Journal of Alzheimer's Disease - Volume 64, issue 1

Authors: Saari, Toni | Hallikainen, Ilona | Hänninen, Tuomo | Räty, Hannu | Koivisto, Anne

Article Type: Research Article

Abstract: Background: Impaired cognition and activities of daily living (ADL) are core symptoms of Alzheimer’s disease (AD), but their relationship is unclear. Objectives: To explore relationships between cognitive domains and functional ability during 5-year follow-up in persons with AD. Methods: We analyzed ALSOVA study data from 236 individuals with very mild or mild AD at baseline. The CERAD Neuropsychological Battery (CERAD-NB) was used as a cognitive measure and Alzheimer’s Disease Cooperative Study ADL (ADCS-ADL) as a functional measure, analyzing the IADL and BADL sub-scores separately. Annual regression models and linear mixed-effect models (LMMs) covering a 5-year follow-up …period were used. Results: Annually, the CERAD-NB total and especially Verbal Fluency, Clock Drawing, and Constructional Praxis were associated with the total ADCS-ADL and IADL scores increasingly yet modestly, and to a lesser extent the BADL score. In the LMMs, the same measures and MMSE were associated with ADL. Conclusion: Measures of executive function and visuoconstructive skills appear to be associated with caregiver-interview based ADL measure during the progression of AD. Show more

Keywords: Activities of daily living, Alzheimer’s disease, cognition, dementia, follow-up study, functional ability

DOI: 10.3233/JAD-171059

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 269-279, 2018

Authors: Vassilaki, Maria | Aakre, Jeremiah A. | Syrjanen, Jeremy A. | Mielke, Michelle M. | Geda, Yonas E. | Kremers, Walter K. | Machulda, Mary M. | Alhurani, Rabe E. | Staubo, Sara C. | Knopman, David S. | Petersen, Ronald C. | Lowe, Val J. | Jack Jr, Clifford R. | Roberts, Rosebud O.

Article Type: Research Article

Abstract: Background: There is accumulating evidence suggesting that diet may play a role in preventing or delaying cognitive decline and dementia, but the underlying biological mechanisms are not well understood. Objectives: To examine the cross-sectional associations of the Mediterranean diet (MeDi) and its components with 11 C-PiB-PET scan measures of amyloid-β (Aβ) deposition. Methods: The study consisted of 278 Mayo Clinic Study of Aging participants 70+ years old, who were cognitively unimpaired (CU) at the time of completion of the Food Frequency Questionnaire (FFQ) and when they underwent PET imaging. Adherence to the MeDi was assessed by …computing the MeDi score for each participant. All scans were performed after the FFQ completion; median [IQR] time between FFQ and Aβ PET was 3.5 (1.4) years. Z-scores were created for component, macro- and micronutrients measured. Linear and logistic regression models were adjusted for age, sex, education, apolipoprotein E (APOE) ɛ 4 allele carrier status, time interval between the FFQ completion and PET scan, and total energy intake. Results: Participants’ median age at FFQ was 77.7 years (55.8% men; 26.6% with an APOE ɛ 4 allele). Higher MeDi score (linear regression slope (beta):–0.035, p = 0.012; per standard deviation increase), vegetable intake (beta:–0.043, p = 0.002), intake of vitamin A (beta:–0.041, p = 0.003) or β-carotene (beta: –0.039, p = 0.005) from food sources and moderate alcohol consumption (beta: –0.074, p = 0.03) were associated with lower 11 C-PiB standardized uptake value ratio. Conclusion: Findings are consistent with previous studies suggesting that higher adherence to a MeDi pattern and higher vegetable consumption are associated with better neuroimaging biomarker profile. Prospective studies are needed to validate current findings. Show more

Keywords: Amyloid, cross-sectional study, Mediterranean diet, vegetables

DOI: 10.3233/JAD-171121

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 281-290, 2018

Authors: Li, Haitao | Jia, Jianping | Wang, Wei | Hou, Tingting | Tian, , Yuanruhua | Wu, Qiaoqi | Xu, Lingzhi | Wei, Yiping | Wang, Xiu

Article Type: Research Article

Abstract: Accumulating evidence has demonstrated that mitochondrial dysfunction is a prominent early event in the progression of Alzheimer’s disease (AD). Whether protecting mitochondrial function can reduce amyloid-β oligomer (AβO)-induced neurotoxicity in PS1V97L transgenic mice remains unknown. In this study, we examined the possible protective effects of honokiol (HKL) on mitochondrial dysfunction induced by AβOs in neurons, and cognitive function in AD PS1V97L transgenic mice. We determined that HKL increased mitochondrial sirtuin 3 (SIRT3) expression levels and activity, which in turn markedly improved ATP production and weakened mitochondrial reactive oxygen species production. We demonstrated that the enhanced energy metabolism and attenuated …oxidative stress of HKL restores AβO-mediated mitochondrial dysfunction in vitro and in vivo . Consequently, memory deficits in the PS1V97L transgenic mice were rescued by HKL in the early stages. These results suggest that HKL has therapeutic potential for delaying the onset of AD symptoms by alleviating mitochondrial impairment and increasing hyperactivation of SIRT3 in the pathogenesis of preclinical AD. Show more

Keywords: Alzheimer’s disease, amyloid-β protein, cognitive dysfunction, mitochondria, sirtuin 3 (SIRT3)

DOI: 10.3233/JAD-180126

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 291-302, 2018

Authors: Baranowski, Bradley J. | Hayward, Grant C. | Fajardo, Val A. | MacPherson, Rebecca E.K.

Article Type: Research Article

Abstract: Background/Objective: To compare Alzheimer’s disease (AD) mortality rates and coinciding risk factors in rural and urban Texas populations. Methods: 155 Texas counties were divided into 73 rural and 82 urban areas using the U.S. Census Bureau definition of rurality. Changes in age-adjusted AD mortality across these counties were calculated using a 7-year aggregation model from 2000–2006 and 2009–2015. Data pertaining to gender, race, education, obesity, diabetes, physical inactivity, and lithium concentrations in tap water were also collected from readily available databases. Results: Change in age-adjusted AD mortality was higher in rural counties (9.5±1.4) versus urban (5.9±1.1) …over the time period examined. Similarly, obesity (30.2±0.2% ), diabetes (11.0±0.1% ), and physical inactivity (29.4±0.2% ) levels were significantly higher in rural populations compared to urban (29.1±0.2%, 9.7±0.1%, and 26.7±0.3, respectively). In contrast, the percent of population with some college education (40.1±0.7% ) was lower compared to urban (29.4±0.2% and 44.4±0.9%, respectively). Lithium concentrations in tap water was significantly lower in rural counties compared to urban (63.3±8.2 and 33.4±4.7μg/L, respectively). No significant differences were observed among females and however, we did find significant differences in the percent of African American and Hispanics. Correlational analysis uncovered a negative association between education status and AD mortality over time (r  = –0.17). Further analysis controlling for physical inactivity, education, and trace lithium concentrations results in a loss of statistical significance. Conclusions: AD mortality rates are higher in rural counties when compared to urban counties, and this may be linked to greater physical inactivity, obesity, and diabetes, as well as lower trace lithium levels in tap water. Show more

Keywords: Dementia, insulin, metabolic disorders, physical activity

DOI: 10.3233/JAD-171150

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 303-308, 2018

Authors: Du, Yehong | Fu, Min | Wang, Yu Tian | Dong, Zhifang

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by the deposition of amyloid-β peptides (Aβ). Aβ accumulation leads to the formation of neurofibrillary tangles, inflammation, axonal injury, synapse loss, and neuronal apoptosis. Thus, reducing Aβ levels should exert a neuroprotective effect against AD. Ginsenoside Rf, an extract from Panax notoginseng, has potent anti-fatigue, anti-nociception, anti-oxidation, and anti-inflammation properties. However, it is unclear whether ginsenoside Rf is effective in the treatment of AD. Here, we reported that ginsenoside Rf could significantly attenuate Aβ-induced apoptosis in N2A cells, as reflected by a dramatic increase in mitochondrial membrane potential and decrease in Ca2 …+ concentration, reactive oxygen species, and active caspase-3 expression. Meanwhile, ginsenoside Rf could alleviate the Aβ-induced inflammation reaction, such as the decrease of interferon-gamma (IFN-γ ) and active caspase-1 expression and the increase of interleukin-13. Furthermore, we also found that Rf is able to accelerate Aβ clearance and subsequently reduces Aβ level in N2A cells stably transfected with human Swedish mutant APP695 (N2A-APP). More importantly, daily Rf treatment (20 mg/kg, i.p.) throughout the experiment dramatically improved spatial learning and memory in Aβ42 -induced mouse model of AD. Taken together, these results indicate that ginsenoside Rf may decrease Aβ-induced neurotoxicity and memory decline via anti-inflammatory response during AD development, suggesting that Rf may be a potential therapeutic agent for treating AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, anti-inflammation, ginsenoside Rf, learning, memory

DOI: 10.3233/JAD-180251

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 309-322, 2018

Authors: Shea, Yat-Fung | Barker, Warren | Greig-Gusto, Maria T. | Loewenstein, David A. | Duara, Ranjan | DeKosky, Steven T.

Article Type: Research Article

Abstract: Background: Patients with cognitive impairment or dementias of uncertain etiology are frequently referred to a memory disorders specialty clinic. The impact of and role for amyloid PET imaging (Aβ -PET) may be most appropriate in this clinical setting. Objective: The primary objective of this study was to perform a systematic review and meta-analysis of the impact of Aβ -PET on etiological diagnosis and clinical management in the memory clinic setting. Methods: A search of the literature on the impact of Aβ -PET in the memory clinic setting between 1 January 2004 and 12 …February 2018 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the impact of Aβ -PET in the changes of diagnoses and changes in management plan. Results: After rigorous review, results from 13 studies were extracted, involving 1,489 patients. Meta-analysis revealed a pooled effect of change in diagnoses of 35.2% (95% CI 24.6–47.5). Sub-analyses showed that the pooled effect in change in diagnoses if Aβ -PET was used under the appropriate use criteria (AUC) or non-AUC criteria were 47.8% (95% CI 25.9–70.5) and 29.6% (95% CI: 21.5–39.3), respectively. The pooled effect of a change of diagnosis from Alzheimer’s disease (AD) to non-AD and from non-AD to AD were 22.7% (95% CI: 17.1–29.5) and 25.6% (95% CI: 17.6–35.8), respectively. The pooled effect leading to a change of management was 59.6% (95% CI 39.4–77.0). Conclusions: Aβ -PET has a highly significant impact on both changes in diagnosis and management among patients being seen at a specialty memory clinic. Show more

Keywords: Alzheimer’s disease, amyloid imaging, diagnosis, management, memory clinic, positron emission tomography

DOI: 10.3233/JAD-180239

Citation: Journal of Alzheimer's Disease, vol. 64, no. 1, pp. 323-335, 2018