Journal of Alzheimer's Disease - Volume 62, issue 1

Authors: Phua, April Ka Sin | Hiu, Shaun Kuan Wei | Goh, Win King | Ikram, Mohammad Kamran | Venketasubramanian, Narayanaswamy | Tan, Boon Yeow | Chen, Christopher Li-Hsian | Xu, Xin

Article Type: Research Article

Abstract: Background: Researchers have questioned the utility of brief cognitive tests such as the Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) in serial administration and suggested that brief cognitive tests may not accurately track changes in Global Cognition. Objective: To examine the accuracy of longitudinal changes on brief cognitive tests in reflecting progression in Global Cognition measured using comprehensive neuropsychological assessments. Methods: Two hundred and seven participants were assessed with the MMSE, MoCA, and a validated comprehensive neuropsychological battery. Global z-scores on the battery were derived and used to assess overall and significant (≥0.5 …standard deviation) decline on Global Cognition. Different patterns of decline on MMSE/MoCA were classified. Accuracy was examined using receiver operating characteristic curve, and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were reported. Results: The overall ability of MMSE/MoCA change scores to discriminate participants who did and did not decline on Global Cognition was fair-to-moderate (AUC [95% CI] = 0.71 [0.64–0.78] & 0.73 [0.66–0.80] for overall decline; 0.78 [0.70–0.85] & 0.80 [0.73–0.86] for significant decline, respectively). Changes in MMSE/MoCA had low accuracy in identifying significant Global Cognitive Decline (PPV = 0.41 & 0.46, respectively) but high accuracy in ruling out significant decline and identifying cognitively stable participants (NPV = 0.89 & 0.88, respectively). Conclusion: There is limited utility in brief cognitive tests for tracking cognitive decline. Instead, they should be used for identifying participants who remain cognitively stable on follow up. These results accentuate the importance of acknowledging the limitations of brief cognitive tests when assessing cognitive change. Show more

Keywords: Cognitive decline, cognitive impairments, dementia, geriatric assessment, longitudinal studies, neuropsychological test, outpatient clinic

DOI: 10.3233/JAD-170831

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 409-416, 2018

Authors: Malpas, Charles B. | Saling, Michael M. | Velakoulis, Dennis | Desmond, Patricia | Hicks, Rodney J. | Zetterberg, Henrik | Blennow, Kaj | O’Brien, Terence J.

Article Type: Research Article

Abstract: The two cardinal pathologies of Alzheimer’s disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer’s type. Interrelationships were analyzed between cerebrospinal fluid biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18 F]-FDG-PET. Amyloid-related pathology was …preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks. Show more

Keywords: Alzheimer’s disease, amyloid-β, cerebral glucose uptake, cerebrospinal fluid, cortical thickness, P-tau

DOI: 10.3233/JAD-170250

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 417-427, 2018

Authors: Xu, Qing-qing | Shan, Chun-shuo | Wang, Yong | Shi, Yi-hua | Zhang, Qi-hao | Zheng, Guo-qing

Article Type: Research Article

Abstract: Background: Vascular dementia (VaD) is the second common form of dementia and Chinese herbal medicine (CHM) has been used for aging-related disorders for thousands of years. However, there is still a lack of scientific evidence using CHM for VaD. Objective: To conduct a systematic review to assess the current evidence available for the effectiveness and safety of CHM for VaD. Methods: Six databases were searched for high-quality randomized-controlled clinical trials that met the requirements of at least 4 of the 7 domains of the Cochrane risk of bias tool from their inception to February 2017. RevMan …5.3 was applied for data analysis. Results: Forty studies with 42 comparisons and 3,572 individuals were included. The studies investigated the CHM versus placebo (n  = 4), CHM versus western conventional treatment (WCT) (n  = 36), and CHM plus WCT versus WCT (n  = 2). Meta-analysis showed that CHM for VaD could improve Mini-Mental State Examination (MMSE), the Activities of Daily Living, Hasegawa’s dementia scale, and clinical effective rate but had statistically similar effect based on Blessed Behavior Scale (BBS) outcome when compared with WCTs. When compared with placebo, CHMs were more beneficial in improving MMSE but showed no significant difference in BBS scores. CHM as adjuvant therapy exerted an additive anti-VaD benefit on MMSE scores. The participants of CHM group had fewer adverse events than that of the placebo group or WCT group. Conclusion: The findings of the present study support, at least to an extent, that CHM can be recommended for routine use for treatment of VaD. Show more

Keywords: Chinese herbal, meta-analysis, systematic review, traditional Chinese medicine, vascular dementia

DOI: 10.3233/JAD-170856

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 429-456, 2018

Authors: Ritchie, Craig W. | Black, Christopher M. | Khandker, Rezaul K. | Wood, Robert | Jones, Eddie | Hu, Xiaohan | Ambegaonkar, Baishali M.

Article Type: Research Article

Abstract: To ensure that patients with dementia and their caregivers receive appropriate treatment and support, early diagnosis is essential but remains challenging. Real-world data from a multi-national, cross-sectional survey of physicians and their patients were analyzed to quantify the diagnostic pathway for dementia, including a focus on severity of patients’ cognitive impairment (CI) at the time of symptom onset, referral and subsequent diagnosis. Data were collected for 7,620 patients with CI. Most patients saw a healthcare professional within 1 year of first symptoms and received a diagnosis within 3–7 months of initial consultation. However, only 20% of patients received a diagnosis …before their disease progressed beyond the prodromal stage and 23.5% already had moderate CI at diagnosis. These findings show that the goal of identifying and diagnosing CI at the earliest stages of disease is, for many patients, not achieved. Efforts toward public awareness and proactive, earlier detection and intervention, must be maintained—indeed where possible invigorated. Show more

Keywords: Caregivers, cognitive impairment, consultation, diagnosis, earlier and intervention, early diagnosis, prodromal, real-world, referral

DOI: 10.3233/JAD-170864

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 457-466, 2018

Authors: Reale, Marcella | D’Angelo, Chiara | Costantini, Erica | Di Nicola, Marta | Yarla, Nagnedra Sastry | Kamal, Mohammad Amjad | Salvador, Nieves | Perry, George

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD), a neurodegenerative disease, is associated with dysfunction of the olfactory and the entorhinal cortex of the brain that control memory and cognitive functions and other daily activities. Pro-inflammatory cytokines, amyloid-β (Aβ), and the cholinergic system play vital roles in the pathophysiology of AD. However, the role of changes in cholinergic system components, Aβ accumulation, and cytokines in both the olfactory and entorhinal cortex is not known clearly. Objective: The present study is aimed to evaluate the changes of cholinergic system components, Aβ accumulation, and cytokines in both the olfactory bulb (OB) and entorhinal cortex …(EC) of young and aged APPSWE /PS1dE9 transgenic (Tg) mice. Methods: We have explored the changes of cholinergic system components, Aβ accumulation, and expression profiling of cytokines in the OB and EC of aged APPswe transgenic mice and age-matched wild type mice using quantitative Real-Time PCR assays and immunohistochemistry techniques. Results: In aged Tg mice, a significant increase of expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and chemokine MCP1 (p  < 0.001, p  < 0.001, and p  = 0.001, respectively) and a significant reduction of nAChRα4 (p  = 0.048) and AChE (p  = 0.023) was observed when compared with age-matched wild type mice. Higher levels of AChE and BuChE are expressed in OB and EC of the APPSWE /PS1dE9 of Tg mice. Aβ accumulation was observed in OB and EC of the APPSWE /PS1dE9 of Tg mice. Conclusion: The study demonstrates the expression profiling of pro-inflammatory cytokines and cholinergic markers as well as Aβ accumulation in OB and EC of the APPSWE /PS1dE9 Tg mice. Moreover, the study also demonstrated that the APPSWE /PS1dE9 Tg mice can be useful as a mouse model to understand the role of pro-inflammatory cytokines and cholinergic markers in pathophysiology of AD. Show more

Keywords: Aβ accumulation, Alzheimer’s disease, APPswe transgenic mice, cholinergic markers, pro-inflammatory cytokines

DOI: 10.3233/JAD-170999

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 467-476, 2018

Authors: Zhou, Futao | Chen, Shuangrong

Article Type: Research Article

Abstract: Leptin, as a link between fat mass and the brain, has been reported to be associated with gender. The gender differences in leptin levels between Alzheimer’s disease (AD) and healthy elderly controls are inconclusive so far. To quantitatively summarize the leptin data available from female and male patients with AD, we searched PubMed and EMBASE for articles published from inception to July 20, 2017. Data were extracted from 27 studies, consisting of 3,014 participants. The pooled results showed that the overall leptin levels were lower in AD (Hedges’ g  = –0.481; p  = 0.002) than in controls, and the leptin levels in …whole blood and serum were decreased with moderate and large effect sizes (g  = –0.677, –0.839; respectively; both of p -values <0.001) in AD compared with controls. In blood, there were significantly lower concentrations of leptin in female AD than in female controls (g  = –0.590; p  = 0.014), but not in male case-control group (g  = –0.666; p  = 0.067). Meta-regression analysis demonstrated that the decreased extent of leptin levels in AD paralleled the degree of the severity of dementia symptoms, as well as the alterations of body mass index (p -values ≤0.002). The findings provide strong evidence that 1) the blood concentrations of leptin are lower in female AD patients than in female controls; and 2) the greater the severity of dementia symptoms, the greater the decreases in the blood leptin levels. But more future investigations on the blood leptin levels in male AD patients is warranted. Show more

Keywords: Alzheimer’s disease, female, leptin, male, meta-analysis

DOI: 10.3233/JAD-170983

Citation: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 477-486, 2018