Journal of Alzheimer's Disease - Volume 60, issue 2

Authors: Tremolizzo, Lucio | Bianchi, Elisa | Susani, Emanuela | Pupillo, Elisabetta | Messina, Paolo | Aliprandi, Angelo | Salmaggi, Andrea | Cosseddu, Maura | Pilotto, Andrea | Borroni, Barbara | Padovani, Alessandro | Bonomini, Cristina | Zanetti, Orazio | Appollonio, Ildebrando | Beghi, Ettore | Ferrarese, Carlo

Article Type: Short Communication

Abstract: Alcohol, coffee, and tobacco consumption was assessed on 151 FTD outpatients and 151 matched controls in a multicenter retrospective case-control design. No association was found for smoking and coffee intake. The risk of FTD was decreased by alcohol consumption (adj. OR 0.30, 95% CI 0.14–0.63); risk reduction was significant in current alcohol consumers (adj. OR 0.22, 95% CI 0.10–0.51). The risk of FTD inversely correlated with the duration of exposure (adj. OR 0.88, 95% CI 0.81–0.95, for every 5 years of exposure increase). Retrospective information and the unknown amount of consumed alcohol are limits of the present work.

Keywords: Alcohol, coffee, frontotemporal dementia, risk factor, smoking, voluptuary habits

DOI: 10.3233/JAD-170260

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 335-340, 2017

Authors: Chung, Jun Ku | Plitman, Eric | Nakajima, Shinichiro | Caravaggio, Fernando | Shinagawa, Shunichiro | Iwata, Yusuke | Gerretsen, Philip | Kim, Julia | Takeuchi, Hiroyoshi | Patel, Raihaan | Chakravarty, M. Mallar | Strafella, Antonio | Graff-Guerrero, Ariel | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Short Communication

Abstract: The clinical and structural trajectories of suspected non-Alzheimer’ pathology (SNAP) remain elusive due to its heterogeneous etiology. Baseline and longitudinal clinical (global cognition, daily functioning, symptoms of dementia, and learning memory) and hippocampal volume trajectories over two years were compared between patients with amnestic mild cognitive impairment (aMCI) with SNAP with reduced hippocampal volumes (SNAP+HIPPO) and aMCI patients with SNAP without reduced hippocampal volumes. SNAP+HIPPO showed overall worse baseline cognitive functions. Longitudinally, SNAP+HIPPO showed faster deterioration of clinical symptoms of dementia. Having both hippocampal atrophy and cortical hypometabolism without amyloid pathology may exacerbate symptoms of dementia in aMCI.

Keywords: Functional decline, hippocampus, mild cognitive impairment, suspected non-Alzheimer’s pathology

DOI: 10.3233/JAD-170098

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 341-347, 2017

Authors: Cross, Amanda J. | George, Johnson | Woodward, Michael C. | Ames, David | Brodaty, Henry | Wolfe, Rory | Connors, Michael H. | Elliott, Rohan A.

Article Type: Research Article

Abstract: Background: There is limited evidence regarding the association between potentially inappropriate medications (PIM) and mortality in older people with cognitive impairment. Objective: To examine whether use of medications considered to be potentially inappropriate in older people with cognitive impairment (PIMcog) and anticholinergic cognitive burden (ACB) were associated with mortality in people who attended memory clinics. Methods: Cross-sectional and longitudinal analyses of data from the Prospective Research In MEmory clinics (PRIME) study. Participants were community-dwelling people who attended nine memory clinics and had a diagnosis of mild cognitive impairment or dementia. PIMcog was defined as any medication …considered potentially inappropriate for a person with cognitive impairment according to Beers or STOPP criteria. Anticholinergic burden was calculated using the ACB scale. Time-dependent Cox-proportional hazards regression was used to analyze associations between PIMcog use/ACB score and all-cause mortality over a three-year follow-up period. The regression model included the baseline variables: age, gender, education, cognitive diagnoses, total number of medications, disease-burden, cognition, physical function, and neuropsychiatric symptoms. Results: Of 964 participants, 360 (37.3%) used one or more PIMcog at some time during the study; most commonly anticholinergics and sedatives. 624 (64.7%) participants used a medication with potential or definite anticholinergic properties (ACB>0) at some point during the study. Both PIMcog use (adjusted hazard ratio: 1.42 95% CI: 1.12–1.80) and ACB score (adjusted hazard ratio: 1.18 95% CI: 1.06–1.32) were associated with mortality. Conclusion: Use of PIMcogs and medications with anticholinergic properties was common among memory clinic patients and both were associated with mortality. Show more

Keywords: Alzheimer’s disease, cholinergic antagonists, cognitive dysfunction, dementia, inappropriate prescribing, mortality, potentially inappropriate medication list, contstartabstract

DOI: 10.3233/JAD-170265

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 349-358, 2017

Authors: Rokad, Farheen | Moseley, Ryan | Hardy, Rowan S. | Chukkapalli, Sasanka | Crean, StJohn | Kesavalu, Lakshmyya | Singhrao, Sim K.

Article Type: Research Article

Abstract: The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain. This study examined oxidative stress, in the form of increased protein carbonylation and oxidative protein damage, in the tumor necrosis factor-α (TNF-α) transgenic mouse that models inflammatory TNF-α excess during bacterial infection; and in the apolipoprotein knockout (ApoE– / – ) mouse brains, following Porphyromonas gingivalis gingival monoinfection. Following 2,4-dinitrophenylhydrazine derivatization, carbonyl groups were detected in frontal lobe brain tissue lysates by immunoblotting and immunohistochemical analysis of fixed tissue sections from the frontotemporal lobe and the …hippocampus. Immunoblot analysis confirmed the presence of variable carbonyl content and oxidative protein damage in all lysates, with TNF-α transgenic blots exhibiting increased protein carbonyl content, with consistently prominent bands at 25 kDa (p  = 0.0001), 43 kDa, and 68 kDa, over wild-type mice. Compared to sham-infected ApoE–/– mouse blots, P. gingivalis -infected brain tissue blots demonstrated the greatest detectable protein carbonyl content overall, with numerous prominent bands at 25 kDa (p  = 0.001) and 43 kDa (p  = 0.0001) and an exclusive band to this group between 30–43 kDa* (p  = 0.0001). In addition, marked immunostaining was detected exclusively in the microvasculature in P. gingivalis -infected hippocampal tissue sections, compared to sham-infected, wild-type, and TNF-α transgenic mice. This study revealed that the hippocampal microvascular structure of P. gingivalis -infected ApoE– / – mice possesses elevated oxidative stress levels, resulting in the associated tight junction proteins being susceptible to increased oxidative/proteolytic degradation, leading to a loss of functional integrity. Show more

Keywords: Hippocampus, infection, microvasculature, oxidative stress/damage, Porphyromonas gingivalis, tight junction proteins

DOI: 10.3233/JAD-170304

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 359-369, 2017

Authors: Hao, Lixiao | Wang, Xiaoni | Zhang, Ling | Xing, Yue | Guo, Qihao | Hu, Xiaochen | Mu, Bin | Chen, Yili | Chen, Guanqun | Cao, Jing | Zhi, Xiaodong | Liu, Jiaojiao | Li, Xuanyu | Yang, Liu | Li, Jiachen | Du, Wenying | Sun, Yu | Wang, Ting | Liu, Zhen | Liu, Zheng | Zhao, Xuexue | Li, Hongyan | Yu, Yang | Wang, Xue | Jia, Jianguo | Han, Ying

Article Type: Research Article

Abstract: Background: Substantial studies have reported the prevalence and the affecting factors of subjective cognitive decline (SCD). The complaints screening scale has also been used for probing. However, little is known in China. Objective: To investigate the prevalence and risk factors of SCD, and explore an SCD complaints screening scale in China. Methods: Stratified cluster random sampling was conducted. 2,689 residents aged 60–80 years completed questionnaire 1. 814 residents were included for clinical and neuropsychological evaluations. Two standards were used to make the diagnosis of mild cognitive impairment (MCI) and SCD, and a preliminary screening rate …comparison was carried out. Finally, we assessed the risk factors of SCD and the correlation between the SCD-questionnaire 9 (SCD-Q9) and the Auditory Verbal Learning Test-Long Delay Free Recall (AVLT-LR). Results: 1) Standard 1 (ADNI2): the prevalence of SCD was 18.8% (95% CI = 14.7–22.9%) and zero conformed to six criteria (SCD plus). 2) Standard 2 (Jak/Bondi): the prevalence of SCD was 14.4% (95% CI = 10.7–18.1%). 3) Standard 1 had a relatively higher “false” positive rate, whereas Standard 2 had higher “false” negative rate. 4) Age, low education, fewer close friends, and daily drinking were independent risk factors for SCD progressing to MCI. 5) Total points of SCD-Q9 were negatively correlated to the value of AVLT-LR. Conclusions: The prevalence of SCD is high in the ShunYi District in Beijing, China. Age, low education, less social support, and daily drinking are independent risk factors. The brief SCD-Q9 can be used as a reference. Show more

Keywords: Alzheimer’s disease, prevalence, risk factors, SCD-Q9, subjective cognitive decline

DOI: 10.3233/JAD-170347

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 371-388, 2017

Authors: Tao, Jing | Liu, Jiao | Liu, Weilin | Huang, Jia | Xue, Xiehua | Chen, Xiangli | Wu, Jinsong | Zheng, Guohua | Chen, Bai | Li, Ming | Sun, Sharon | Jorgenson, Kristen | Lang, Courtney | Hu, Kun | Chen, Shanjia | Chen, Lidian | Kong, Jian

Article Type: Research Article

Abstract: The aim of this study is to investigate and compare how 12-weeks of Tai Chi Chuan and Baduanjin exercise can modulate brain structure and memory function in older adults. Magnetic resonance imaging and memory function measurements (Wechsler Memory Scale-Chinese revised, WMS-CR) were applied at both the beginning and end of the study. Results showed that both Tai Chi Chuan and Baduanjin could significantly increase grey matter volume (GMV) in the insula, medial temporal lobe, and putamen after 12-weeks of exercise. No significant differences were observed in GMV between the Tai Chi Chuan and Baduanjin groups. We also found that compared …to healthy controls, Tai Chi Chuan and Baduanjin significantly improved visual reproduction subscores on the WMS-CR. Baduanjin also improved mental control, recognition, touch, and comprehension memory subscores of the WMS-CR compared to the control group. Memory quotient and visual reproduction subscores were both associated with GMV increases in the putamen and hippocampus. Our results demonstrate the potential of Tai Chi Chuan and Baduanjin exercise for the prevention of memory deficits in older adults. Show more

Keywords: Aging, Baduanjin, memory, mind-body exercise, Tai Chi Chuan, voxel-based morphometry

DOI: 10.3233/JAD-170477

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 389-400, 2017

Authors: Kishi, Taro | Matsunaga, Shinji | Oya, Kazuto | Nomura, Ikuo | Ikuta, Toshikazu | Iwata, Nakao

Article Type: Research Article

Abstract: Background: The clinical benefit of memantine for Alzheimer’s disease (AD) remains inconclusive. Objective: We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD. Methods: We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses. Results: Thirty studies (n  = 7,567; memantine versus placebo: N = 11, n  = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n  = 4,175) were identified. Memantine showed a significant improvement …in CF [standardized mean difference (SMD) = –0.24, 95% confidence intervals (95% CIs) = –0.34, –0.15, p  < 0.00001, I2  = 35% ] and BD (SMD = –0.16, 95% CIs = –0.29, –0.04, p  = 0.01, I2  = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate–severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = –0.20, 95% CIs = –0.34, –0.07, p  = 0.003, I2  = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = –0.20, 95% CIs = –0.36, –0.03, p  = 0.02, I2  = 77%) and a trend of CF improvement (SMD = –0.11, 95% CIs = –0.22, 0.01, p  = 0.06, I2  = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = –0.11, 95% CIs = –0.21, –0.01, p  = 0.04, I2  = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = –0.18, 95% CIs = –0.31, –0.05, p  = 0.006, I2  = 49%). No differences were detected in all-cause discontinuation between the groups. Conclusions: The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs. Show more

Keywords: Alzheimer’s disease, behavioral disturbances, cognitive function, memantine, meta-analysis, systematic review

DOI: 10.3233/JAD-170424

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 401-425, 2017

Authors: Li, Clara | Neugroschl, Judith | Luo, Xiaodong | Zhu, Carolyn | Aisen, Paul | Ferris, Steven | Sano, Mary

Article Type: Research Article

Abstract: Background: Subjective cognitive complaint is a sensitive marker of decline. Objective: This study aimed to (1) examine reliability of subjective cognitive complaint using the Cognitive Function Instrument (CFI), and (2) assess the utility of the CFI to detect cognitive decline in non-demented elders. Methods: Data from a four-year longitudinal study at multiple Alzheimer’s Disease Cooperative Study (ADCS) sites were extracted (n  = 644). Of these, 497 had Clinical Dementia Rating (CDR) global scores of 0 and 147 had a CDR of 0.5. Mean age and education were 79.5±3.6 and 15.0±3.1 years, respectively. All participants and their study …partners completed the subject and study partner CFI yearly. Modified Mini-Mental State Exam (mMMSE) and Free and Cued Selective Reminding Test (FCSRT) were administered. Scores below the predetermined cut-off scores on either measure at annual visit were triggers for a full diagnostic evaluation. Cognitive decline was defined by the absence/presence of the trigger. Results: Three-month test retest reliability showed that inter-class coefficients for subject and study partner CFI were 0.76 and 0.78, respectively. Generalized estimating equation method revealed that both subject and study partner CFI change scores and scores from previous year were sensitive to cognitive decline in the CDR 0 group (p  < 0.05). In the CDR 0.5 group, only the study partner CFI change score predicted cognitive decline (p  < 0.05). Conclusion: Cognitive decline was predicted differentially by CDR level with subject CFI scores providing the best prediction for those with CDR 0 while study partner CFI predicted best for those at CDR 0.5. Show more

Keywords: Cognitive decline, healthy older adults, non-demented elders, subjective cognitive complaints

DOI: 10.3233/JAD-161294

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 427-437, 2017

Authors: Rafii, Michael S. | Lukic, Ana S. | Andrews, Randolph D. | Brewer, James | Rissman, Robert A. | Strother, Stephen C. | Wernick, Miles N. | Pennington, Craig | Mobley, William C. | Ness, Seth | Matthews, Dawn C. | for the Down Syndrome Biomarker Initiative and the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer’s disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations. Objectives: 1) Understand the relationship between tau pathology and age, amyloid deposition, neurodegeneration (MRI and FDG PET), and cognitive and functional performance; 2) detect and differentiate AD-specific changes from DS-specific brain changes in longitudinal MRI. Methods: Twelve non-demented adults, ages 30 to 60, with DS were enrolled in the Down Syndrome Biomarker Initiative (DSBI), a 3-year, observational, cohort study …to demonstrate the feasibility of conducting AD intervention/prevention trials in adults with DS. We collected imaging data with 18 F-AV-1451 tau PET, AV-45 amyloid PET, FDG PET, and volumetric MRI, as well as cognitive and functional measures and additional laboratory measures. Results: All amyloid negative subjects imaged were tau-negative. Among the amyloid positive subjects, three had tau in regions associated with Braak stage VI, two at stage V, and one at stage II. Amyloid and tau burden correlated with age. The MRI analysis produced two distinct volumetric patterns. The first differentiated DS from normal (NL) and AD, did not correlate with age or amyloid, and was longitudinally stable. The second pattern reflected AD-like atrophy and differentiated NL from AD. Tau PET and MRI atrophy correlated with several cognitive and functional measures. Conclusions: Tau accumulation is associated with amyloid positivity and age, as well as with progressive neurodegeneration measurable using FDG and MRI. Tau correlates with cognitive decline, as do AD-specific hypometabolism and atrophy. Show more

Keywords: Alzheimer’s disease, biomarkers, dementia, Down syndrome, Tau PET, volumetric MRI

DOI: 10.3233/JAD-170390

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 439-450, 2017

Authors: Morales, Inelia | Cerda-Troncoso, Cristóbal | Andrade, Víctor | Maccioni, Ricardo B.

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive cognitive impairment of patients, affecting around 12% of people older than 65 years old. WHO estimated that over 48.6 million all over the world suffer this disease. On the basis of cumulative results on our research, we have postulated the neuroimmunomodulation hypothesis that appears to provide a reasonable explanation of both the preclinical and clinical observations. In this context, the long-term activation of the innate immune system triggers an anomalous cascade of molecular signals, finally leading to tau oligomerization in the pathway to neuronal degeneration. In the present scenario …of the failure of many anti-AD drugs, nutraceutical compounds provide an avenue for AD prevention and possibly as coadjuvants in the treatment of this disease. Recent discoveries point to the relevance of curcumin, a natural anti-inflammatory agent, in controlling oxidative stress and improving cholinergic function in the brain, even though the mechanisms underlying these actions are unknown. We investigated the effects of curcumin in cultures of neuronal cells. For this study, we exposed cells to prooxidant conditions, both in the presence and absence of curcumin. Our data reveal that curcumin exert a strong neuroprotective effect in N2a cells, thus preventing toxicity by oxidative agents H2 O2 and Fe+3 . This is supported by results that indicate that curcumin control the neurodegenerative effects of both oxidative agents, relieving cells from the loss of neuritogenic processes induced by prooxidants. In addition, curcumin was able to slow down the tau aggregation curve and disassemble tau pathological oligomeric structures. Data suggest that curcumin could be a potential compound for prevention of cognitive disorders associated with AD. Show more

Keywords: Alzheimer’s disease, curcumin and derivatives, functional effects in neurons, prevention, treatment

DOI: 10.3233/JAD-170354

Citation: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 451-460, 2017