Journal of Alzheimer's Disease - Volume 32, issue 4

Authors: Escudero, Javier | Ifeachor, Emmanuel | Zajicek, John P. | for the Alzheimer's Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: This article presents a new approach for the analysis of biomedical data to support the management and care of patients with Alzheimer's disease (AD). The increase in prevalence of neurodegenerative disorders such as AD has led to a need for objective means to assist clinicians with the analysis and interpretation of complex biomedical data. To this end, we propose a “Bioprofile” analysis to reveal the pattern of disease in the subject's biodata. From the Bioprofile, personal “Bioindices” that indicate how closely a subject's data resemble the pattern of AD can be derived. We used an unsupervised technique (k-means) to cluster …variables of the ADNI database so that subjects are divisible into those with the Bioprofile of AD and those without it. Results revealed that there is an “AD pattern” in the biodata of most AD and mild cognitive impairment (MCI) patients and some controls. This pattern agrees with a recent hypothetical model of AD evolution. We also assessed how the Bioindices changed with time and we found that the Bioprofile was associated with the risk of progressing from MCI to AD. Hence, the Bioprofile analysis is a promising methodology that may potentially provide a complementary new way of interpreting biomedical data. Furthermore, the concept of the Bioprofile could be extended to other neurodegenerative diseases. Show more

Keywords: Alzheimer's disease, Bioindex, biomarkers, Bioprofile, machine learning, mild cognitive impairment, unsupervised techniques

DOI: 10.3233/JAD-2012-121024

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 997-1010, 2012

Authors: Segal, Sabrina K. | Cotman, Carl W. | Cahill, Lawrence F.

Article Type: Research Article

Abstract: Post-trial pharmacological activation of the noradrenergic system can facilitate memory consolidation. Because exercise activates the locus coeruleus and increases brain norepinephrine release, we hypothesized that post-trial exercise could function as a natural stimulus to enhance memory consolidation. We investigated this in amnestic mild cognitive impairment (aMCI) and cognitively normal elderly individuals by examining the effects of an acute bout of post-learning, aerobic exercise (6 minutes at 70% VO2 max on a stationary bicycle) on memory for some emotional images. Exercise significantly elevated endogenous norepinephrine (measured via the biomarker, salivary alpha-amylase) in both aMCI patients and controls. Additionally, exercise retrogradely …enhanced memory in both aMCI patients and controls. Acute exercise that activates the noradrenergic system may serve as a beneficial, natural, and practical therapeutic intervention for cognitive decline in the aging population. Show more

Keywords: Cognition, exercise, memory, noradrenaline, noradrenergic

DOI: 10.3233/JAD-2012-121078

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1011-1018, 2012

Authors: Zhao, Qianhua | Xiong, Yunyun | Ding, Ding | Guo, Qihao | Hong, Zhen

Article Type: Research Article

Abstract: Diabetes is thought to contribute to cognitive impairment in the elderly. The risk may be modified by genetic factors such as apolipoprotein E (APOE). We aim to determine the prevalence of dementia in Chinese diabetics and non-diabetic individuals, and assess the effect of the APOE genotype. A cross-sectional study was conducted among participants aged 50 and over in an urban community. Subjects were 1 : 1 matched for age and gender (diabetes group (n = 497) versus non-diabetes group (n = 497)). Each subject was interviewed for dementia and related risk factors. Fasting blood samples were drawn for glucose and …APOE. Subjects were screened using the Mini Mental State Examination (MMSE) and were examined by a series of neuropsychological tests if screened positive (indicated by an MMSE score below 19, 21, and 24, respectively according to different educational attainment). A diagnosis of dementia was defined according to DSM-IV criteria. The prevalence of all-cause dementia, Alzheimer's disease, and vascular dementia in diabetics (4.8%, 2.7%, 1.4%) was higher than that of non-diabetics (2.2%, 1.2%, 0.4%) (all-cause dementia, diabetics versus non-diabetics, p < 0.05). APOE ε4 carriers had higher prevalence of dementia and AD (diabetics: 9.2%, 7.55%, non-diabetics: 3.3%, 3.3%) than APOE ε4 non-carriers (diabetics: 6.3%, 2.3%, non-diabetics: 2.35%, 0.7%) (p < 0.05). Diabetics carrying the APOE ε4 allele had a 3.982-fold [95%CI, 1.418–11.184] likelihood of having dementia compared with those without these two factors. This study showed that the prevalence of dementia was significantly higher in diabetics than non-diabetics. APOE ε4 further enhanced the risk. Show more

Keywords: Alzheimer's disease, apolipoprotein E, dementia, diabetes

DOI: 10.3233/JAD-2012-120442

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1019-1027, 2012

Authors: Head, Elizabeth | Murphey, Heather L. | Dowling, Amy L.S. | McCarty, Katie L. | Bethel, Samuel R. | Nitz, Jonathan A. | Pleiss, Melanie | Vanrooyen, Jenna | Grossheim, Mike | Smiley, Jeffery R. | Murphy, M. Paul | Beckett, Tina L. | Pagani, Dieter | Bresch, Frederick | Hendrix, Curt

Article Type: Research Article

Abstract: Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of amyloid-β (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Thus, 9 aged beagles (98–115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) …an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11) = 4.3, p = 0.001) and were more accurate across all distances (F(1,9) = 20.7, p = 0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and cerebrospinal fluid Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. Show more

Keywords: Alzheimer's disease, amyloid-β, cognition, dog, inflammation, oxidative damage, spatial attention

DOI: 10.3233/JAD-2012-120937

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1029-1042, 2012

Authors: Choi, Seong Hye | Olabarrieta, Mikel | Lopez, Oscar L. | Maruca, Victoria | DeKosky, Steven T. | Hamilton, Ronald L. | Becker, James T. | for the Alzheimer's Disease Research Center

Article Type: Research Article

Abstract: Up to 60% of the patients with Alzheimer's disease (AD) can have cortical or brainstem Lewy bodies (LB), and extrapyramidal signs (EPS) have been found to be associated with LB in AD patients. However, the relationship between EPS and brain volumes has not been studied in the LB variant of AD using structural magnetic resonance imaging (MRI). The purpose of this study was to determine the relationship between patterns of brain atrophy and clinical EPS in patients with pathologically confirmed AD. We compared gray matter structure using voxel-based morphometry in 29 Definite AD cases, 16 (55%) of whom also had …LBs identified with α-synuclein immunohistochemistry. Multivariate models analyzed brain volume at a voxel level accounting for subject group, Mini-Mental State Examination (MMSE), EPS, total brain volume, and the time from MRI scan to death. There was no significant difference in gray matter volume in the Definite AD patients as a function of LB. There was a significant association between gray matter volumes and the MMSE in AD patients, both with and without LBs. There was a significant correlation between gray matter volume and EPS only in the group of AD patients with LBs, and not in those with pure AD. These findings suggest that that the etiology of EPS in patients with the LB variant of AD is associated with neuronal loss in the nigrostriatal tracts. By contrast, the source of the EPS in AD alone appears to be less well localized. Show more

Keywords: Alzheimer's disease, extrapyramidal signs, imaging, Lewy bodies, magnetic resonance imaging, voxel-based morphometry

DOI: 10.3233/JAD-2012-121108

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1043-1049, 2012

Authors: Leyton, Cristian E. | Piguet, Olivier | Savage, Sharon | Burrell, James | Hodges, John R.

Article Type: Research Article

Abstract: Logopenic progressive aphasia (LPA) is defined clinically by impairments of naming and sentence repetition. The relationship between these impairments and their neural basis has, however, not yet been determined. We aimed to localize cortical thinning associated with naming and repetition deficits using cortical thickness measurements. Consecutive LPA cases (n = 15) were matched with healthy controls (n = 16). All LPA cases underwent general cognitive testing and language assessment using the Progressive Aphasia Language Scale. Word retrieval and verbal short-term memory, the core cognitive processes involved in LPA, were assessed using visual confrontation naming and forward digit-span tasks. Cortical thickness …was estimated vertex-by-vertex using Freesurfer. The pattern of cortical thinning for the LPA group as well as the location of cortical thinning linked to the impairment of each core cognitive process was estimated using general linear models. LPA cases showed extensive left-sided cortical thinning in which the temporo-parietal junction had the greatest involvement. Impaired naming was associated with cortical thinning of the supramarginal gyrus (BA 40), while reduced digit-span score, regarded as a surrogate marker for sentence repetition, was correlated with thinning of the left superior temporal gyrus (BA 22 and 42). These results suggest that the core manifestations of LPA emerge from the damage to segregated and non-overlapping cortical regions typically affected in this focal presentation of Alzheimer's disease. Show more

Keywords: Alzheimer's disease, cortical thickness, logopenic progressive aphasia, short-term memory

DOI: 10.3233/JAD-2012-121042

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1051-1059, 2012

Article Type: Other

DOI: 10.3233/JAD-2012-32418

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1061-1069, 2012

Article Type: Other

DOI: 10.3233/JAD-2012-121043

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1071-1072, 2012

Article Type: Other

DOI: 10.3233/JAD-2012-32419

Citation: Journal of Alzheimer's Disease, vol. 32, no. 4, pp. 1073-1081, 2012