; 74% were female; 64% were institutionalized. The mean MMSE was 5.6; the mean BPMSE-Sp was 13.6; the mean BPMSE-Sp behavior was 1.2; the mean SIB was 42.2; and the mean NPI-Q was 4.7. BPMSE-Sp presented good internal consistency (Cronbach α = 0.84). There were significant correlations between the BPMSE-Sp and MMSE (r  = 0.86, p  <  0.001), and between the BPMSE-Sp and SIB (r  = 0.92, p  <  0.001). Inter-rater and test-retest reliability were in both cases excellent, ranging between 0.96 and 0.99 (p  <  0.001). BPMSE-Sp had fewer floor and ceiling effects than the MMSE. Conclusions: The BPMSE-Sp is a valid tool for use in daily practice and research in the evaluation of cognitive function of patients with severe AD. Show more

Keywords: Alzheimer’s disease, Baylor Profound Mental Status Examination, severe dementia, validation

DOI: 10.3233/JAD-150422

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 73-78, 2016

Authors: Einarsdottir, Anna Bryndis | Hardarson, Sveinn Hakon | Kristjansdottir, Jona Valgerdur | Bragason, David Thor | Snaedal, Jon | Stefánsson, Einar

Article Type: Research Article

Abstract: Background: Structural and physiological abnormalities have been reported in the retina in Alzheimer’s disease (AD). Retinal oximetry detects changes in retinal oxygen metabolism in many eye diseases, where structural changes are seen. Objective: To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort. Methods: Oxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. 18 individuals with mild to moderate dementia of the Alzheimer-type (stage 3–5 according to the Global Deterioration Scale) and 18 healthy subjects underwent retinal oximetry in a case control …study. Results: Retinal oxygen saturation in arterioles and venules in patients with moderate AD was significantly elevated compared to healthy individuals. Retinal arterioles have 94.2 ± 5.4% oxygen saturation in moderate AD compared with 90.5 ± 3.1% in healthy subjects (mean ± SD, n  = 10, p  = 0.028). Retinal venules were 51.9 ± 6.0% saturated in moderate AD compared with 49.7 ± 7.0% in healthy subjects (mean ± SD, n  = 10, p  = 0.02). Conclusion: This is the first study of retinal oxygen metabolism in any central nervous system disease. It discovers abnormalities in retinal oxygen metabolism in AD. The findings are similar to those seen in age-related macular degeneration and diabetic retinopathy. Noninvasive retinal oximetry may offer new insights into pathophysiology of AD. Further studies are needed to confirm and expand these findings. Show more

Keywords: Alzheimer’s disease, blood vessels, diagnosis, hemoglobin, oxygen, retina, retinal oximetry, vessel diameter

DOI: 10.3233/JAD-150457

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 79-83, 2016

Authors: Yoon, Bora | Shim, Yong S. | Park, Hee-Kyung | Park, Sun Ah | Choi, Seong Hye | Yang, Dong Won

Article Type: Research Article

Abstract: Background: Only a few studies have investigated disease progression in patients with early-onset Alzheimer’s disease (EOAD). Therefore, the aim of this study was to investigate disease progression in patients with EOAD and the influence of various factors, such as gender, education, and apolipoprotein E (APOE) genotype on disease progression. Methods: A total of 288 EOAD patients were enrolled in the study. Linear mixed models were used to investigate the rate of cognitive and functional decline in terms of age at onset, gender, education, follow-up period, and APOE genotype. Results: EOAD patients showed an annual decline of …–1.54 points/years in the Korean version mini-mental examination score, an annual increase of 3.46 points/year in the Seoul instrumental activities of daily living (SIADL) score, and an annual increase of 1.15 points/year in the clinical dementia rating scale-sum of boxes score. After stratification, higher educated patients showed faster disease progression in all three parameters, and female patients demonstrated faster disease progression as assessed by the SIADL score. Age at onset and APOE genotype had no influence on disease progression. Conclusion: We confirmed the rate of disease progression in Korean patients with EOAD in real-life hospital-based clinical practice. The results of this study suggest that education and female gender, not APOE genotype, may be important as independent strong predictive factors for disease progression in patients with EOAD. Show more

Keywords: Alzheimer’s disease, cognitive reserve, disease progression, early-onset, education, longitudinal study

DOI: 10.3233/JAD-150462

Citation: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 85-91, 2016