Journal of Alzheimer's Disease - Volume 53, issue 4

Authors: Camargo, Erica C. | Weinstein, Galit | Beiser, Alexa S. | Tan, Zaldy S. | DeCarli, Charles | Kelly-Hayes, Margaret | Kase, Carlos | Murabito, Joanne M. | Seshadri, Sudha

Article Type: Research Article

Abstract: Background: Handgrip strength and gait speed are simple measures of physical capability and have been associated with current and future health outcomes. However, studies on their associations with brain structure and function in middle-aged adults are lacking. Objective: To assess the relationship of fast-paced walking speed and handgrip strength with risk of dementia, Alzheimer’s disease (AD), and stroke, as well as the cross-sectional associations with cognitive and brain magnetic resonance imaging (MRI) measures in a middle-aged community sample. Methods: Framingham Offspring (n  = 2,176; mean age 62, 54% female) had physical function, brain MRI, and cognitive …evaluations between 1999 and 2005 and were followed-up for incident dementia AD and stroke until 11 years later. We related walking speed and handgrip strength to incident dementia, AD, and stroke using Cox models, and to brain and cognitive measures using multivariable linear and logistic regression. Models were adjusted for age, sex, education, and vascular risk factors. Results: Slow walking and weak handgrip were associated with more than 2.5-fold increase in risk of AD. Weaker handgrip was associated with an increased risk of incident stroke (HR 1.74, 95% CI: 1.12–2.70/SDU, p  = 0.01) in persons ≥65 years. Both measures were associated with lower total brain volume and poorer performance on tests of visual memory, language, executive function, and visuoperceptual function. Slower gait was also related to poorer verbal memory, and weaker handgrip to poorer abstraction. Conclusion: Tests of walking speed and handgrip strength may serve as clinical markers of brain structure and function and may improve dementia risk prediction. Show more

Keywords: Alzheimer’s disease, brain imaging, cognitive function, dementia, gait, hand strength, observational study, stroke

DOI: 10.3233/JAD-160229

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1597-1608, 2016

Authors: Krell-Roesch, Janina | Ruider, Hanna | Lowe, Val J. | Stokin, Gorazd B. | Pink, Anna | Roberts, Rosebud O. | Mielke, Michelle M. | Knopman, David S. | Christianson, Teresa J. | Machulda, Mary M. | Jack, Clifford R. | Petersen, Ronald C. | Geda, Yonas E.

Article Type: Research Article

Abstract: One of the key research agenda of the field of aging is investigation of presymptomatic Alzheimer’s disease (AD). Furthermore, abnormalities in brain glucose metabolism (as measured by FDG-PET) have been reported among cognitively normal elderly persons. However, little is known about the association of FDG-PET abnormalities with neuropsychiatric symptoms (NPS) in a population-based setting. Thus, we conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging in order to examine the association between brain glucose metabolism and NPS among cognitively normal (CN) persons aged > 70 years. Participants underwent FDG-PET and completed the Neuropsychiatric Inventory Questionnaire (NPI-Q), Beck …Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Cognitive classification was made by an expert consensus panel. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals after adjusting for age, sex, and education. For continuous variables, we used linear regression and Spearman rank-order correlations. Of 668 CN participants (median 78.1 years, 55.4% males), 205 had an abnormal FDG-PET (i.e., standardized uptake value ratio < 1.32 in AD-related regions). Abnormal FDG-PET was associated with depression as measured by NPI-Q (OR = 2.12; 1.23–3.64); the point estimate was further elevated for APOE ɛ 4 carriers (OR = 2.59; 1.00–6.69), though marginally significant. Additionally, we observed a significant association between abnormal FDG-PET and depressive and anxiety symptoms when treated as continuous measures. These findings indicate that NPS, even in community-based samples, can be an important additional tool to the biomarker-based investigation of presymptomatic AD. Show more

Keywords: Agitation, Alzheimer’s disease, anxiety, apathy, cognitively normal persons, depression, FDG-PET, neuroimaging, neuropsychiatric symptoms

DOI: 10.3233/JAD-160326

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1609-1616, 2016

Authors: Jakobsen, Jannik E. | Johansen, Marianne G. | Schmidt, Mette | Liu, Ying | Li, Rong | Callesen, Henrik | Melnikova, Margarita | Habekost, Mette | Matrone, Carmela | Bouter, Yvonne | Bayer, Thomas A. | Nielsen, Anders Lade | Duthie, Monika | Fraser, Paul E. | Holm, Ida E. | Jørgensen, Arne Lund

Article Type: Research Article

Abstract: Mutations in the amyloid-β protein precursor gene (AβPP ), the presenilin 1 gene (PSEN1 ) or the presenilin 2 gene (PSEN2 ) that increase production of the AβPP-derived peptide Aβ42 cause early-onset Alzheimer’s disease. Rodent models of the disease show that further increase in Aβ42 production and earlier brain pathology can be obtained by coexpressing AβPP and PSEN1 mutations. To generate such elevated Aβ42 level in a large animal model, we produced Göttingen minipigs carrying in their genome one copy of a human PSEN1 cDNA with the Met146Ile (PSEN1M146I ) mutation and three copies …of a human AβPP695 cDNA with the Lys670Asn/Met671Leu (AβPPsw ) double-mutation. Both transgenes were expressed in fibroblasts and in the brain, and their respective proteins were processed normally. Immunohistochemical staining with Aβ42 -specific antibodies detected intraneuronal accumulation of Aβ42 in brains from a 10- and an 18-month-old pig. Such accumulation may represent an early event in the pathogenesis of Alzheimer’s disease. Show more

Keywords: Alzheimer’s disease, amyloid, porcine model, presenilin, transgenic

DOI: 10.3233/JAD-160408

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1617-1630, 2016

Authors: Venturelli, Massimo | Sollima, Alessio | Cè, Emiliano | Limonta, Eloisa | Bisconti, Angela V. | Brasioli, Anna | Muti, Ettore | Esposito, Fabio

Article Type: Research Article

Abstract: Sundowning syndrome (SDS) in patients with Alzheimer’s disease (AD) is characterized by the intensification of behavioral disorders at sunset. Despite SDS etiology being unclear, a strong relationship between high cortisol levels and SDS has been reported. Aerobic exercise (AE) and cognitive training (CT) can reduce cortisol levels. However, whether SDS would benefit from AE and CT is still unknown. Therefore, the aim of this study was to investigate whether AE and CT treatments are effective in reducing SDS via downregulation of cortisol levels. The possible additive effects of combined AE+CT were also assessed. Eighty AD patients were randomly assigned to …AE (n  = 20), CT (n  = 20), AE+CT (n  = 20), and standard therapy (no treatment, NT; n  = 20). Treatments were administered for 3 months, 5 days/week, 1 hour before sunset. Before and after treatments, salivary cortisol levels were sampled at 7, 11, 15, at sunset, and 20 (time of day). Blind assessment of behavioral disorders (neuropsychiatric inventory, NPI) and agitation (agitated behavior scale, ABS) were also performed. After interventions, cortisol levels were reduced in AE and AE+CT by ∼26%. In the same groups, NPI and ABS decreased by ∼50%. By contrast, cortisol and behavioral disorders were similar to baseline in CT and NT. Changes in NPI and ABS were significantly correlated with the reduction in cortisol levels. AE or AE+CT effects on SDS and cortisol levels and the lack of effect of CT alone indicate the effectiveness of an exercise-based treatment on SDS, suggesting a possible hypothalamic–pituitary–adrenal axis dysregulation underpinning SDS. Show more

Keywords: Alzheimer’s disease, behavioral disorders, cortisol, exercise

DOI: 10.3233/JAD-160392

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1631-1640, 2016

Authors: Malek-Ahmadi, Michael | Perez, Sylvia E. | Chen, Kewei | Mufson, Elliott J.

Article Type: Research Article

Abstract: The presence of Alzheimer’s disease (AD)-related neuropathology among cognitively normal individuals has been well documented. It has been proposed that these individuals may represent a pre-clinical AD population. Previous studies have demonstrated a negative association between the presence of both amyloid-β (Aβ) plaques and neurofibrillary tangles with ante-mortem cognitive performance, a relationship which is likely influenced by a number of factors including age and APOE ɛ 4 carrier status. The present study determined whether the presence of neuritic plaques (NPs) and diffuse plaques (DPs) are associated with performance in a number of cognitive domains after accounting for APOE ɛ 4 …carrier status and neurofibrillary tangle presence in a cohort of 123 older participants from the Rush Religious Order Study who died with a premortem clinical diagnosis of no cognitive impairment (NCI). After adjusting for age at death, education, gender, Braak stage, and APOE ɛ 4 carrier status, the presence of NPs was associated with lower performance in the cognitive domains of Global Cognition (p  = 0.002), Episodic Memory (p  = 0.03), Semantic Memory (p  = 0.009), and Visuospatial performance (p  = 0.006), while DPs showed no association with any cognitive domain examined. These results suggest that decreases in cognition in elderly NCI individuals are associated with an increase in NPs and not DPs when age at death, education, gender, APOE ɛ 4 status, and Braak stage are taken into consideration. Show more

Keywords: Amyloid-β, Braak stage, cognition, neuropathology, pre-clinical Alzheimer’s disease

DOI: 10.3233/JAD-160365

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1641-1652, 2016

Article Type: Other

DOI: 10.3233/JAD-160628

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1653-1657, 2016

Article Type: Other

Citation: Journal of Alzheimer's Disease, vol. 53, no. 4, pp. 1659-1675, 2016