Journal of Alzheimer's Disease - Volume 55, issue 3

Authors: Nemeth, Viola Luca | Must, Anita | Horvath, Szatmar | Király, Andras | Kincses, Zsigmond Tamas | Vécsei, László

Article Type: Review Article

Abstract: Age-related changes in brain structure are a question of interest to a broad field of research. Structural decline has been consistently, but not unambiguously, linked to functional consequences, including cognitive impairment and dementia. One of the areas considered of crucial importance throughout this process is the medial temporal lobe, and primarily the hippocampal region. Gender also has a considerable effect on volume deterioration of subcortical grey matter (GM) structures, such as the hippocampus. The influence of age×gender interaction on disproportionate GM volume changes might be mediated by hormonal effects on the brain. Hippocampal volume loss appears to become accelerated in …the postmenopausal period. This decline might have significant influences on neuroplasticity in the CA1 region of the hippocampus highly vulnerable to pathological influences. Additionally, menopause has been associated with critical pathobiochemical changes involved in neurodegeneration. The micro- and macrostructural alterations and consequent functional deterioration of critical hippocampal regions might result in clinical cognitive impairment–especially if there already is a decline in the cognitive reserve capacity. Several lines of potential vulnerability factors appear to interact in the menopausal period eventually leading to cognitive decline, mild cognitive impairment, or Alzheimer’s disease. This focused review aims to delineate the influence of unmodifiable risk factors of neurodegenerative processes, i.e., age and gender, on critical subcortical GM structures in the light of brain derived estrogen effects. The menopausal period appears to be of key importance for the risk of cognitive decline representing a time of special vulnerability for molecular, structural, and functional influences and offering only a narrow window for potential protective effects. Show more

Keywords: Aging, cognitive decline, gender, hippocampus CA1 region, subcortical grey matter

DOI: 10.3233/JAD-160812

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 865-880, 2017

Authors: Serino, Silvia | Riva, Giuseppe

Article Type: Research Article

Abstract: In addition to impairments in episodic and spatial memory, anosognosia (i.e., loss of awareness of the deficient aspect of own cognitive functioning) may be considered an important cognitive marker of Alzheimer’s disease (AD). However, although a growing body of interesting models have been proposed to explain this early symptom, what is still missing is a unifying framework of all the characteristic signs occurring in patients with AD that may guide the search for its causal neuropathological process and, ultimately, the etiological process. This contribution will first show how anosognosia may be related to the above-mentioned episodic and spatial memory impairment …through a unifying framework of all these characteristic signs, i.e., the continuous interaction between different spatial representations. Second, we hypothesize that a break in the interaction between different spatial representations, as we suggest occurs in AD, may contribute significantly both to the early impairments in spatial and episodic memory, and to a deficient self-awareness since it may interfere with the capacity of the brain to detect predictive errors. Show more

Keywords: Allocentric reference frame, Alzheimer’s disease, anosognosia, egocentric reference frame, episodic memory

DOI: 10.3233/JAD-160676

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 881-892, 2017

Authors: Wolters, Frank J. | Bos, Daniel | Vernooij, Meike W. | Franco, Oscar H. | The Heart-Brain Connection collaborative research group | Hofman, Albert | Koudstaal, Peter J. | van der Lugt, Aad | Ikram, M. Arfan

Article Type: Short Communication

Abstract: The association of aortic valve calcification (AVC) with dementia remains unknown. In 2,428 non-demented participants from the population-based Rotterdam Study, we investigated the association of CT-assessed AVC with risk of dementia and cognitive decline. AVC was present in 33.1% of the population. During a median follow-up of 9.3 years, 160 participants developed dementia. We found no association between presence of AVC and risk of all-cause dementia [hazard ratio (HR): 0.89 (95% confidence interval (CI):0.63;1.26)]. Presence of AVC was not associated with cognitive decline on any of the cognitive tests, nor with a measure of global cognition.

Keywords: Aortic valve pathology, calcification, dementia, epidemiology, imaging

DOI: 10.3233/JAD-160871

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 893-897, 2017

Authors: de la Rubia Ortí, Jose Enrique | Sancho Castillo, Sandra | Benlloch, Maria | Julián Rochina, Mariano | Corchón Arreche, Silvia | García-Pardo, María Pilar

Article Type: Short Communication

Abstract: The understanding of how the immune system works, as well as its relationship with the stress level, seems to be important at the start of the Alzheimer’s disease (AD). To analyze this, immunoglobulin A (IgA) and cortisol in saliva were measured using ELISA in patients with mild AD and healthy volunteers, and the production of both biomarkers was compared and correlated. In participants without AD, IgA was higher when cortisol was lower, and the opposite happened in participants with AD, with the quantification in saliva being a suitable method to determine it.

Keywords: Alzheimer’s disease, cortisol, immune system, immunoglobulin A, stress

DOI: 10.3233/JAD-160903

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 899-903, 2017

Authors: Noguchi-Shinohara, Moeko | Komatsu, Junji | Samuraki, Miharu | Matsunari, Ichiro | Ikeda, Tokuhei | Sakai, Kenji | Hamaguchi, Tsuyoshi | Ono, Kenjiro | Nakamura, Hiroyuki | Yamada, Masahito

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) commonly accompanies cerebral amyloid angiopathy (CAA). Objective: We aimed to reveal associations between CAA-related brain microbleeds and cerebrospinal fluid (CSF) markers in AD patients. Methods: Patients with probable AD (n  = 88) from consecutive patients in our memory clinic were evaluated for patient demographics, vascular risk factors, neuropsychological tests, apolipoprotein E phenotype, MRI including T2*-weighted image and fluid attenuated inversion recovery sequence, and CSF amyloid and tau markers. Results: The 88 patients with AD included 15 with microbleeds only in cortical/subcortical regions (cortical microbleeds) that could be CAA-related, 16 with …microbleeds only in deep locations (deep microbleeds), 3 with microbleeds in both cortical and deep locations (mixed microbleeds), and 54 without microbleeds. The CSF levels of amyloid β-protein 1–40 (Aβ40 ) and amyloid β-protein 1–42 (Aβ42 ) were significantly lower in patients with cortical microbleeds than in those without microbleeds (p  = 0.001 and p  = 0.027, respectively). The result remained unchanged after adjustment for age, sex, apolipoprotein E E4 presence, and leukoaraiosis. Conclusions: CAA-related cortical microbleeds would be associated with lower CSF levels of Aβ40 and Aβ42 in AD, reflecting the deposition of both Aβ40 and Aβ42 in the cerebrovasculature. Show more

Keywords: Alzheimer’s disease, biomarkers, cerebral amyloid angiopathy, cerebrospinal fluid

DOI: 10.3233/JAD-160651

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 905-913, 2017

Authors: Martins, Isaura V.A. | Rivers-Auty, Jack | Allan, Stuart M. | Lawrence, Catherine B.

Article Type: Research Article

Abstract: Obesity is associated with impaired memory in humans, and obesity induced by high-fat diets leads to cognitive deficits in rodents and in mouse models of Alzheimer’s disease (AD). However, it remains unclear how high-fat diets contribute to memory impairment. Therefore, we tested the effect of a high-fat diet on memory in male and female control non-transgenic (Non-Tg) and triple-transgenic AD (3xTgAD) mice and determined if a high-fat diet caused similar ultrastructural abnormalities to those observed in AD. Behavior was assessed in mice on control or high-fat diet at 4, 8, or 14 months of age and ultrastructural analysis at 8 months of …age. A high-fat diet increased body weight, fat weight, and insulin levels with some differences in these metabolic responses observed between Non-Tg and 3xTgAD mice. In both sexes, high-fat feeding caused memory impairments in Non-Tg mice and accelerated memory deficits in 3xTgAD mice. In 3xTgAD mice, changes in hippocampal mitochondrial morphology were observed in capillaries and brain neuropil that were accompanied by a reduction in synapse number. A high-fat diet also caused mitochondria abnormalities and a reduction in synapse number in Non-Tg mice, but did not exacerbate the changes seen in 3xTgAD mice. Our data demonstrate that a high-fat diet affected memory in Non-Tg mice and produced similar impairments in mitochondrial morphology and synapse number comparable to those seen in AD mice, suggesting that the detrimental effects of a high-fat diet on memory might be due to changes in mitochondrial morphology leading to a reduction in synaptic number. Show more

Keywords: 3xTgAD, Alzheimer’s disease, high-fat diet, memory, mitochondria, Non-Tg, obesity, synapses

DOI: 10.3233/JAD-160640

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 915-932, 2017

Authors: Golden, Hannah L. | Clark, Camilla N. | Nicholas, Jennifer M. | Cohen, Miriam H. | Slattery, Catherine F. | Paterson, Ross W. | Foulkes, Alexander J.M. | Schott, Jonathan M. | Mummery, Catherine J. | Crutch, Sebastian J. | Warren, Jason D.

Article Type: Research Article

Abstract: Despite much recent interest in music and dementia, music perception has not been widely studied across dementia syndromes using an information processing approach. Here we addressed this issue in a cohort of 30 patients representing major dementia syndromes of typical Alzheimer’s disease (AD, n  = 16), logopenic aphasia (LPA, an Alzheimer variant syndrome; n  = 5), and progressive nonfluent aphasia (PNFA; n  = 9) in relation to 19 healthy age-matched individuals. We designed a novel neuropsychological battery to assess perception of musical patterns in the dimensions of pitch and temporal information (requiring detection of notes that deviated from the established pattern based on …local or global sequence features) and musical scene analysis (requiring detection of a familiar tune within polyphonic harmony). Performance on these tests was referenced to generic auditory (timbral) deviance detection and recognition of familiar tunes and adjusted for general auditory working memory performance. Relative to healthy controls, patients with AD and LPA had group-level deficits of global pitch (melody contour) processing while patients with PNFA as a group had deficits of local (interval) as well as global pitch processing. There was substantial individual variation within syndromic groups. Taking working memory performance into account, no specific deficits of musical temporal processing, timbre processing, musical scene analysis, or tune recognition were identified. The findings suggest that particular aspects of music perception such as pitch pattern analysis may open a window on the processing of information streams in major dementia syndromes. The potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants further systematic investigation. Show more

Keywords: Alzheimer’s disease, auditory scene analysis, dementia, logopenic aphasia, music, progressive nonfluent aphasia

DOI: 10.3233/JAD-160359

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 933-949, 2017

Authors: Pařízková, Martina | Andel, Ross | Lerch, Ondřej | Marková, Hana | Gažová, Ivana | Vyhnálek, Martin | Hort, Jakub | Laczó, Jan

Article Type: Research Article

Abstract: Background: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer’s disease (AD) and lower cognitive performance in older adults. Objective: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. Methods: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, …neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. Results: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (β= 0.31; p  = 0.003 and β= 0.23; p  = 0.017) but not allocentric (p  > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. Conclusion: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults. Show more

Keywords: Alzheimer’s disease, APOE, homocysteine, mild cognitive impairment, spatial navigation, subjective cognitive decline, vascular factors

DOI: 10.3233/JAD-160667

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 951-964, 2017

Authors: Beauchet, Olivier | Launay, Cyrille P. | Chabot, Julia | Levinoff, Elise J. | Allali, Gilles

Article Type: Research Article

Abstract: Background: Increased stride time variability has been associated with memory impairment in mild cognitive impairment. Subjective memory impairment (SMI) is considered the earliest clinical stage of Alzheimer’s disease (AD). The association between increased stride time variability and SMI has not been reported. Objective: This study aims to examine the association of stride time variability while performing single and dual tasking with SMI in cognitively healthy individuals (CHI). Methods: A total of 126 CHI (15 without SMI, 69 with SMI expressed by participants, 10 with SMI expressed by participant’s relative, and 32 with SMI expressed by …both participants and their relatives) were included in this cross-sectional study. The coefficient of variation (CoV) of stride time and walking speed were recorded under usual condition and while counting backwards. Age, gender, body mass index, number of drugs taken daily, use of psychoactive drugs, fear of falling, history of previous falls, and walking speed were used as covariates. Results: The multiple linear regression models showed that greater CoV of stride time while counting backwards, but not while single tasking, was associated with a participant’s relative SMI (p  = 0.038). Conclusion: This study found a specific association between SMI expressed by a participant’s relative and a greater CoV of stride time (i.e., worse performance) while dual tasking, suggesting that the association between gait variability and memory may be present in the earliest stages of memory impairment. Thus, gait variability under dual-task in individuals with SMI expressed by their relatives can be a potential biomarker of AD. Show more

Keywords: Dementia, dual tasking, gait variability, motor control, subjective memory impairment

DOI: 10.3233/JAD-160604

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 965-971, 2017

Authors: Papazacharias, Apostolos | Lozupone, Madia | Barulli, Maria Rosaria | Capozzo, Rosa | Imbimbo, Bruno P. | Veneziani, Federica | De Blasi, Roberto | Nardini, Marcello | Seripa, Davide | Panza, Francesco | Logroscino, Giancarlo

Article Type: Research Article

Abstract: Bipolar disorder (BD) could represent a prodromal state of frontotemporal dementia (FTD). Two patients affected by lifelong BD with a progressive decline of cognitive functions, behavioral, and neurological signs, reached the early diagnosis of FTD before the age of 60. They were diagnosed as affected by primary progressive aphasia and FTD with parkinsonism, respectively. A diagnosis of FTD should therefore be taken into account, in case of unexpected cognitive and behavioral decline in patients with a long history of BD. Follow-up studies with genetic, neuropsychological, and neuroimaging markers of these BD/FTD patients could further explore some of the underlying association, opening new viable therapeutic …options. Show more

Keywords: Bipolar disorder, behavioral decline, cognitive impairment, frontotemporal dementia, parkinsonism, primary progressive aphasia

DOI: 10.3233/JAD-160860

Citation: Journal of Alzheimer's Disease, vol. 55, no. 3, pp. 973-979, 2017