Journal of Alzheimer's Disease - Volume 60, issue 4

Authors: Dardenne, Sophie | Delrieu, Julien | Sourdet, Sandrine | Cantet, Christelle | Andrieu, Sandrine | Mathiex-Fortunet, Hélène | Fougère, Bertrand | Vellas, Bruno

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) may be a very early symptom of Alzheimer’s disease (AD) and may be associated with a cognitive decline in a cognitively normal population. The McNair and Kahn Scale was used to assess memory complaints in the GuidAge study. Objective: Our objectives were to examine if the McNair and Kahn Scale can predict cognitive decline and to screen which (if any) of the question(s) of this scale would better predict this cognitive decline. Methods: The GuidAge study was a phase III, multicenter, randomized, double blind, placebo-controlled study. Individuals aged 70 years and …older, without cognitive impairment (Clinical Dementia Rate (CDR = 0)) at baseline who had spontaneously reported SCD were included in this study. The 20-item version of the McNair and Kahn Scale was used to assess SCD and a standardized neuropsychological assessment was used to assess the cognitive status. Results: 1,307 patients with SCD and with CDR = 0 at baseline were included. During the 5 years of follow-up, 519 patients showed cognitive decline. Incidence of aggravation score of CDR was 13.40% person years (95% CI [12.24–14.56]). Results showed a significant relationship between the McNair and Kahn Scale score and decline in cognitive performance (HR 1.012; 95% CI [1.002–1.021]; p  = 0.0156). Among the 20 items, 5 were statistically significant to predict cognitive decline after adjustment. Conclusion: SCD is a promising indicator of memory impairment. Our study found that using the McNair and Kahn scale can predict cognitive decline. A 5-item version of this scale could be used to screen patients in clinical practice and in clinical research. Show more

Keywords: Alzheimer’s disease, cognitive decline, memory complaint, preclinical stage, subjective cognitive complaint

DOI: 10.3233/JAD-170229

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1567-1578, 2017

Authors: Jang, Hyemin | Ye, Byoung Seok | Woo, Sookyoung | Kim, Sun Woo | Chin, Juhee | Choi, Seong Hye | Jeong, Jee Hyang | Yoon, Soo Jin | Yoon, Bora | Park, Kyung Won | Hong, Yun Jeong | Kim, Hee Jin | Lockhart, Samuel N. | Na, Duk L. | Seo, Sang Won

Article Type: Research Article

Abstract: Background: Patients with amnestic mild cognitive impairment (aMCI) have an increased risk of dementia. However, conversion rate varies. Therefore, predicting the dementia conversion in these patients is important. Objective: We aimed to develop a nomogram to predict dementia conversion in aMCI subjects using neuropsychological profiles. Methods: A total of 338 aMCI patients from two hospital-based cohorts were used in analysis. All patients were classified into 1) verbal, visual, or both, 2) early or late, and 3) single or multiple-domain aMCI according to the modality, severity of memory dysfunction, and multiplicity of involved cognitive domains, respectively. Patients …were followed up, and conversion to dementia within 3 years was defined as the primary outcome. Our patients were divided into a training data set and a validation data set. The associations of potential covariates with outcome were tested, and nomogram was constructed by logistic regression model. We also developed another model with APOE data, which included 242 patients. Results: In logistic regression models, both modalities compared with visual only (OR 4.44, 95% CI 1.83–10.75, p  = 0.001), late compared to early (OR 2.59, 95% CI 1.17–5.72, p  = 0.019), and multiple compared to single domain (OR 3.51, 95% CI 1.62–7.60, p  = 0.002) aMCI were significantly associated with dementia conversion within 3 years. A nomogram incorporating these clinical variables was constructed on the training data set and validated on the validation data set. Both nomograms with and without APOE data showed good prediction performance (c-statistics ≥ 0.75). Conclusions: This study showed that several neuropsychological profiles of aMCI are significantly associated with imminent dementia conversion, and a nomogram incorporating these clinical subtypes is simple and useful to help to predict disease progression. Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, nomogram, prediction model

DOI: 10.3233/JAD-170507

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1579-1587, 2017

Authors: Tuwaig, Miranda | Savard, Mélissa | Jutras, Benoît | Poirier, Judes | Collins, D. Louis | Rosa-Neto, Pedro | Fontaine, David | Breitner, John C.S. | for the PREVENT-AD Research Group

Article Type: Research Article

Abstract: Prevention of dementia due to Alzheimer’s disease (d/AD) requires interventions that slow the disease process prior to symptom onset. To develop such interventions, one needs metrics that assess pre-symptomatic disease progression. Familiar measures of progression include cerebrospinal fluid (CSF) biochemical and imaging analyses, as well as cognitive testing. Changes in the latter can sometimes be difficult to distinguish from effects of “normal” aging. A different approach involves testing of “central auditory processing” (CAP), which enables comprehension of auditory stimuli amidst a distracting background (e.g., conversation in a noisy bar or restaurant). Such comprehension is often impaired in d/AD. Similarly, effortful …or diminished auditory comprehension is sometimes reported by cognitively healthy elders, raising the possibility that CAP deficit may be a marker of pre-symptomatic AD. In 187 cognitively and physically healthy members of the aging, AD family history-positive PREVENT-AD cohort, we therefore evaluated whether CAP deficits were associated with known markers of AD neurodegeneration. Such markers included CSF tau concentrations and magnetic resonance imaging volumetric and cortical thickness measures in key AD-related regions. Adjusting for age, sex, education, pure-tone hearing, and APOE ɛ 4 status, we observed a persistent relationship between CAP scores and CSF tau levels, entorhinal and hippocampal cortex volumes, cortical thickness, and deficits in cognition (Repeatable Battery for Assessment of Neuropsychological Status total score, and several of its index scales). These cross-sectional observations suggest that CAP may serve as a novel metric for pre-symptomatic AD pathogenesis. They are therefore being followed up longitudinally with larger samples. Show more

Keywords: Biomarkers, central auditory processing disorder, cognitive function, pre-clinical Alzheimer’s disease, prevention, sensorineural assessment

DOI: 10.3233/JAD-170545

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1589-1600, 2017

Authors: Torrens-Burton, Anna | Basoudan, Nasreen | Bayer, Antony J. | Tales, Andrea

Article Type: Research Article

Abstract: This study examines the relationships between two measures of information processing speed associated with executive function (Trail Making Test and a computer-based visual search test), the perceived difficulty of the tasks, and perceived memory function (measured by the Memory Functioning Questionnaire) in older adults (aged 50+ y) with normal general health, cognition (Montreal Cognitive Assessment score of 26+), and mood. The participants were recruited from the community rather than through clinical services, and none had ever sought or received help from a health professional for a memory complaint or mental health problem. For both the trail making and the visual search …tests, mean information processing speed was not correlated significantly with perceived memory function. Some individuals did, however, reveal substantially slower information processing speeds (outliers) that may have clinical significance and indicate those who may benefit most from further assessment and follow up. For the trail making, but not the visual search task, higher levels of subjective memory dysfunction were associated with a greater perception of task difficulty. The relationship between actual information processing speed and perceived task difficulty also varied with respect to the task used. These findings highlight the importance of taking into account the type of task and metacognition factors when examining the integrity of information processing speed in older adults, particularly as this measure is now specifically cited as a key cognitive subdomain within the diagnostic framework for neurocognitive disorders. Show more

Keywords: Aging, information processing speed, metacognition, reaction time, subjective cognitive impairment

DOI: 10.3233/JAD-170599

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1601-1609, 2017

Authors: Piers, Ryan J. | Devlin, Kathryn N. | Ning, Boting | Liu, Yulin | Wasserman, Ben | Massaro, Joseph M. | Lamar, Melissa | Price, Catherine C. | Swenson, Rod | Davis, Randall | Penney, Dana L. | Au, Rhoda | Libon, David J.

Article Type: Research Article

Abstract: Background: Digital Clock Drawing Test (dCDT) technology enables the examination of detailed neurocognitive behavior as behavior unfolds in real time; a capability that cannot be obtained using a traditional pen and paper testing format. Objective: Parameters obtained from the dCDT were used to investigate neurocognitive constructs related to higher-order neurocognitive decision making and information processing speed. The current research sought to determine the effect of age as related to combined motor and non-motor components of drawing, and higher-order decision making latencies. Methods: A large group of stroke- and dementia- free Framingham Heart Study participants were administered …the dCDT to command and copy with hands set for “10 after 11 ”. Six age groups (age range 28–98) were constructed. Results: Differences between age groups were found for total time to completion, total pen stroke count, and higher-order decision making latencies in both command and copy test conditions. Conclusion: Longer age-related decision making latencies may reflect a greater need for working memory and increased self-monitoring in older subjects. These latency measures have potential to serve as neurocognitive biomarkers of Alzheimer’s disease and other insidious neurodegenerative disorders. Show more

Keywords: Boston Process Approach, cognition, digital clock drawing test, graphomotor decision making, normal aging

DOI: 10.3233/JAD-170444

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1611-1620, 2017

Authors: Kirsebom, Bjørn-Eivind | Espenes, Ragna | Waterloo, Knut | Hessen, Erik | Johnsen, Stein Harald | Bråthen, Geir | Aarsland, Dag | Fladby, Tormod

Article Type: Research Article

Abstract: Background: Cognitive assessment is essential in tracking disease progression in AD. Presently, cohorts including preclinical at-risk participants are recruited by different means, which may bias cognitive and clinical features. We compared recruitment strategies to levels of cognitive functioning. Objective: We investigate recruitment source biases in self-referred and memory clinic-referred patient cohorts to reveal potential differences in cognitive performance and demographics among at-risk participants. Methods: We included 431 participants 40–80 years old. Participants were classified as controls (n  = 132) or symptom group (n  = 299). The symptom group comprised of subjective cognitive decline (SCD, n  = 163) and mild …cognitive impairment (MCI, n  = 136). We compared cognitive performance and demographics in memory clinic-referrals (n  = 86) to self-referred participants responding to advertisements and news bulletins (n  = 179). Participants recruited by other means were excluded from analysis (n  = 34). Results: At symptom group level, we found significant reductions in cognitive performance in memory clinic-referrals compared to self-referrals. However, here reductions were only found within the MCI group. We found no differences in cognitive performance due to recruitment within the SCD group. The MCI group was significantly impaired compared to controls on all measures. Significant reductions in learning, and executive functions were also found for the SCD group. Conclusion: Regardless of recruitment method, both the SCD and MCI groups showed reductions in cognitive performance compared to controls. We found differences in cognitive impairment for memory clinic-referrals compared to self-referrals only within the MCI group, SCD-cases being equally affected irrespective of referral type. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, mild cognitive impairment, patient recruitment, research subject recruitment, sampling studies, subjective cognitive decline

DOI: 10.3233/JAD-170385

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1621-1631, 2017

Authors: Cowan, Ronald L. | Beach, Paul A. | Atalla, Sebastian W. | Dietrich, Mary S. | Bruehl, Stephen P. | Deng, Jie | Wang, Jinjiao | Newhouse, Paul A. | Gore, John C. | Monroe, Todd B.

Article Type: Research Article

Abstract: Background: People with Alzheimer’s disease (AD) report pain less frequently and receive less pain medication than people without AD. Recent studies have begun to elucidate how pain may be altered in those with AD. However, potential sex differences in pain responsiveness have never been explored in these patients. It is unclear whether sex differences found in prior studies of healthy young and older individuals extend to people with AD. Objective: The purpose of this study was to examine sex differences in the psychophysical response to experimental thermal pain in people with AD. Methods: Cross-sectional analysis of …14 male and 14 female age-matched (≥65 years of age, median = 74) and AD severity-matched (Mini-Mental State Exam score <24, median = 16) communicative people who completed thermal psychophysics. Results: There was a statistically significant main effect of sex for both temperature and unpleasantness ratings that persisted after controlling for average and current pain (mixed-effects general liner model: temperature: p  = 0.004, unpleasantness: p  < 0.001). Females reported sensing mild pain and moderate pain percepts at markedly lower temperatures than did males (mild: Cohen ’s d  = 0.72, p  = 0.051, moderate: Cohen ’s d  = 0.80, p  = 0.036). By contrast, males rated mild and moderate thermal pain stimuli as more unpleasant than did females (mild: Cohen ’s d  = 0.80, p  = 0.072, moderate: Cohen ’s d  = 1.32, p  = 0.006). There were no statistically significant correlations of temperature with perceived unpleasantness for mild or moderate pain (rs  = 0.29 and rs  = 0.20 respectively, p  > 0.05). Conclusions: Results suggest experimental pain-related sex differences persist in older adults with AD in a different manner than those previously demonstrated in cognitively intact older adults. These findings could potentially aid in developing targeted pain management approaches in this vulnerable population. Further studies are warranted to replicate the findings from this pilot work. Show more

Keywords: Alzheimer’s disease, dementia, pain, pain threshold, perception, sex differences

DOI: 10.3233/JAD-170532

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1633-1640, 2017

Authors: Dayon, Loïc | Wojcik, Jérôme | Núñez Galindo, Antonio | Corthésy, John | Cominetti, Ornella | Oikonomidi, Aikaterini | Henry, Hugues | Migliavacca, Eugenia | Bowman, Gene L. | Popp, Julius

Article Type: Research Article

Abstract: Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer’s disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n  = 72) or without (n  = 48) cognitive impairment. CSF …Aβ1-42 , tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ1-42  > 0.0779, and presence of amyloidosis was defined as CSF Aβ1-42  < 724 pg/mL. Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%. Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD. Show more

Keywords: Alzheimer’s disease, amyloid-β, amyloidosis, biomarker, dementia, protein, tau

DOI: 10.3233/JAD-170426

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1641-1652, 2017

Article Type: Other

DOI: 10.3233/JAD-179006

Citation: Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1653-1665, 2017