Questionable Dementia Research Articles

Dementia in People with Severe/Profound Intellectual (And Multiple) Disabilities, and Its Natural History

ABSTRACT Introduction Although the prevalence of dementia increases among people with severe/profound intellectual (and multiple) disabilities (SPI(M)D), dementia in people with SPI(M)D is not yet fully understood. Therefore, this study aimed to characterize the natural history of dementia in people with SPI(M)D, in particular, the prevalence and time of onset of dementia symptoms. Methods An explorative retrospective review of clinical records was conducted for people with SPI(M)D without dementia (n = 103), with questionable dementia (n = 19), and with diagnosed dementia (n = 19). Presence and time of onset of symptoms were extracted and compared between groups. Results People with questionable dementia or diagnosed dementia had compared to people without dementia more symptoms regarding the cognitive, activities of daily living, behavioral/psychological, and motor domains. The most prevalent early symptoms were memory loss, declined walking skills, increased anxious, apathetic, and irritable behavior. Predictors for dementia were the number of cognitive, behavioral/psychological, and motor symptoms. Conclusion These results contribute to enhance our understanding of dementia in people with SPI(M)D, which is essential for earlier recognizing and diagnosing dementia.

Blood DNA methylation biomarkers for cognitive decline in older adults with type 2 diabetes

AbstractBackgroundIndividuals with type 2 diabetes (T2D) are at particularly high risk for cognitive decline and dementia. Finding early, pre‐clinical biomarkers for detecting and tracking cognitive impairment and dementia in this population is important for personalized medicine approach. Our study aims to find blood DNA methylation biomarkers for cognitive decline among elderly T2D patients.MethodTwo groups of 30 T2D subjects each, from the Israel Diabetes and Cognitive Decline (IDCD) cohort, were included. One group (converters) was cognitively normal at baseline, yet at 36‐54 months follow‐up deteriorated from a Clinical Dementia Rating scale CDR = 0 (no dementia) to CDR≥0.5 (questionable dementia or frank dementia). The control group (non‐converters) was cognitively normal at baseline and maintained normal cognition during the follow‐up period (CDR = 0). We performed an epigenome‐wide association study, using the Illumina Infinium MethylationEPIC microarray, and searched for differentially methylated positions (DMPs) with significant methylation alterations (≥ 2 fold and FDR corrected p value <0.05) between the baseline and the follow‐up time points for each of the two groups.ResultParticipants were 65‐83 years of age (mean‐73.6 ± 4.1), 72% were men. The mean hemoglobin A1C value was 6.9 ± 0.8%, and T2D duration was 9.4 ± 4.7 years. Converters and non‐converters did not differ in any of these characteristics. Results show significant changes in multiple DMPs among the converters, but only in a few DMPs in the non‐converters. Gene ontology analyses indicates primarily involvement of central nervous system‐related pathways, mainly neurodevelopmental disorders.ConclusionThese preliminary results, employing a high‐throughput approach for methylation profile in blood, suggest methylomic alterations as a potential biomarker for cognitive decline in T2D elderly. A priori identification of patients at risk for cognitive decline may lead to early intervention in modifiable risk factors in this population, which is highly susceptible to dementia.

Hearing loss and dementia in Peruvian populations

AbstractBackgroundHearing loss is prevalent in older adults, affecting a third of this population. Hearing loss is a modifiable and treatable factor. It has been shown that hearing loss can lead to social isolation and later to dementia. In addition, the corresponding cortical area has a close relationship with auditory and cognitive processing. In this study we aimed to evaluate the association between dementia and hearing loss.MethodA multicenter cross‐sectional study was carried out in three locations of different altitude in Peru: Lima, Arequipa and Puno. Participants over 50 years of age with an available informant were recruited in memory clinics. The Hughes Clinical Dementia Rating (CDR) was employed to rate dementia (0 being healthy, 0.5 being questionable dementia, and greater than 1 being dementia). The exposure variable was reported hearing loss, which was defined as current hearing problems for more than six months. A descriptive analysis was performed and to evaluate the association between these variables, multinomial logistic regression with robust variances was used to estimate prevalence ratios (PR) with 95% confidence intervals.ResultsWe evaluated 295 patients. The mean age was 71.9 years. More than a half was female (68.8%). The prevalence of hearing loss was 19.6%. In the crude model, hearing loss were associated with increased prevalence of dementia, with older age and education being associated with higher and lower CDR scores, respectively. After adjusting for confounders and geographic clustering, the association between hearing loss and dementia showed a PR of 3.39 (95% CI: 1.11‐10.39) that in those without dementia.ConclusionIn our cohort of Peruvian participants, we found that hearing loss was associated with dementia in line with previous investigations. Further follow‐up studies are needed to better assess and characterize this association.

Cerebrospinal Fluid Neurofilament Light Predicts Risk of Dementia Onset in Cognitively Healthy Individuals and Rate of Cognitive Decline in Mild Cognitive Impairment: A Prospective Longitudinal Study.

Background: Biomarkers that are indicative of early biochemical aberrations are needed to predict the risk of dementia onset and progression in Alzheimer’s disease (AD). We assessed the utility of cerebrospinal fluid (CSF) neurofilament light (NfL) chain for screening preclinical AD, predicting dementia onset among cognitively healthy (CH) individuals, and the rate of cognitive decline amongst individuals with mild cognitive impairment (MCI). Methods: Neurofilament light levels were measured in CSF samples of participants (CH, n = 154 and MCI, n = 32) from the Australian Imaging, Biomarkers and Lifestyle study of ageing (AIBL). Cases of preclinical AD were identified using biomarker-guided classification (CH, amyloid-β [Aβ]+, phosphorylated-tau [P-tau]+ and total-tau [T-tau]±; A+T+/N±). The prediction of dementia onset (questionable dementia) among CH participants was assessed as the risk of conversion from Clinical Dementia Rating [CDR = 0] to CDR ≥ 0.5 over 6 years. Mixed linear models were used to assess the utility of baseline CSF NfL levels for predicting the rate of cognitive decline among participants with MCI over 4.5 years. Results: Neurofilament light levels were significantly higher in preclinical AD participants (CH, A+T+/N±) as compared to A-T-N- (p < 0.001). Baseline levels of CSF NfL were higher in CH participants who converted to CDR ≥ 0.5 over 6 years (p = 0.045) and the risk of conversion to CDR ≥ 0.5 was predicted (hazard ratio [HR] 1.60, CI 1.03–2.48, p = 0.038). CH participants with CSF NfL > cut-off were at a higher risk of developing dementia (HR 4.77, CI 1.31–17.29, p = 0.018). Participants with MCI and with higher baseline levels of CSF NfL (>median) had a higher rate of decline in cognition over 4.5 years. Conclusion: An assessment of CSF NfL levels can help to predict dementia onset among CH vulnerable individuals and cognitive decline among those with MCI.

Gait, physical function, and physical activity in three groups of home-dwelling older adults with different severity of cognitive impairment \u2013 a cross-sectional study

BackgroundThe research on associations between gait, physical function, physical activity (PA), and cognitive function is growing. Still, clinical assessments of cognitive function and motor function is often kept separate. In this study, we aimed to look at a broad range of measures of gait, physical function, and PA in three groups of home-dwelling older adults with no or questionable dementia, mild dementia, and moderate/severe dementia.MethodsThis cross-sectional study included 100 home-dwelling older adults, recruited from an outpatient geriatric memory clinic. Severity of dementia was categorised using the clinical dementia rating scale (CDR), with no or questionable dementia (CDR score 0 and 0.5), mild dementia (CDR score 1) and moderate/severe dementia (CDR score 2 and 3). We used thigh worn accelerometers to measure daily PA, the Short Physical Performance Battery (SPPB) to measure physical function, and an electronic gait mat to evaluate gait characteristics. Associations between severity of dementia and measures of PA, physical function, and gait characteristics were assessed by linear regression.ResultsParticipants’ (mean age 78.9 (SD 6.7) years, 57% women) average gait speed was 0.93 m/sec, and average upright time was 301 min/day. Statistically significant associations were found for the severity of dementia and gait speed (p=0.002), step time (p=0.001), physical function (SPPB, p=0.007), and PA (upright time, p=0.031), after adjusting for age. Overall, having no or questionable dementia was associated with faster gait speed (mean difference 0.163 (95% CI: 0.053 to 0.273)), shorter step time (-0.043 (-0.082 to -0.005)), better SPPB score (1.7 (0.5 to 2.8)), and longer upright time (78.9 (18.9 to 139.0)), compared to those with mild dementia. Furthermore, having no or questionable dementia was also associated with faster gait speed and better SPPB scores, as compared to those with moderate to severe dementia. No evidence of any differences was found between the participants with the mild dementia versus the moderate to severe dementia.ConclusionsAfter adjusting for age, we found that the no or questionable dementia group to be associated with better gait and physical function, and more PA, as compared with the two groups with mild or moderate/severe dementia. Evaluation of gait, physical function, and PA can add clinically important information of everyday functioning in memory clinics meeting geriatric patients, but investigations on how to use these results to guide interventions are still needed.

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome Scale (BPSD-DS II): Optimization and Further Validation.

Background:People with Down syndrome (DS) are at high risk to develop Alzheimer’s disease dementia (AD). Behavioral and psychological symptoms of dementia (BPSD) are common and may also serve as early signals for dementia. However, comprehensive evaluation scales for BPSD, adapted to DS, are lacking. Therefore, we previously developed the BPSD-DS scale to identify behavioral changes between the last six months and pre-existing life-long characteristic behavior.Objective:To optimize and further study the scale (discriminative ability and reliability) in a large representative DS study population.Methods:Optimization was based on item irrelevance and clinical experiences obtained in the initial study. Using the shortened and refined BPSD-DS II, informant interviews were conducted to evaluate 524 individuals with DS grouped according to dementia status: no dementia (DS, N = 292), questionable dementia (DS + Q, N = 119), and clinically diagnosed dementia (DS + AD, N = 113).Results:Comparing item change scores between groups revealed prominent changes in frequency and severity for anxious, sleep-related, irritable, restless/stereotypic, apathetic, depressive, and eating/drinking behavior. For most items, the proportion of individuals displaying an increased frequency was highest in DS + AD, intermediate in DS + Q, and lowest in DS. For various items within sections about anxious, sleep-related, irritable, apathetic, and depressive behaviors, the proportion of individuals showing an increased frequency was already substantial in DS + Q, suggesting that these changes may serve as early signals of AD in DS. Reliability data were promising.Conclusion:The optimized scale yields largely similar results as obtained with the initial version. Systematically evaluating BPSD in DS may increase understanding of changes among caregivers and (timely) adaptation of care/treatment.

People with dementia attending farm-based day care in Norway - Individual and farm characteristics associated with participants' quality of life.

Farm-based day care for people with dementia is supposed to improve the participants quality of life by using activities and resources of the farm environment to promote mental and physical health. In this paper, we describe the characteristics of those attending farm-based day care services in Norway and explore the association between individual and farm characteristics and the quality of life. A sample of 94 people with dementia who attended farm-based day care was recruited from 25 farms between January 2017 and January 2018. The data collection was performed using standardized instruments. Information about the farms was retrieved from a former study. The association between the participants' quality of life and their individual and/or farm characteristics was examined with a linear multilevel regression model. The participants had a mean age of 76years, 62% were men, and 68% had additional education after primary school. Most of them had mild (54.3%) or questionable dementia (18.3%). A few participants used antipsychotics (3.7%), tranquilizers (9.9%) and painkillers (13.6%), while a higher number used antidepressants (30.9%). Quality of life was associated with the experience of having social support (p=.023), a low score on depressive symptoms (p<.001), and spending time outdoors at the farm (p<.001). The variation between the farm-based day care services in the participants' reported quality of life was related to time spent outdoors at the farm. In light of the present study, it seems as farm-based day care is addressing people with dementia in an early stage, dominated by men, with quite good physical and medical condition. The strong association between quality of life and spending time outdoors underscores that facilitation for outdoor activity should be prioritized in all types of dementia care.

The behavioral and psychological symptoms of dementia in down syndrome (BPSD-DS) scale: comprehensive assessment of psychopathology in down syndrome

Behavioral and psychological symptoms of dementia (BPSD) have not been comprehensively studied in people with Down syndrome, despite their high risk on dementia. Anovel evaluation scale was developed to identify the nature, frequency and severity of behavioral changes (83 behavioral items in 12 clinically defined sections). Central aim was to identify items that change in relation to the dementia status. Structured interviews were conducted with informants of people with Down syndrome without dementia (DS, N = 149), with questionable dementia (DS + TD, N = 65) and with diagnosed dementia (DS + AD, N = 67). Group comparisons showed apronounced increase in frequency and severity of items about anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and, eating/drinking behavior. The proportion of individuals presenting an increase was highest in the DS + AD group and lowest in the DS group. Interestingly, among DS + TD individuals, asubstantial proportion already presented increased anxiety, sleep disturbances, apathy and depressive symptoms, suggesting that these changes may be early alarm signals of dementia. The scale may contribute to abetter understanding of the changes, adapting daily care/support, and providing suitable therapies to people with Down syndrome. The scale needs to be optimized based on the results and experiences. The applicability, reliability and validity require further study.

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) Scale: Comprehensive Assessment of Psychopathology in Down Syndrome.

People with Down syndrome (DS) are prone to develop Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. 83 behavioral items in 12 clinically defined sections were evaluated. The central aim was to identify items that change in relation to the dementia status, and thus may differentiate between diagnostic groups. Structured interviews were conducted with informants of persons with DS without dementia (DS, n = 149), with questionable dementia (DS+Q, n = 65), and with diagnosed dementia (DS+AD, n = 67). First exploratory data suggest promising interrater, test-retest, and internal consistency reliability measures. Concerning item relevance, group comparisons revealed pronounced increases in frequency and severity in items of anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and eating/drinking behavior. The proportion of individuals presenting an increase was highest in DS+AD, intermediate in DS+Q, and lowest in DS. Interestingly, among DS+Q individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy, and depressive symptoms, suggesting that these changes occur early in the course of AD. Future efforts should optimize the scale based on current results and clinical experiences, and further study applicability, reliability, and validity. Future application of the scale in daily care may aid caregivers to understand changes, and contribute to timely interventions and adaptation of caregiving.

Patients With Very Mild Dementia May Confuse Objective Cognitive Impairments With Subjective Physical Health of Quality of Life: The Tome City Project in Japan.

Many elderly people with cognitive dysfunction may observe a decrease in their health levels and quality of life (QOL). The basic concept of QOL consists of several categories including physical functions and mental health. The QOL domain that is most important for elderly people is physical health and, to a lesser extent, psychological health, social relationships, and/ or the environment. Our aim was to explore the relationships between the subjective measure of QOL, an abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) scale, and the objective measure of impairment, Clinical Dementia Rating (CDR), among elderly people in a community. Totally, 178 community dwellers aged 75 years and above agreed to participate and completed the WHOQOL-BREF; 66 (32 males, 34 females) scored a CDR of 0 (healthy), 86 (33, 53) scored a CDR of 0.5 (questionable dementia or very mild dementia), and 26 (12, 14) scored a CDR of 1 and above (dementia). According to Pearson’s correlation coefficient analysis (significance level, p < 0.05), the physical domain of the WHOQOL-BREF had significant statistical negative correlations with all CDR subscales. The CDR subscale of memory impairment had a significant statistical negative correlation with the WHOQOL-BREF subscales of the physical (r = -0.151, p = 0.044) and psychological (r = -0.232, p < 0.002) domains. The CDR subscale of home and hobbies impairment had significant statistical negative correlations with all WHOQOL-BREF subscales including the physical (r = -0.226, p = 0.002), psychological (r = -0.226, p = 0.002), social (r = -0.167, p = 0.026), and environmental (r = -0.204, p = 0.006) domains. Patients with very mild dementia may confuse cognitive impairment and physical disabilities. In the future, we need to systematically combine memory clinics and all departments related to the elderly for the successful early detection and rehabilitation of, and long-term care for, dementia.

Antipsychotic prescription and mortality in hospitalized older persons.

Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients. We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale. Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5-9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality. We found that the prescription of antipsychotic drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short-term antipsychotic prescriptions (for acutely ill patients) may have a different effect than long-term, repeated prescriptions.

The relationship among unawareness of memory impairment, depression, and dementia in older adults with memory impairment in Singapore.

Previous research has studied the relationships among unawareness of memory impairment, depression, and dementia in older adults with severe dementia, but it has not considered the associations and clinical implications at earlier stages of memory impairment. This study therefore sought to examine the relationship among unawareness of memory impairment, depression, and dementia in older adults with memory impairment in Singapore. The participants were 751 older adults with memory impairment in Singapore. They were assessed for objective and subjective memory loss, depression, and dementia severity. Participants' subjective memory loss was determined based on a self-appraisal question on memory, and their objective memory loss was calculated based on their performance on three cognitive tasks. Unawareness was assessed based on the contrast between subjective and objective memory loss. Descriptive statistics revealed a high prevalence of unawareness (80.4%). Logistic regression analysis revealed that gender and marital status were significantly associated with unawareness. Men (odds ratio (OR) = 2.5) and those who were divorced or separated (OR = 23.0) were more likely to be unaware than women and those who were married, respectively. After chronic conditions and demographic characteristics were controlled for, multivariate logistic regression analyses revealed that older adults with depression were less likely (OR = 0.2) to be unaware than those without depression. Unawareness was also related with dementia severity; older adults with questionable (OR = 0.3) and mild dementia (OR = 0.4) were less likely to be unaware than someone without dementia. Unawareness of memory impairment was common among older adults with memory impairment. However, unawareness may be the result of denial as a strategy for coping with memory loss of which the older adult is aware. Psychological care should be integrated into the overall treatment management of dementia to mitigate the possible risk of depression while increasing individual awareness of memory loss.

A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12.

Older diabetic people are at risk of cognitive decline. Vitamin B12 deficiency in older people is associated with cognitive impairment and Alzheimer's disease. Vitamin B12 deficiency may therefore contribute to cognitive decline in older diabetic people. We therefore performed a randomized placebo-controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with mild vitamin B12 deficiency. 271 diabetic non-demented outpatients aged 70 years or older with plasma vitamin B12 150-300pmol/L in outpatient clinics were randomly assigned to take either methylcobalamin 1000μg or two similar looking placebo tablets once daily for 27 months. All subjects were followed up at 9 monthly intervals. The primary outcome is cognitive decline as defined by an increase in clinical dementia rating scale (CDR) global score. The secondary outcomes included Neuropsychological Test Battery (NTB) z-scores, serum methymalonic acid (MMA) and homocysteine. The subjects in the trial groups were well matched in clinical characteristics, except that active intervention group had more smokers. 46.5% and 74.1% had elevated serum methymalonic acid (≥0.21μmol/L) and homocysteine (≥13μmol/L) respectively. 44% of the subjects had CDR score of 0.5 suggesting questionable dementia. At month 9 and 27, serum MMA and homocysteine was significantly reduced in the active treatment group, when compared with placebo group. (P<0.0001, student t test) At month 27, there was no significant group difference in changes in CDR or NTB z-scores. Exclusion of smokers did not alter the results. Subgroup analysis of high MMSE and serum MMA showed similar results. Vitamin B12 supplementation did not prevent cognitive decline in older diabetic patients with borderline vitamin B12 status. ClinicalTrials.gov: NCT02457507.

THYROID HORMONES, COGNITIVE IMPAIRMENT, DEPRESSION AND SUBJECTIVE MEMORY COMPLAINT IN COMMUNITY-DWELLING ELDERS

It was the aim to examine the association of the thyroid-related hormones with cognitive function, depression, and subjective memory impairment in community-dwelling elders with questionable dementia. The sample consisted of 399 community residents with ‘questionable dementia’ aged 60 or over in whom serum thyroid-related hormones [thyroid stimulating hormone (TSH) and thyroxine] had been assayed. Cognitive impairment was defined using the Korean version of the Consortium Establish a Registry for Alzheimer’s Disease. Depression was diagnosed using the Korean version of Geriatric Depression Scale and subjective memory complaint (SMC) was checked using the subjective memory complaints questionnaire (SMCQ). Age, gender, education, and the presence of apolipoprotein E ε4 were included as covariates. There was a significant positive association between verbal fluency test (VFT) score and serum TSH levels (p = 0.01). There was a significant negative association between SMCQ total score and word list memory test (WLMT)(p = 0.002) or word list recall test (WLRT) score (p = 0.013). Lower serum TSH levels were associated with semantic memory (VFT), and we found that SMC was associated with episodic memory (WLMT and WLRT) in this sample.

Prevalence and prognosis of prodromal Alzheimer's disease as assessed by magnetic resonance imaging and 18F-fluorodeoxyglucose-positron emission tomography in a community: reanalysis from the Osaki-Tajiri Project.

Dubois et al. proposed the criteria for prodromal Alzheimer's disease (AD) to detect dementia in its very early stage. Because detection requires magnetic resonance imaging and (18) F-fluorodeoxyglucose-positron emission tomography (PET), the prevalence and prognosis have not been fully investigated. Our database included 346 healthy participants (Clinical Dementia Rating (CDR) 0), 119 with questionable dementia (CDR 0.5), and 32 dementia participants (CDR 1+) and was applied to investigate the prevalence of prodromal AD. Forty-four CDR 0.5 participants (37%) were randomly selected to undergo (18) F-fluorodeoxyglucose-PET. The same percentage was applied to select 128 CDR 0 and 12 CDR 1 + participants (total: n = 184) to calculate the prevalence. A neuroradiologist classified the PET images in a blinded manner based on the criteria of Silverman et al. Participants were considered to have prodromal AD if they exhibited 'parietal/temporal +/- frontal hypometabolism' (PET) with hippocampal atrophy (magnetic resonance imaging). Eighteen CDR 0.5 participants (40.9%) met the criteria for prodromal AD, which was a prevalence rate of 9.8% among older adults aged ≥ 65 years. Thirteen prodromal AD participants (72%) converted to AD during the 5-year follow-up period. The concept and criteria for prodromal AD are useful for predicting which subjects in a community will convert to AD.

Optimal likelihood-ratio multiple testing with application to Alzheimer’s disease and questionable dementia

BackgroundControlling the false discovery rate is important when testing multiple hypotheses. To enhance the detection capability of a false discovery rate control test, we applied the likelihood ratio-based multiple testing method in neuroimage data and compared the performance with the existing methods.MethodsWe analysed the performance of the likelihood ratio-based false discovery rate method using simulation data generated under independent assumption, and positron emission tomography data of Alzheimer’s disease and questionable dementia. We investigated how well the method detects extensive hypometabolic regions and compared the results to those of the conventional Benjamini Hochberg-false discovery rate method.ResultsOur findings show that the likelihood ratio-based false discovery rate method can control the false discovery rate, giving the smallest false non-discovery rate (for a one-sided test) or the smallest expected number of false assignments (for a two-sided test). Even though we assumed independence among voxels, the likelihood ratio-based false discovery rate method detected more extensive hypometabolic regions in 22 patients with Alzheimer’s disease, as compared to the 44 normal controls, than did the Benjamini Hochberg-false discovery rate method. The contingency and distribution patterns were consistent with those of previous studies. In 24 questionable dementia patients, the proposed likelihood ratio-based false discovery rate method was able to detect hypometabolism in the medial temporal region.ConclusionsThis study showed that the proposed likelihood ratio-based false discovery rate method efficiently identifies extensive hypometabolic regions owing to its increased detection capability and ability to control the false discovery rate.

芳香を用いた認知症のスクリーニング方法

The medical inspection which detects the early stage dementia is difficult because elderly person have a negative impression o the inspection. For this reason, the purpose of this study is to propose a screening method which can detect the dementia by using the simple olfactory identification test. Authors focused on the decrease of the olfactory function. Before the investigation, authors selected the seven odors which can be easily identified and which has not uncomfortable impression. These seven odors were selected among twelve odors that are included in OSIT-J (Odor Identification Test for Japanese). Experimental participants were eight healthy elderly people and twenty elderly people with dementia living at the nursing home. As a result, we clarified that olfactory function of elderly people with dementia is significantly lower(p < 0.003）than healthy elderly people. Furthermore, ROC （Receiver Operating Characteristic）analysis demonstrated that the investigation using seven odors has high screening capacity (AUC：Area Under the Curve = 0.95). Through these investigations results, we devised a screening method which has an accuracy of 75 percent for screening. The devised method may detect elderly people with questionable dementia more accurately by increasing the number of experimental participants.

Apolipoprotein E Gene Variants of Alzheimer&amp;apos;s Disease and Vascular Dementia Patients in a Community Population of Nanking

To explore apolipoprotein E gene variants distribution among the patients of Alzheimer's disease and vascular dementia for the elderly community population in Nanking, the polymerase chain reaction and restriction fragment length polymorphism techniques were employed to analyze the gene frequency of apolipoprotein E (ApoE) for 113 cases with Alzheimer's disease (AD), 85 cases with vascular dementia (VaD), 147 cases with questionable dementia (QD), and 396 dementia-free controls. It was found that ApoE ε4 gene container (37.17%) and allele frequency (21.24 ± 2.72) of ApoE ε4 in AD group were significantly higher than those in both control and VaD group (p < 0.05). With the increment of ε4 gene dose, the incidence of the AD was significantly increased. Compared with the control group, ApoE ε4 had risk ratio (RR) of 1.82 to develop AD (p = 4e-4), and attributable risk percentage (ARP) of 45%. These results suggest that ApoE ε4 gene may be responsible for up to 45% of the genetic component of Alzheimer's disease, and may act as a discriminator between AD and VaD as well.

Diagnostic Utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: Major and Mild Neurocognitive Disorders

ObjectivesThe Montreal Cognitive Assessment (MOCA) is a screening tool for mild cognitive impairment (MCI) and dementia. The new criteria for Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM-5) mild neurocognitive disorder (NCD) define participants with cognitive decline but no dementia, and major NCD (dementia). We explored the usefulness of MOCA to detect major and mild NCD. DesignCross-sectional test research. SettingTertiary hospital memory clinic and community-based Singapore Longitudinal Aging Study (SLAS). ParticipantsParticipants with questionable dementia (clinical dementia rating, CDR = 0.5) and early dementia (CDR ≤1) over a period of 1 year were identified from the memory clinic registry. The patient records were reviewed and the diagnostic labels of major and mild NCD were applied accordingly. Healthy controls (HC) (CDR = 0, Mini-Mental State Examination >26) were recruited from the on-going SLAS. MeasurementsMajor and mild NCD were diagnosed based on medical history, clinical examination, basic and instrumental activities of daily living, locally validated bedside cognitive tests (Mini-Mental State Examination, Frontal Assessment Battery, and Clock Drawing Test), relevant laboratory investigations and standardized neuropsychological assessment. ResultsTwo hundred fifty-one participants were included (41 mild NCD, 64 major NCD, 146 HC). On receiver operating characteristic curve analysis, the diagnostic performance by area under the curve (AUC) for MOCA was 0.99 [95% confidence interval (CI) 0.98–1.0] for major NCD and 0.77 (95% CI 0.67–0.86) for mild NCD. For diagnosis of mild NCD, MOCA performed better in those with lower education (primary and below) (AUC 0.90) compared with those with secondary education and beyond (AUC 0.66). ConclusionMOCA has high diagnostic utility for major NCD but its usefulness in detecting mild NCD is more modest. Possible reasons include greater heterogeneity in participants with mild NCD and how “quantified clinical assessment” in the DSM-5 mild NCD criteria is interpreted and operationalized.

Prevalence of dementia and factors associated with dementia in rural Bangladesh: data from a cross-sectional, population-based study.

There are currently no published reports of dementia prevalence or factors associated with dementia occurrence in Bangladesh. The aims are to report the prevalence of definite and questionable dementia in rural Bangladesh, and examine factors potentially associated with dementia occurrence, including sociodemographic, clinical, social, and nutritional factors. We used data from a population-based, cross-sectional study from Matlab, in rural Bangladesh, on 471 persons aged 60+ years. Participants underwent a clinical examination including diagnosis of somatic disorders, and a structured interview including questions about sociodemographic and social factors. Nutritional status was measured with the Mini Nutritional Assessment, and blood tests were conducted to assess a range of nutritional and clinical aspects. Age- and sex-specific dementia prevalence was calculated. Crude and adjusted logistic regression was used to examine associations between dementia and clinical, social, and nutritional factors. Dementia was diagnosed using a two-step procedure by physicians according to DSM-IV criteria. The prevalence of questionable dementia was 11.5% and definite dementia was 3.6%. Dementia prevalence increased with increasing years of age (adjusted OR: 1.04; 95% CI = 1.002-1.1) and decreased with more years of education (adjusted OR: 0.8; 95% CI = 0.6-0.99). Being malnourished increased the odds of dementia almost six-fold (adjusted OR: 5.9; 95% CI = 1.3-26.3), while frequent participation in social activities was associated with a decreased odds (adjusted OR: 0.5; 95% CI = 0.2-0.9). The prevalence of dementia in rural Bangladesh is similar to other countries in the South Asia region, but lower than reports from other world regions. Malnutrition is strongly associated with dementia occurrence, and is a relevant area for future research within low-income countries.