Journal of Alzheimer's Disease - Volume 61, issue 4

Authors: Hall, James R. | Wiechmann, April | Johnson, Leigh A. | Edwards, Melissa | O’Bryant, Sid E.

Article Type: Research Article

Abstract: Background: Subjective cognitive complaints in cognitively normal adults have been linked to later cognitive decline and dementia. Research on the characteristics of this group has been conducted on a variety of clinical and community-based populations. The current study focuses on the rapidly expanding population of Mexican-American elders. Objective: The objective of the study is the determination of characteristics of cognitively normal Mexican-Americans with cognitive complaints. Methods: Data on 319 cognitively normal participants in a large-scale community-based study of elderly Mexican-Americans (HABLE) were analyzed comparing those with cognitive complaints with those without on clinical characteristics, affective status, …neuropsychological functioning, and proteomic markers. Results: Those expressing concern about cognitive decline scored lower on the MMSE, were more likely to have significantly more affective symptoms, higher levels of diabetic markers, poorer performance on attention and executive functioning, and a different pattern of inflammatory markers. Conclusion: Although longitudinal research is needed to determine the impact of these differences on later cognition, possible targets for early intervention with Mexican-Americans were identified. Show more

Keywords: Affective symptoms, biomarkers, Mexican-Americans, subjective cognitive complaints

DOI: 10.3233/JAD-170836

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1485-1492, 2018

Authors: Konishi, Kyoko | Joober, Ridha | Poirier, Judes | MacDonald, Kathleen | Chakravarty, Mallar | Patel, Raihaan | Breitner, John | Bohbot, Véronique D.

Article Type: Research Article

Abstract: Early detection of Alzheimer’s disease (AD) has been challenging as current biomarkers are invasive and costly. Strong predictors of future AD diagnosis include lower volume of the hippocampus and entorhinal cortex, as well as the ɛ 4 allele of the Apolipoprotein E gene (APOE) gene. Therefore, studying functions that are critically mediated by the hippocampus and entorhinal cortex, such as spatial memory, in APOE ɛ 4 allele carriers, may be key to the identification of individuals at risk of AD, prior to the manifestation of cognitive impairments. Using a virtual navigation task developed in-house, specifically designed to assess spatial versus …non-spatial strategies, the current study is the first to differentiate functional and structural differences within APOE ɛ 4 allele carriers. APOE ɛ 4 allele carriers that predominantly use non-spatial strategies have decreased fMRI activity in the hippocampus and increased atrophy in the hippocampus, entorhinal cortex, and fimbria compared to APOE ɛ 4 allele carriers who use spatial strategies. In contrast, APOE ɛ 4 allele carriers who use spatial strategies have grey matter levels comparable to non-APOE ɛ 4 allele carriers. Furthermore, in a leave-one-out analysis, grey matter in the entorhinal cortex could predict navigational strategy with 92% accuracy. Show more

Keywords: APOE, entorhinal cortex, hippocampus, spatial memory

DOI: 10.3233/JAD-170540

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1493-1507, 2018

Authors: Beach, Thomas G. | Maarouf, Chera L. | Intorcia, Anthony | Sue, Lucia I. | Serrano, Geidy E. | Lu, Ming | Joshi, Abhinay | Pontecorvo, Michael J. | Roher, Alex E.

Article Type: Research Article

Abstract: Amyloid imaging demonstrates the in vivo presence of amyloid-β (Aβ) deposits in the aging human brain but it is still unknown which structural forms and modifications of Aβ are detected. In Alzheimer’s disease, most amyloid deposits are predominantly composed of Aβ ending at amino acid residues Val40 or Ala42. It has been reported that Aβ40 is largely restricted to neuritic plaques while Aβ42 may be deposited in amyloid plaques of all types, and is often the sole component of diffuse plaques. The distinction is important as it is mainly the neuritic plaques that correlate with cognitive impairment …while diffuse plaques may be the initial type of Aβ deposited. Whether PET amyloid ligands such as florbetapir-18 F (Amyvid) are partially or wholly selective for brain deposits of Aβ40 or Aβ42 is currently unknown. We compared antemortem florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with postmortem biochemical (ELISA) measurements employing specific antibodies against Aβ40 and Aβ42 . Spearman’s univariable correlations were significant for both Aβ40 and Aβ42 , but were much stronger for Aβ42 . Multiple linear regression showed significance only for Aβ42 . These results suggest that florbetapir binds only weakly, if at all, to Aβ40 . This may be in part due to the higher likelihood for Aβ42 to be present in a β-pleated sheet tertiary structure, or to differences between Aβ40 and Aβ42 in β-pleated sheet tertiary or quaternary structure. Show more

Keywords: Alzheimer’s disease, autopsy, diagnosis, diffuse plaque, neuritic plaque

DOI: 10.3233/JAD-170762

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1509-1516, 2018

Authors: Portacolone, Elena | Johnson, Julene K. | Covinsky, Kenneth E. | Halpern, Jodi | Rubinstein, Robert L.

Article Type: Research Article

Abstract: Background: One third of older adults with cognitive impairment live alone and are at high risk for poor health outcomes. Little is known about how older adults who live alone experience the process of receiving a diagnosis of mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Objective: The aim of this study was to understand the effects and meanings of receiving a diagnosis of MCI or AD on the lived experience of older adults living alone. Methods: This is a qualitative study of adults age 65 and over living alone with cognitive impairment. Participants’ lived experiences …were elicited through ethnographic interviews and participant observation in their homes. Using a qualitative content analysis approach, interview transcripts and fieldnotes were analyzed to identify codes and themes. Results: Twenty-nine older adults and 6 members of their social circles completed 114 ethnographic interviews. Core themes included: relief, distress, ambiguous recollections, and not knowing what to do. Participants sometimes felt uplifted and relieved by the diagnostic process. Some participants did not mention having received a diagnosis or had only partial recollections about it. Participants reported that, as time passed, they did not know what to do with regard to the treatment of their condition. Sometimes they also did not know how to prepare for a likely worsening of their condition, which they would experience while living alone. Conclusion: Findings suggest the need for more tailored care and follow-up as soon as MCI or AD is diagnosed in persons living alone. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, diagnosis, health services, residence characteristics

DOI: 10.3233/JAD-170723

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1517-1529, 2018

Authors: Paley, Elena L. | Merkulova-Rainon, Tatiana | Faynboym, Aleksandr | Shestopalov, Valery I. | Aksenoff, Igor

Article Type: Research Article

Abstract: Earlier we reported induction of neurotoxicity and neurodegeneration by tryptophan metabolites that link the metabolic alterations to Alzheimer’s disease (AD). Tryptophan is a product of the Shikimate pathway (SP). Human cells lack SP, which is found in human gut bacteria exclusively using SP to produce aromatic amino acids (AAA). This study is a first attempt toward gene-targeted analysis of human gut microbiota in AD fecal samples. The oligonucleotide primers newly-designed for this work target SP-AAA in environmental bacteria associated with human activity. Using polymerase chain reaction (PCR), we found unique gut bacterial sequence in most AD patients (18 of 20), …albeit rarely in controls (1 of 13). Cloning and sequencing AD-associated PCR products (ADPP) enables identification of Na(+)-transporting NADH: Ubiquinone reductase (NQR) in Clostridium sp. The ADPP of unrelated AD patients possess near identical sequences. NQR substrate, ubiquinone is a SP product and human neuroprotectant. A deficit in ubiquinone has been determined in a number of neuromuscular and neurodegenerative disorders. Antibacterial therapy prompted an ADPP reduction in an ADPP-positive control person who was later diagnosed with AD-dementia. We explored the gut microbiome databases and uncovered a sequence similarity (up to 97%) between ADPP and some healthy individuals from different geographical locations. Importantly, our main finding of the significant difference in the gut microbial genotypes between the AD and control human populations is a breakthrough. Show more

Keywords: Alzheimer’s disease, bacterial enzyme sequence, environmental stool samples, human gut microbiota, PCR testing

DOI: 10.3233/JAD-170764

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1531-1540, 2018

Authors: Wang, Hua | Stewart, Tessandra | Toledo, Jon B. | Ginghina, Carmen | Tang, Lu | Atik, Anzari | Aro, Patrick | Shaw, Leslie M. | Trojanowski, John Q. | Galasko, Douglas R. | Edland, Steven | Jensen, Poul H. | Shi, Min | Zhang, Jing | for The Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) features a dynamic sequence of amyloid deposition, neurodegeneration, and cognitive impairment. A significant fraction of AD brains also displays Lewy body pathology, suggesting that addition of classically Parkinson’s disease-related proteins to the AD biomarker panel may be of value. To determine whether addition of cerebrospinal fluid (CSF) total α-synuclein and its form phosphorylated at S129 (pS129) to the AD biomarker panel [Amyloid-β1-42 (Aβ42 ), tau, and phosphorylated tau (p-tau181 )] improves its performance, we examined CSF samples collected longitudinally up to 7 years as part of the Alzheimer’s Disease Neuroimaging Initiative. From 87 AD, 177 mild cognitive …impairment (MCI), and 104 age-matched healthy controls, 792 baseline and longitudinal CSF samples were tested for total α-synuclein, pS129, Aβ42 , tau, and p-tau181 . pS129, but not total α-synuclein, was weakly associated with diagnosis at baseline when t-tau/Aβ42 was included in the statistical model (β= 0.0026, p  = 0.041, 95% CI [(0.0001)–(0.005)]). CSF α-synuclein predicted Alzheimer’s Disease Assessment Scale-Cognitive (β= –0.59, p  = 0.0015, 95% CI [(–0.96)–(–0.23)]), memory (β= 0.4, p  = 0.00025, 95% CI [(0.16)–(0.59)]), and executive (0.62,<0.0001, 95% CI [(0.31)–(0.93)]) function composite scores, and progression from MCI to AD (β= 0.019, p  = 0.0011, 95% CI [(0.002)–(0.20)]). pS129 was associated with executive function (β= –2.55, p  = 0.0085, 95% CI [(–4.45)–(–0.66)]). Lower values in the mismatch between α-synuclein and p-tau181 predicted faster cognitive decline (β= 0.64, p  = 0.0012, 95% CI [(0.48)–(0.84)]). Longitudinal biomarker changes did not differ between groups, and may not reflect AD progression. The α-synuclein-p-tau181 -Mismatch could better predict longitudinal cognitive changes than classical AD markers alone, and its pathological correlates should be investigated further. Show more

Keywords: α-synuclein, Alzheimer’s disease, biomarkers, cerebrospinal fluid, mild cognitive impairment, pS129-α-synuclein

DOI: 10.3233/JAD-171013

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1541-1553, 2018

Authors: Grassi, Massimiliano | Perna, Giampaolo | Caldirola, Daniela | Schruers, Koen | Duara, Ranjan | Loewenstein, David A.

Article Type: Research Article

Abstract: Background: Available therapies for Alzheimer’s disease (AD) can only alleviate and delay the advance of symptoms, with the greatest impact eventually achieved when provided at an early stage. Thus, early identification of which subjects at high risk, e.g., with MCI, will later develop AD is of key importance. Currently available machine learning algorithms achieve only limited predictive accuracy or they are based on expensive and hard-to-collect information. Objective: The current study aims to develop an algorithm for a 3-year prediction of conversion to AD in MCI and PreMCI subjects based only on non-invasively and effectively collectable predictors. …Methods: A dataset of 123 MCI/PreMCI subjects was used to train different machine learning techniques. Baseline information regarding sociodemographic characteristics, clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy was used to extract 36 predictors. Leave-pair-out-cross-validation was employed as validation strategy and a recursive feature elimination procedure was applied to identify a relevant subset of predictors. Results: 16 predictors were selected from all domains excluding sociodemographic information. The best model resulted a support vector machine with radial-basis function kernel (whole sample: AUC = 0.962, best balanced accuracy = 0.913; MCI sub-group alone: AUC = 0.914, best balanced accuracy = 0.874). Conclusions: Our algorithm shows very high cross-validated performances that outperform the vast majority of the currently available algorithms, and all those which use only non-invasive and effectively assessable predictors. Further testing and optimization in independent samples will warrant its application in both clinical practice and clinical trials. Show more

Keywords: Alzheimer’s disease, clinical prediction rule, machine learning, mild cognitive impairment, personalized medicine

DOI: 10.3233/JAD-170547

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1555-1573, 2018

Authors: Tucholka, Alan | Grau-Rivera, Oriol | Falcon, Carles | Rami, Lorena | Sánchez-Valle, Raquel | Lladó, Albert | Gispert, Juan Domingo | Molinuevo, José Luis | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Gray matter changes associated with the progression of Alzheimer’s disease (AD) have been thoroughly studied. However, alterations in white matter tracts have received less attention, particularly during early or preclinical stages of the disease. Objective: To identify the structural connectivity changes across the AD continuum. Methods: We performed probabilistic tractography in a total of 183 subjects on two independent samples that include control (n  = 68) and preclinical AD individuals (n  = 28), patients diagnosed with mild cognitive impairment (MCI) due to AD (n  = 44), and AD patients (n  = 43). We compared the connectivity between groups, and …with CSF Aβ42 and tau biomarkers. Results: We observed disconnections in preclinical individuals, mainly located in the temporal lobe. This pattern of disconnection spread to the parietal and frontal lobes at the MCI stage and involved almost all the brain in AD. These findings were not driven by gray matter atrophy. Discussion: Using tractography, we were able to identify white matter changes between subsequent disease stages and, notably, also in preclinical AD. Therefore, this method may be useful for detecting early and specific brain structural changes during preclinical AD stage. Show more

Keywords: Alzheimer’s disease, biomarkers, connectivity, diffusion MRI, magnetic resonance imaging, mild cognitive impairment, preclinical stage, tractography

DOI: 10.3233/JAD-170553

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1575-1587, 2018

Authors: Fernando, W.M.A.D. Binosha | Rainey-Smith, Stephanie R. | Gardener, Samantha L. | Villemagne, Victor L. | Burnham, Samantha C. | Macaulay, S. Lance | Brown, Belinda M. | Gupta, Veer Bala | Sohrabi, Hamid R. | Weinborn, Michael | Taddei, Kevin | Laws, Simon M. | Goozee, Kathryn | Ames, David | Fowler, Christopher | Maruff, Paul | Masters, Colin L. | Salvado, Olivier | Rowe, Christopher C. | Martins, Ralph N. | For the AIBL Research Group

Article Type: Research Article

Abstract: Accumulating evidence suggests a diet high in protein and fiber may confer some protection against Alzheimer’s disease (AD). However, no human studies to-date have assessed the relationship between protein and fiber intake, and plasma and brain amyloid-β (Aβ). Consequently, this cross-sectional study, investigated the association of self-reported dietary intakes of protein and fiber, with plasma and brain Aβ burden (n  = 541, and n  = 162 respectively), in a well-characterized cohort of cognitively normal older adults, drawn from the larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. We observed 12.59 and 8.43 higher odds of ‘high’ brain Aβ burden (PiB …PET SUVR≥1.5) if protein intake fell in the lowest and middle tertile, respectively, compared to the highest tertile (p  = 0.008; p  = 0.013). Thus, in this cohort, the more protein consumed, the less likelihood of ‘high’ Aβ burden in the brain. No other significant associations were observed. The results of this study highlight the potentially protective impact of high dietary protein intake on brain Aβ burden in older adults, before objective memory decline is apparent. While longitudinal validation is required, these findings may assist in the development of dietary approaches aimed at preventing or delaying AD onset. Show more

Keywords: Alzheimer’s disease, amyloid-β, dietary fiber, dietary protein, PiB PET

DOI: 10.3233/JAD-170742

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1589-1598, 2018

Authors: Pedrinolla, Anna | Venturelli, Massimo | Fonte, Cristina | Munari, Daniele | Benetti, Maria Vittoria | Rudi, Doriana | Tamburin, Stefano | Muti, Ettore | Zanolla, Luisa | Smania, Nicola | Schena, Federico

Article Type: Research Article

Abstract: Background: Although current literature has shown that patients with Alzheimer’s disease (AD) have worse locomotion compared with healthy counterparts, no studies have focused on the efficacy of exercise training in improving gait abnormalities including biomechanics and metabolic aspects, in this population. Objective: To verify the effectiveness of exercise training (ET) on gait parameters (i.e., speed, step and stride length, single and double support, and energy cost of walking (Cw)) in patients with AD with respect to a standard cognitive treatment (CT). Methods: In this study, we included a small portion of data belonging to a larger …study (ClinicalTrials.gov number, NCT03034746). Patients with AD (Mini-Mental State Examination 22±5) were included in the study. Gait parameters and Cw were assessed at baseline and after 6 months (72 treatment sessions) of treatment. ET included 90 min of aerobic and strength training. CT included 90 min of cognitive stimuli. Results: The 16 patients assigned to ET exhibited significant improvement of Cw (–0.9±0.1 J/kg·m- 1), while differences in gait parameters were negligible. The effect on gait parameters were undetectable in the 18 patients assigned to CT (–0.2±0.5 J/kg·m-1 ). Conclusions: Data from this study showed that ET program seems effective in improving Cw in patients with AD. Interestingly, the positive effect of ET on Cw was not coupled with ameliorations of patient’s gait parameters, suggesting that the gain of metabolic aspects of locomotion were the main factors responsible for this positive result. Show more

Keywords: Dementia, energy cost of walking, physical activity, spatio-temporal gait parameters

DOI: 10.3233/JAD-170625

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1599-1609, 2018

Authors: Feng, Xueyan | Zhou, Aihong | Liu, Zhixin | Li, Fangyu | Wei, Cuibai | Zhang, Guili | Jia, Jianping

Article Type: Research Article

Abstract: Background: Delayed Matching-to-Sample Task 48 (DMS48), a brief tool measuring visual recognition memory, is valid to identify the early stage of Alzheimer’s disease (AD) in Caucasians. However, little data is available in Chinese. Objective: To develop norms and optimal cutoff points for the DMS48 in Chinese elders. Methods: A cross-sectional study was conducted in seven memory clinics from five cities across China. DMS48 was applied to 369 Chinese aged 50 or older (138 cognitively normal [CN], 112 mild cognitive impairment due to AD (MCI-A), and 119 mild AD dementia). The demographic factors which influence DMS48 scores …were investigated and the norms were established considering those factors. Receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff points. Results: Age was shown to influence DMS48 scores (r  = –0.36, p  < 0.05), and we presented the age-stratified normative data for the DMS48. The optimal cutoff point is 42/43 for identifying cognitive impairment (MCI-A and AD dementia) against CN (sensitivity 97.80% and specificity 89.13%) and MCI-A against CN (sensitivity 86.60% and specificity 94.20%). A cutoff of 39/40 obtained good sensitivity (100.00%) and specificity (94.90%) in discriminating AD dementia from CN. The age-stratified optimal cutoff points for identifying MCI-A were 43/44 for individuals aged 50 to 59 years old, 42/43 for 60 to 69 years old, 41/42 for 70 to 79 years old, and 40/41 for 80 or older, respectively (sensitivity 84.80% and specificity 95.70%). Conclusion: This study proved that DMS48 is of good validation in screening MCI-A in elderly Chinese. Show more

Keywords: Alzheimer’s disease, Delayed Matching-to-Sample Task 48, dementia, mild cognitive impairment, visual memory

DOI: 10.3233/JAD-170530

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1611-1618, 2018

Authors: Ishikawa, Masatsune | Yamada, Shigeki | Yamamoto, Kazuo

Article Type: Research Article

Abstract: Background: Dilated perivascular spaces in the centrum semiovale (CSO-PVS) are closely related to small vessel disease. However, recent studies have revealed that cerebral amyloid angiopathy can cause dilation of the CSO-PVS and obstruction of interstitial fluid flow along the intramural periarterial drainage. Objective: To examine the severity and age-related prevalence of CSO-PVS through magnetic resonance imaging (MRI) and investigate their clinically relevant factors. Methods: This study included 1,060 subjects who participated in our brain program. The subjects ranged from 23 to 83 years in age and were active in society. The frequencies of the MRI abnormalities …of small vessel diseases, including CSO-PVS, were examined. The CSO-PVS severity was classified into three grades: G0, G1, G2, according to the visual rating. The subjects were divided into five age groups and their age-related frequencies were also studied. Using the clinico-laboratory data of 712 subjects, the clinically relevant factors of CSO-PVS were investigated using logistic regression analysis. Results: The frequencies of all G0 (“normal”) MRI abnormalities significantly decreased with age. A high prevalence of G2 CSO-PVS was observed (24%) in the youngest group aged≤39 years, whereas other MRI abnormalities in this group were not or rarely observed. In multivariable logistic regression analyses, G2 CSO-PVS was found to be closely associated with age, hypertension, and the estimated glomerular filtration ratio. Conclusions: This study reveals that CSO-PVS begin to develop in subjects aged less than 39 years. Age-related changes are involved. Further studies are necessary to elucidate the pathophysiological role of the CSO-PVS. Show more

Keywords: Aging, cerebral amyloid angiopathy, dementia, interstitial fluid, magnetic resonance imaging, small vessel disease, white matter

DOI: 10.3233/JAD-170755

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1619-1626, 2018

Authors: François, Mathilde | Sicsic, Jonathan | Pelletier Fleury, Nathalie

Article Type: Research Article

Abstract: Background: The impact of adverse effects of drugs for dementia on the risk of hospitalization has not been much studied despite the impact of hospitalizations on cognitive decline. Objective: To determine if the main adverse effects of cholinesterase inhibitors and memantine may be associated with excess of hospitalization and to quantify the subsequent impact on healthcare expenditures. Methods: A representative sample of the French national health insurance beneficiaries aged 65 and older and suffering from dementia were included and followed from 2007 to 2014. Binary logit models for longitudinal data (GEE estimation technique) were used to …estimate the excess of hospitalization events related to the adverse effects of anti-dementia drugs and then to derive the additional costs of hospitalizations for the public health insurance fund. Results: In total, 7,668 patients were followed, generating 111,133 individual observations over the 8-year period. Treated patients were hospitalized significantly more than non-treated patients (adjusted Odd Ratio (OR) = 1.08, 95% confidence interval (95% CI) = [1.02 to 1.13], p  = 0.004), mainly with cholinesterase inhibitors for cardiac (OR = 1.21, 95% CI = [1.01 to 1.46], p  = 0.034) and gastrointestinal events (OR = 1.43, 95% CI = [1.01–2.05], p  = 0.045), especially with rivastigmine. When extrapolated to the entire population, this corresponded to an annual additional cost of € 55,000. Conclusion: Prescription of antidementia drugs, more specifically rivastigmine, increases the risk of hospitalizations via their cardiac and gastrointestinal adverse effects and lead to additional health care expenditures. Even though these results must be confirmed, they may encourage cautious consideration of the balance between benefits and harms before a prescription is given. Show more

Keywords: Adverse effects, cholinesterase inhibitors, dementia, hospitalization, medical overuse, memantine

DOI: 10.3233/JAD-170371

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1627-1637, 2018

Authors: Redston, Mitchell R. | Hilmer, Sarah N. | McLachlan, Andrew J. | Clough, Alexander J. | Gnjidic, Danijela

Article Type: Research Article

Abstract: Background: Older people with cognitive impairment, including dementia and delirium, are high users of acute care services internationally. Potentially inappropriate medication (PIM) use may be associated with adverse outcomes, including hospital re-admission, functional disability, and mortality. Objective: This systematic review aimed to quantify and compare the prevalence of PIMs in older inpatients with and without cognitive impairment. Methods: A systematic search of observational studies was performed independently assessed by two reviewers in Embase, Medline, PsycINFO, International Pharmaceutical Abstracts, Scopus, and Informit. Articles published in English during the period January 2007–June 2017 that reported PIM prevalence in …hospital inpatients ≥ 65 years were included. PIMs were defined as the presence of polypharmacy (multiple medication use) and using implicit or explicit tools, such as the Beers criteria, and ‘Screening Tool of Older Person ’s Prescriptions ’ (STOPP). Results: 47 articles were included. In studies measuring polypharmacy (n  = 15), the prevalence of PIMs ranged from 53.2% to 89.8% and 30.4% to 97.1% for inpatients with and without cognitive impairment, respectively, and 24.0% to 80.0% when cognitive status was unreported. In studies employing explicit and implicit tools (n  = 35), the prevalence of PIMs when cognitive impairment was reported ranged from 20.6% to 80.5% using the Beers criteria, and 39.3% to 88.5% using STOPP. When cognitive status was unreported, the prevalence of PIMs ranged from 7.0% to 79.2% using the Beers criteria, and 20.0% to 63.4% using STOPP. Conclusion: Our findings suggest a high prevalence of PIMs in older inpatients with and without cognitive impairment. Future studies should investigate the impact of PIM use on patient-centered outcomes, such as functional status and quality of life, to inform enhanced acute care services. Show more

Keywords: Cognitive impairment, dementia, hospitalization, older people, polypharmacy, potentially inappropriate medications (PIMs), prevalence

DOI: 10.3233/JAD-170842

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1639-1652, 2018

Authors: Suzuki, Ayuko | Shinozaki, Jun | Yazawa, Shogo | Ueki, Yoshino | Matsukawa, Noriyuki | Shimohama, Shun | Nagamine, Takashi

Article Type: Research Article

Abstract: Background: The mental rotation task is well-known for the assessment of visuospatial function; however, it has not been used for screening of dementia patients. Objective: The aim of this study was to create a simple screening test for patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) by focusing on non-amnestic symptoms. Methods: Age-matched healthy controls (age 75.3±6.8), patients with MCI (76.5±5.5), and AD (78.2±5.0) participated in this study. They carried out mental rotation tasks targeting geometric graphics or alphabetical characters with three rotating angles (0°, 90°, and 180°) and indicated the correct answer. Response …accuracy and reaction time were recorded along with their eye movements using an eye tracker. To quantify their visual processing strategy, the run count ratio (RC ratio) was calculated by dividing the mean number of fixations in incorrect answers by that in correct answers. Results: AD patients showed lower accuracy and longer reaction time than controls. They also showed a significantly greater number of fixation and smaller saccade amplitude than controls, while fixation duration did not differ significantly. The RC ratio was higher for AD, followed by MCI and control groups. By setting the cut-off value to 0.47 in the 180° rotating angle task, we could differentiate MCI patients from controls with a probability of 80.0%. Conclusions: We established a new screening system for dementia patients by evaluating visuospatial function. The RC ratio during a mental rotation task is useful for discriminating MCI patients from controls. Show more

Keywords: Alzheimer’s disease, cognition, early diagnosis, eye movement, mild cognitive impairment

DOI: 10.3233/JAD-170801

Citation: Journal of Alzheimer's Disease, vol. 61, no. 4, pp. 1653-1665, 2018