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An increasing number of systematic reviews and meta-analyses have been published on the association between oral health and cognitive dysfunction, also known as oral-cognitive links. However, there is great diversity in the oral and cognitive factors included in these studies, with different opinions for clinical practice drawn from the evidence. To understand which oral and cognitive factors are involved in those associations, we conducted an umbrella review of 28 systematic reviews, including 12 meta-analyses, on oral-cognitive links. We found that (a) periodontal diseases, oral microbiome, and dementia were frequently studied, while other factors, such as mastication and mild cognitive impairment, were less commonly investigated, and (b) severe deterioration of oral health, such as severe periodontitis or extensive tooth loss, rather than the presence of oral diseases alone, was strongly associated with cognitive dysfunction. In conclusion, the diversity of oral and cognitive factors included in the review studies reflects the complexity of oral-cognitive links. Clarifying the factors helps to form evidence-based clinical advice for healthcare., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Subjects with comorbidities are at risk for neurodegeneration. There is a lack of a direct relationship between comorbidities and neurodegeneration. In this study, immunomagnetic reduction (IMR) assays were utilized to assay plasma Aβ 1-42 and total tau protein (T-Tau) levels in poststroke (PS, n = 27), family history of Alzheimer's disease (ADFH, n = 35), diabetes (n = 21), end-stage renal disease (ESRD, n = 41), obstructive sleep apnea (OSA, n = 20), Alzheimer's disease (AD, n = 65). Thirty-seven healthy controls (HCs) were enrolled. The measured concentrations of plasma Aβ 1-42 were 14.26 ± 1.42, 15.43 ± 1.76, 15.52 ± 1.60, 16.15 ± 1.05, 16.52 ± 0.59, 15.97 ± 0.54 and 20.06 ± 3.09 pg/mL in HC, PS, ADFH, diabetes, ESRD, OSA and AD groups, respectively. The corresponding concentrations of plasma T-Tau were 15.13 ± 3.62, 19.29 ± 8.01, 17.93 ± 6.26, 19.74 ± 2.92, 21.54 ± 2.72, 20.17 ± 2.77 and 41.24 ± 14.64 pg/mL. The plasma levels of Aβ 1-42 and T-Tau in were significantly higher in the PS, ADFH, diabetes, ESRD and OSA groups than controls (Aβ 1-42 in PS: 15.43 ± 1.76 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.005; T-Tau in PS: 19.29 ± 8.01 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aβ 1-42 in ADFH: 15.52 ± 1.60 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ADFH: 17.93 ± 6.26 vs. 15.13 ± 3.62 pg/mL, p < 0.005, Aβ 1-42 in diabetes: 16.15 ± 1.05 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in diabetes: 19.74 ± 2.92 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aβ 1-42 in ESRD: 16.52 ± 0.59 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in ESRD: 21.54 ± 2.72 vs. 15.13 ± 3.62 pg/mL, p < 0.001, Aβ 1-42 in OSA: 15.97 ± 0.54 pg/mL vs. 14.26 ± 1.42 pg/mL, p < 0.001; T-Tau in OSA: 20.17 ± 2.77 vs. 15.13 ± 3.62 pg/mL, p < 0.001). This evidence indicates the high risk for dementia in these groups from the perspective of plasma biomarkers., (© 2022. The Author(s).)

Recent genetic progress allows the molecular diagnosis of young-onset dementia, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). We aimed to identify the mutational and clinical spectra of causal genes in a Taiwanese cohort of young-onset dementia. Ninety-one patients with young-onset dementia and 22 age/gender-matched controls were recruited. Genetic causes were identified by a targeted panel containing 90 causative genes for AD, FTD, and related neurodegenerative disorders. Plasma biomarkers, including total tau, Aβ42, and Aβ40, were assayed. Molecular amyloid and tau PET scans were performed in some patients carrying mutations. Nine of 52 patients (17.3%) with young-onset AD had mutations: 2 (22.2%), 4 (44.5%), 2 (22.2%), and 1 (11.1%) in APP, PSEN1, PSEN2, and TREM2, respectively. Two of 33 patients (6.1%) with young-onset FTD had mutations in MAPT and LRRK2. Three of the 6 patients (50.0%) with possible FTD combined with other neurodegenerative disorders had individual mutations in APP, PSEN2, or MAPT. Patients with PSEN1 mutations had earlier onset of disease than those without mutations (p = .02). Plasma level of total tau was increased and Aβ42 and Aβ40 levels decreased in all groups of dementia patients compared to controls. Our findings provide a genetic spectrum of young-onset dementia in our population., (© 2021 Wiley Periodicals LLC.)

Aim: We aimed to evaluate the long-term risk of dementia in patients with periodontitis and its associated factors., Materials and Methods: Using Taiwan's National Health Insurance Database, we identified 56,018 patients aged ≥50 years with newly diagnosed periodontitis in 2000-2008. A cohort of 56,018 adults without periodontitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident dementia was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia associated with periodontitis were calculated in the multivariate regressions., Results: Periodontitis was associated with dementia risk (HR: 1.79, 95% CI: 1.67-1.93), and the association between periodontitis and dementia risk was significant in men, women, and people aged more than 60 years. Among patients with periodontitis, the use of statins (HR: 0.78, 95% CI: 0.71-0.87), metformin (HR: 0.53, 95% CI: 0.44-0.62), and influenza vaccination (HR: 0.67, 95% CI: 0.61-0.74) were associated with a reduced risk of dementia, while diabetes, mental disorders, and stroke were major significant risk factors., Conclusions: Periodontitis was a risk factor for dementia, while the use of statins and metformin may reduce the risk of dementia., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Blood-based biomarker assays of plasma β-amyloid (Aβ) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aβ 1-42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aβ 1-42  × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: many people living with dementia remain underdiagnosed and unrecognised. Screening strategies are important for early detection., Objective: to examine whether the Lawton's Instrumental Activities of Daily Living (IADL) scale, compared with other cognitive screening tools-the Mini-Mental State Examination (MMSE), and the Ascertain Dementia 8-item Informant Questionnaire (AD8)-can identify older (≥ 65 years) adults with dementia., Design: population-based cross-sectional observational study., Setting: all 19 counties in Taiwan., Participants: community-dwelling older adults (n = 10,340; mean age 74.87 ± 6.03)., Methods: all participants underwent a structured in-person interview. Dementia was identified using National Institute on Aging-Alzheimer's Association core clinical criteria for all-cause dementia. Receiver operator characteristic curves were used to determine the discriminant abilities of the IADL scale, MMSE and AD8 to differentiate participants with and without dementia., Results: we identified 917 (8.9%) participants with dementia, and 9,423 (91.1%) participants without. The discriminant abilities of the MMSE, AD8 and IADL scale (cutoff score: 6/7; area under curve = 0.925; sensitivity = 89%; specificity = 81%; positive likelihood ratio = 4.75; accuracy = 0.82) were comparable. Combining IADL with AD8 scores significantly improved overall accuracy: specificity = 93%; positive likelihood ratio = 11.74; accuracy = 0.92., Conclusions: our findings support using IADL scale to screen older community-dwelling residents for dementia: it has discriminant power comparable to that of the AD8 and MMSE. Combining the IADL and the AD8 improves specificity., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study aimed to identify lifestyle factors associated with cognitive change and to explore whether the effect of lifestyle varies by socioeconomic status (SES). Participants aged 65 years and older were recruited from elderly health checkup programs from 2011 to 2013 in Taiwan. Neuropsychological tests, including tests of global cognition, logical memory, executive function, verbal fluency and attention, were administered at baseline (N = 603) and 2 years later (N = 509). After literature review, 9 lifestyle factors and 3 SES indicators were chosen and their effects on cognitive change were evaluated using linear regression adjusting for age, sex, education, APOE ε4 status, and baseline cognitive score. Five lifestyle factors (high vegetable and fish intake, regular exercise, not smoking, and light to moderate alcohol consumption) and 3 SES indicators [annual household income (> 33,333 USD vs. less), occupational complexity (high vs. low mental demanding job), and years of education (> 12 years vs. less)] were found to be protective against cognitive decline (P < 0.1 in any cognitive domains, ß ranging from 0.06 to 0.38). After further adjusting for all the lifestyle and SES factors, fish intake, higher income and occupational complexity remained protective. Significant interactions were found between a healthful lifestyle (defined as having ≥ 3 healthful lifestyle factors) and income on changes of global cognition and verbal fluency (Pinteraction = 0.02 and 0.04). The protective effect of a healthful lifestyle was observed only among participants with lower income in global cognition and logical memory [ß = 0.17, 95% confidence interval (CI) = 0.07-0.26; ß = 0.30, 95% CI = 0.14-0.46]. To the best of our knowledge, this study for the first time explored how the interactions of lifestyle and SES affect cognitive change. Our findings will aid in developing dementia prevention programs and reduce health inequalities., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the risk of dementia in patients with stroke who did and did not receive acupuncture treatment., Design: Retrospective cohort study., Setting: This study was based on Taiwan's National Health Insurance Research Database that included patients with stroke hospitalised between 1 January 2000 and 31 December 2004., Participants: We identified 11 220 patients aged 50 years and older with newly diagnosed stroke hospitalisation., Primary and Secondary Outcome Measures: We compared the incident dementia during the follow-up period until the end of 2009 in patients with stroke who did and did not receive acupuncture. The adjusted HRs and 95% CIs of dementia associated with acupuncture were calculated in multivariate Cox proportional hazard regressions., Results: Acupuncture treatment was associated with a decreased risk of dementia with multivariate adjustment (HR, 0.73; 95% CI 0.66 to 0.80), and the association was significant in both sexes and every age group, as well as in groups with ischaemic stroke, with fewer medical conditions and those hospitalised after stroke. Patients with stroke received acupuncture treatment, and conventional rehabilitation was associated with a significantly reduced risk of poststroke dementia (HR, 0.64; 95% CI 0.56 to 0.74)., Conclusions: This study raises the possibility that patients with non-haemorrhagic stroke who received acupuncture had a reduced risk of dementia. The results suggest the need for prospective sham-controlled and randomised trials to establish the efficacy of acupuncture in preventing dementia., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Comorbid medical diseases are highly prevalent in the geriatric population, imposing hardship on healthcare services for demented individuals. Dementia also complicates clinical care for other co-existing medical conditions. This study investigated the comorbidities associated with dementia in the elderly population aged 65 years and over in Taiwan., Methods: We conducted a nationwide, population-based, cross-sectional survey; participants were selected by computerized random sampling from all 19 Taiwan counties between December 2011 and March 2013. After exclusion of incomplete or erroneous data, 8,456 subjects were enrolled. Of them, 6,183 were cognitively normal (control group), 1,576 had mild cognitive impairment (MCI), and 697 had dementia. We collected information about types of comorbidities (i.e., vascular risk factors, lung diseases, liver diseases, gastrointestinal diseases, and cancers), Charlson comorbidity index score, and demographic variables to compare subjects with normal cognition, MCI, and dementia., Results: Regardless of the cognitive condition, over 60% of the individuals in each group had at least one comorbid disease. The proportion of subjects possessing at least three comorbidities was higher in those with cognitive impairment (MCI 20.9%, dementia 27.3%) than in control group (15%). Hypertension and diabetes mellitus were the most common comorbidities. The mean number of comorbidities and Charlson comorbidity index score were greater in MCI and dementia groups than in control group. Logistic regression demonstrated that the comorbidities significantly associated with MCI and dementia were cerebrovascular disease (OR 3.35, CI 2.62-4.28), cirrhosis (OR 3.29, CI 1.29-8.41), asthma (OR 1.56, CI 1.07-2.27), and diabetes mellitus (OR 1.24, CI 1.07-1.44)., Conclusion: Multiple medical comorbid diseases are common in older adults, especially in those with cognitive impairment. Cerebrovascular disease, cirrhosis, asthma, and diabetes mellitus are important contributors to cognitive deterioration in the elderly. Efforts to lower cumulative medical burden in the geriatric population may benefit cognitive function.

Background: Evidence of an association between lifestyle and marital status and risk of dementia is limited in Asia., Methods: In this nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 counties in Taiwan. A total of 10432 residents were assessed by a door-to-door in-person survey, among whom 7035 were normal and 929 were diagnosed with dementia using the criteria recommended by National Institute on Aging-Alzheimer's Association. Premorbid lifestyle habits and demographic data including marital status were compared between normal subjects and participants with dementia., Results: After adjustment for age, gender, education, body mass index, smoking, drinking, marital status, sleep habits, exercise, social engagement and co-morbidities including hypertension, diabetes and cerebrovascular diseases, an increased risk for dementia was found in people with widow or widower status (OR 1.42, 95% CI 1.15-1.77) and people who used to take a nap in the afternoon (OR 1.33, 95% CI 1.02-1.72). Decreased risk was found in people with the habit of regular exercise (OR 0.12, 95% CI 0.09-0.16), adequate night sleep (OR 0.55, 95% CI 0.39-0.76) and regular social engagement (OR 0.53, 95% CI 0.36-0.77)., Conclusions: Our results provide preliminary evidence of possible risk-reduction effects for dementia, including regular exercise even in modest amounts, social engagement and adequate night sleep, whereas people with the widow/widower status or who used to take an afternoon nap might have increased risk of dementia.

Introduction: Religious affiliations vary across ethnic groups because of different cultural backgrounds. Some studies have explored the association between religious affiliation and cognitive decline. Only a small portion of patients with cognitive decline progress to dementia. However, the association between religious affiliation and dementia risk remains unclear., Methods: In this case-control study, we recruited 280 patients with Alzheimer's disease (AD) and 138 with vascular dementia (VaD) (both aged ≥60 years) from three teaching hospitals in northern Taiwan between 2007 and 2010. Age-matched healthy controls (n=466) were recruited from an elderly health checkup program and from volunteers visiting the hospital during the same period. Three religious affiliations-Taoism, Buddhism, and Christianity-were evaluated. The study also assessed the effect of important factors such as gender or leisure activities on the association of religious affiliation with dementia risk., Results: Participants with Christianity affiliation showed decreased AD risk (adjusted odds ratio [AOR]=0.46, 95% confidence interval [CI]=0.25-0.87) compared with those without any religious affiliation. Moreover, this effect was stronger in women (AOR=0.38, 95% CI=0.15-0.92) and in participants who exercised regularly (>3 times/week; AOR=0.33, 95% CI=0.14-0.77). No significant association was observed among participants with Taoism and Buddhism affiliations. Affiliation to none of the religions was associated with VaD risk., Conclusions: Thus, Chinese participants having Christianity affiliation showed decreased AD risk. Moreover, the protective effect was more evident in women and in participants who exercised regularly., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

An increasing population of dementia patients produces substantial societal impacts. We assessed the prevalence of mild cognitive impairment (MCI) and all-cause dementia, including very mild dementia (VMD), in Taiwan. In a nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 Taiwan counties and were enrolled between December 2011 and March 2013. Cases were identified through in-person interviews based on the National Institute on Aging-Alzheimer's Association clinical criteria. Demographic data and histories involving mental status and function in daily living were collected. The principal objective assessments were the Taiwanese Mental Status Examination and Clinical Dementia Rating. In all, 10,432 people aged 65 years or older (mean age 76.2 ± 6.7, 52.3% women) were interviewed. The age-adjusted prevalence of all-cause dementia was 8.04% (95% CI 7.47-8.61), including a 3.25% (95% CI 2.89-3.61) prevalence of VMD; that of MCI was 18.76% (95% CI 17.91-19.61). Women had a higher prevalence than men of both all-cause dementia (9.71% vs. 6.36%) and MCI (21.63% vs. 15.57%). MCI affects a considerable portion of the population aged 65 and above in Taiwan. The inclusion of VMD yields dementia prevalence rates higher than those previously reported from Taiwan. Old age, female gender, and a low educational level are significant associated factors.

Background: Dementia patients often present with coexisting medical conditions and potentially face higher risk of complications during hospitalization. Because the general features of postoperative adverse outcomes among surgical patients with dementia are unknown, we conducted a nationwide, retrospective cohort study to characterize surgical complications among dementia patients compared with sex- and age-matched nondementia controls., Methods: Reimbursement claims from the Taiwan National Health Insurance Research Database were studied. A total of 18,923 surgical patients were enrolled with preoperative diagnosis of dementia for 207,693 persons aged 60 years or older who received inpatient major surgeries between 2004 and 2007. Their preoperative comorbidities were adjusted and risks for major surgical complications were analyzed., Results: Dementia patients who underwent surgery had a significantly higher overall postoperative complication rate, adjusted odds ratio (OR) 1.79 (95 % confidence interval [CI] 1.72-1.86), with higher medical resources use, and in-hospital expenditures. Compared with controls, dementia patients had a higher incidence of certain postoperative complications that are less likely to be identified in their initial stage, such as: acute renal failure, OR = 1.32 (1.19-1.47); pneumonia, OR = 2.18 (2.06-2.31); septicemia, OR = 1.8 (1.69-1.92); stroke, OR = 1.51 (1.43-1.6); and urinary tract infection, OR = 1.62 (1.5-1.74)., Conclusions: These findings have specific implications for postoperative care of dementia patients regarding complications that are difficult to diagnose in their initial stages. Acute renal failure, pneumonia, septicemia, stroke, and urinary tract infection are the top priorities for prevention, early recognition, and intervention of postoperative complications among surgical patients with dementia. Further efforts are needed to determine specific protocols for health care teams serving this population.

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal-related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus.

White matter damage and its contribution to clinical manifestations in patients with dementia have been increasingly recognized. To explore white matter changes in different types of dementia, we examined brain water diffusivity with diffusion tensor imaging (DTI). We measured fractional anisotropy and mean diffusivity of multiple white matter regions in patients with amnesic mild cognitive impairment (MCI, n=10), Alzheimer's disease (AD, n=30), subcortical ischemic vascular dementia (SIVD, n=18), frontotemporal dementia (FTD, n=7), and control subjects (n=20). We performed pairwise comparisons in each region of interest between patients and controls. MCI patients showed diffusion tensor change (DTC) in the left anterior periventricular (PV) area, possibly in the right posterior PV area, and the genu of the corpus callosum. AD patients showed DTC in the corpus callosum, and in frontal and parieto-occipital subcortical and anterior PV areas. In SIVD patients, DTC occurred in the genu of the corpus callosum, and in bilateral frontal subcortical and PV areas. FTD patients differed from controls in showing DTC in the temporal and frontal subcortical areas, the genu of the corpus callosum and PV areas. The degree of DTC correlated with the clinical severity of dementia as assessed by the clinical dementia rating (CDR). Mean diffusivity was diffusely and positively associated with the CDR scores. Fractional anisotropy of the PV areas was negatively associated with the CDR scores, suggesting a critical role of the lateral cholinergic pathways.

Background/aims: It is estimated that there are 90,000 patients with dementia in the 23 million habitants of Taiwan, with a few institutions specialized in dementia care. To assess the need of institutional care for dementia, we investigated the institution prevalence of dementia., Methods: We performed stratified randomized sampling of elder residents from different types of institutions in different regions of Taiwan. A 2-stage survey with screening and clinical confirmation was carried out in 2004., Results: In total, 1,525 residents aged 65 years and over in 60 institutions participated in the study in which 1,308 elders completed the 2-stage survey. Among these, 631 elders were diagnosed as having dementia. The dementia prevalence was 26.8% in the residential houses, 61.8% in the assisted living facilities and 64.5% in the nursing homes. Vascular dementia was the leading cause of dementia in the institutions. Old age, diabetes mellitus and family history of dementia increased risks for both Alzheimer's disease and vascular dementia., Conclusion: The investigation showed that the prevalence of dementia in the long-term care units of Taiwan was much higher than those from community studies and the high prevalence in the institutions depended on the type of the long-term care unit., (Copyright (c) 2007 S. Karger AG, Basel.)

Background/purpose: Although a deficit of semantic memory is evident in the dementia of the Alzheimer's type (DAT), the underlying neuropsychologic mechanism remains controversial. Breakdown of the semantic network during the course of DAT and an inability to access semantic information have been postulated as possible explanations, but supporting data are limited, particularly in low-educated patients. This study examined semantic memory in low-educated patients with different degrees of dementia severity., Methods: In total, 197 adult subjects were recruited, including 165 DAT patients and 32 normal controls. Subjects were divided into four subgroups according to their dementia severity. All subjects completed an episodic memory task, the Six-Object Memory Test, and semantic memory tasks including the Object Naming Test, the Remote Memory Test and the Semantic Association of Verbal Fluency Test. One-way ANOVA and ANCOVA with a post hoc Scheffe's procedure were used to evaluate differences between groups., Results: All patients, irrespective of the degree of dementia, showed impaired performance on the Six-Object Memory Test [F (4, 163) = 69.95, p < 0.0001 for immediate recall; F (4, 163) = 41.34, p < 0.0001 for delayed recall]. On the semantic memory tasks, patients with moderate to severe dementia showed impaired performances on the Object Naming Test [F (4, 180) = 28.25, p < 0.0001] and the Remote Memory Test [F (4, 167) = 26.22, p < 0.0001 for recall; F (4, 167) = 34.80, p < 0.0001 for recognition], while all patients performed defectively on the Semantic Association of Verbal Fluency Test [F (4, 194) = 70.43, p < 0.0001]., Conclusion: Our results thus partially support the hypotheses that a loss of semantic structure and an inability to access semantic knowledge occur in the pathogenesis of DAT.

Background/purpose: Behavioral and psychologic symptoms of dementia (BPSD) are major sources of a caregiver's burden and also the most important factor when considering the need for institutionalization of dementia patients. BPSD occur in about 90% of patients with dementia. Studies comparing the BPSD in the major types of dementia using unitary behavioral rating scales are limited. We studied BPSD in patients with four major types of dementias from a memory clinic., Methods: We recruited patients with dementia from our memory clinic from January 2003 to February 2004. The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) was used to measure BPSD severity. Clinical Dementia Rating and Mini Mental State Examination were used to determine dementia severity., Results: A total of 137 patients with four major types of dementia were recruited from 155 patients with dementia who attended the clinic during the study period. The main dementia types identified were Alzheimer's dementia (AD) in 54.8%, vascular dementia (VaD) in 20.6%, frontotemporal dementia (FTD) in 8.4%, dementia with Lewy bodies (DLB) in 4.5%, and other dementias in 11.6%. BPSD were found in 92.0% of the patients but only 43.1% received psychotropic treatment. The relative risk of receiving psychotropic treatment for BPSD subscales paralleled the extent of caregivers' burden as assessed by the BEHAVE-AD global rating. Type-specific BPSD, e.g. hallucination was identified for DLB, activity disturbances for FTD, anxiety and phobias for AD and affective disturbance for VaD., Conclusion: A strategy of targeting type-specific BPSD may be beneficial, such as environmental stimulus control for DLB patients who are prone to have hallucinations, design of a pacing path for patients with FTD who need support for symptoms of wandering and emotional support for patients with VaD who are susceptible to depression.

Objective: The Community Screening Instrument for Dementia (CSI-D) has been reported to be sensitive. The authors examined the reliability and validity of a Chinese (Taiwanese) version of the CSI-D for elderly patients., Methods: Four groups were tested with the CSI-D: 31 with mild or moderate dementia; 32 non-dementia, depressed subjects; and 34 low-education, and 30 high-education normal-comparison subjects. Patients with dementia or depression were selected from outpatients of two hospitals. Testing was carried out in either the community or outpatient setting., Results: The internal consistency, interrater reliability, and test-retest reliability of the CSI-D were good. The CSI-D was highly correlated with scores on the Mini-Mental State Examination and 10-word-list-learning task. Correlation with the Montgomery-Asberg Depression Rating Scale was not significant. Receiver Operating Characteristic analysis suggested that the CSI-D was a good instrument in differentiating dementia from depression and normal subjects with low education. It had good sensitivity and specificity. Education was related to the cognitive scores but not related to informant scores. The combination of an informant interview with a cognitive test enhanced the performance of the CSI-D., Conclusions: The Taiwan Chinese version of the CSI-D is psychometrically sound, brief, easy to complete, and therefore suitable as a screening instrument for dementia in Taiwan. The study reinforces earlier suggestions that the informant interview yields improved validity for detecting dementia.

IntroductionClinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown.MethodsWe included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier.ResultsBoth semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices.DiscussionThis study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers.HighlightsNoun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Background and objectivesMost primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants.MethodsThis study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors.ResultsAll PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively.DiscussionThe findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.

Objective Evaluating social-functioning impairments in patients with Alzheimer's disease (AD) objectively is essential for clinical service. However, the existing instruments lack representative content, consensus on purposes of use, and adequate scoring systems and samples. This study was thus to develop a social functioning scale for patients: the Social Functioning Scale for Alzheimer's Disease (SFSAD). Method Questionnaires were analyzed from 142 AD patients, 30 patients with amnestic mild cognitive impairment (aMCI), and 50 normal controls. Results Based on the literature review and experts' opinions, the final scale includes 20 items in four subscales. The SFSAD showed high internal consistency coefficients (Cronbach's α =.97) and test–retest reliability (r =.99) coefficients. The content validity was desirable, and the criterion-related validity was demonstrated by a significant association with the MMSE, the IADL, and the Barthel ADL. The discriminant validity of the scale was also demonstrated as the level of social-functioning impairment was significantly related to the degree of dementia, and for construct validity, our findings supported the structure of the four-factor hypothesized model. Conclusions The SFSAD is thus a practical, psychometrically sound, and easy-to-administer measure to evaluate social functioning of AD and aMCI in brisk clinical settings. [ABSTRACT FROM AUTHOR]

Background/purpose: Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI.Methods: Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30) and individuals with SMI (n = 61), aMCI-single domain (n = 24), aMCI-multiple domain (n = 33), or DAT (n = 35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations.Results: Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations.Conclusion: Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT. [ABSTRACT FROM AUTHOR]

Background/purpose: Leisure activities have been associated with a decreased risk of dementia. However, to date, no study has explored how apolipoprotein E (ApoE) e4 status or vascular risk factors modified the association between leisure activities and dementia risks.Methods: This case-control study recruited patients (age ≥ 60 years) with Alzheimer's disease (AD; n = 292) and vascular dementia (VaD; n = 144) and healthy controls (n = 506) from three teaching hospitals in Taiwan between 2007 and 2010. Information on patient's leisure activities were obtained through a questionnaire. Conditional logistic regression models were used to assess the association of leisure activities and ApoE e4 status with the risk of dementia.Results: High-frequency physical activity was associated with a decreased risk of AD [adjusted odds ratio (AOR) = 0.45], and the results become more evident among ApoE e4 carriers with AD (AOR = 0.30) and VaD (AOR = 0.26). Similar findings were observed for cognitive (AOR = 0.42) and social activities (AOR = 0.55) for AD. High-frequency physical, cognitive, and social activities were associated with a decreased risk of VaD (AOR = 0.29-0.60). Physical and social activities significantly interacted with each other on the risk of VaD (pinteraction = 0.04).Conclusion: Physical activity consistently protects against AD and VaD. Significant interactions were identified across different types of leisure activities in lowering dementia risk. [ABSTRACT FROM AUTHOR]

Background: CHRNA7 encodes the α7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response. Methods: Mild to moderate AD patients received ChEIs were recruited from the neurology clinics of three teaching hospitals from 2007 to 2010 (n = 204). Nine haplotype-tagging single nucleotide polymorphisms of CHRNA7 were genotyped. Cognitive responders were those showing improvement in the Mini-Mental State Examination score ≧2 between baseline and 6 months after ChEI treatment. Results: AD women carrying rs8024987 variants [GG+GC vs. CC: adjusted odds ratio (AOR) = 3.62, 95% confidence interval (CI) = 1.47–8.89] and GG haplotype in block1 (AOR = 3.34, 95% CI = 1.38–8.06) had significantly better response to ChEIs (false discovery rate <0.05). These variant carriers using galantamine were 11 times more likely to be responders than female non-carriers using donepezil or rivastigmine. Conclusion: For the first time, this study found a significant association between CHRNA7 polymorphisms and better ChEI response. If confirmed by further studies, CHRNA7 polymorphisms may aid in predicting ChEI response and refining treatment choice. [ABSTRACT FROM AUTHOR]

Blood-based biomarker assays of plasma β-amyloid (Aβ) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aβ 1–42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aβ 1–42 × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA. The figure demonstrates system and methods used in this report. In the upper part of the center, there is a SQUID-based magnetometer consisting of both excitation and pickup coils. The left upper part shows signals of the reagent before mixing the sample solution containing Aβ 1–40 , Aβ 1–42 and tau protein. The right upper part shows an example by mixing plasma sample from a control subject whose plasma sample containing relative low levels of the pathological proteins compared to the right lower part, which mixed plasma sample with higher levels from a subject with dementia due to Alzheimer's disease. After bindings of the molecules of the pathological proteins, the signals start to decline because of the spin velocities of the magnetic nanoparticles decreased resulting the signal reduction demonstrated in the lower part of the center. Left lower shows images of biofunctionalized nano-particles of a scanning electron microscope. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract: BMI change and BMI at an early age have not been investigated as risks for dementia. This case-control study included 286 dementia patients and 268 controls from two medical centers between 2007 and 2009. BMI information was collected from medical records and questionnaires. Men and women with low BMIs at the time of the study, in their 20s, and in their 40s had significantly increased risks of Alzheimer''s disease (AD) (odds ratio = OR = 2.62–3.97) and increased vascular dementia (VaD) risk (20s and 40s: OR = 6.23–11.11) compared with those with normal BMIs. High BMI in the 20s and 40s was associated with increased VaD risk (OR = 15.29 and 10.32) among women. For BMI changes from the 20s or 40s, the second and third tertiles were significantly associated with decreased AD risk among women (OR = 0.15–0.35) compared to the first tertile. The third tertile of BMI change from the 20s or 40s was associated with decreased VaD risk among women (OR = 0.06 and 0.14). Low BMIs in the 20s and 40s were stronger predictors of AD and VaD. There was a U-shaped association between BMI at different ages and dementia among participants with VaD. [Copyright &y& Elsevier]

Recent study has suggested semantic memory deterioration may be the earliest cognitive changes in Alzheimer's disease (AD). Few previous researchers have investigated specific changes in the semantic structures in the memory of patients with amnestic mild cognitive impairment (aMCI). This study examined the clustering performance in semantic fluency among 160 participants in various MCI subgroups (aMCI single domain, aMCI-sd, n = 30; aMCI multiple domain, aMCI-md, n = 30; non-aMCI multiple domain, naMCI-md, n = 10) as well as a group of mildly impaired individuals with dementia of AD type (DAT, n = 20), and a group of healthy controls (HC, n = 70). Compared with HC group, DAT patients presented deficient clustering in each semantic category related to living things. aMCI-sd group presented defective clustering when dealing with the clustering of items that may be more strongly associated with praxis and perceptual information in the categories that included inanimate living things. aMCI-md group displayed defective patterns similar to those in the aMCI-sd group; however, they displayed more profound deficits in clustering that may require perceptual information. Patients with naMCI-md preserved their ability to perform clustering on all of the categories. The poor clustering of items that may be more strongly associated with praxis could be used as a means of predicting conversion from aMCI-sd to DAT, whereas performance on items that may require perceptual information could be used to predict conversion among aMCI-md patients. These findings demonstrate the degree to which the semantic structures in memory can be used for the assessment of aMCI patients and prediction of conversion to DAT. • Semantic memory deficits may be earliest cognitive changes in Alzheimer's disease. • Structural changes in semantic memory in mild cognitive impairment are unclear. • Clustering performance discriminated mild cognitive impairment from normal aging. • Contents of semantic fluency are valuable in predicting dementia. [ABSTRACT FROM AUTHOR]