Exploring the prevalence of undetected bradyarrhythmia in dementia with Lewy bodies.

PURPOSE: To explore the prevalence of undetected bradyarrhythmia in a cohort of people with dementia with Lewy bodies. METHODS: Thirty participants diagnosed with dementia with Lewy bodies were enrolled from three memory clinics in southern Sweden between May 2021 and November 2022. None had a history of high-grade atrioventricular block or sick sinus syndrome. Each participant underwent orthostatic testing, cardiac [123I]metaiodobenzylguanidine scintigraphy and 24-h ambulatory electrocardiographic monitoring. Concluding bradyarrhythmia diagnosis was obtained until the end of December 2022. RESULTS: Thirteen participants (46.4%) had bradycardia at rest during orthostatic testing and four had an average heart rate < 60 beats per minute during ambulatory electrocardiographic monitoring. Three participants (10.7%) received a diagnosis of sick sinus syndrome, of whom two received pacemaker implants to manage associated symptoms. None received a diagnosis of second- or third-degree atrioventricular block. CONCLUSION: This report showed a high prevalence of sick sinus syndrome in a clinical cohort of people with dementia with Lewy bodies. Further research on the causes and consequences of sick sinus syndrome in dementia with Lewy bodies is thus warranted.

Development of the Swedish anticholinergic burden scale (Swe-ABS).

BACKGROUND: Drugs with anticholinergic properties are associated with cognitive adverse effects, especially in patients vulnerable to central muscarinic antagonism. A variety of drugs show weak, moderate or strong anticholinergic effects. Therefore, the cumulative anticholinergic burden should be considered in patients with cognitive impairment. This study aimed to develop a Swedish Anticholinergic Burden Scale (Swe-ABS) to be used in health care and research. METHODS: A systematic literature review was conducted in PubMed and Ovid Embase to identify previously published tools quantifying anticholinergic drug burden (i.e., exposure). Drugs and grading scores (0-3, no to high anticholinergic activity) were extracted from identified lists. Enteral and parenteral drugs authorized in Sweden were included. Drugs with conflicting scores in the existing lists were assessed by an expert group. Two drugs that were not previously assessed were also added to the evaluation process. RESULTS: The systematic literature search identified the following nine anticholinergic burden scales: Anticholinergic Activity Scale, Anticholinergic Burden Classification, updated Anticholinergic Cognitive Burden scale, Anticholinergic Drug Scale, Anticholinergic Load Scale, Anticholinergic Risk Scale, updated Clinician-rated Anticholinergic Scale, German Anticholinergic Burden Scale and Korean Anticholinergic Burden Scale. A list of drugs with significant anticholinergic effects provided by The Swedish National Board of Health and Welfare was included in the process. The suggested Swe-ABS consists of 104 drugs scored as having weak, moderate or strong anticholinergic effects. Two hundred and fifty-six drugs were listed as having no anticholinergic effects based on evaluation in previous scales. In total, 62 drugs were assessed by the expert group. CONCLUSIONS: Swe-ABS is a simplified method to quantify the anticholinergic burden and is easy to use in clinical practice. Publication of this scale might make clinicians more aware of drugs with anticholinergic properties and patients' total anticholinergic burden. Further research is needed to validate the Swe-ABS and evaluate anticholinergic exposure versus clinically significant outcomes.

Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

Choral Singing Enriches Everyday Life for People With Mild to Moderate Dementia and Their Family Caregivers.

Dementia causes substantial suffering for affected persons and their family caregivers. Because no cure is available, it is important to investigate how alternative therapies can improve life for these individuals. For the current study, persons with dementia (PwD) were recruited from a specialized Memory Clinic in Sweden to engage in a choral singing intervention for 1 hour per week for four semesters. PwD were encouraged to bring a family caregiver to the sessions; both were interviewed and data were analyzed using qualitative content analysis. The choral singing intervention appeared to become an important social context for PwD and family caregivers and had a positive impact on relationship, mental well-being, mood, and memory. The intervention appeared to act as an enriched environment for all participants. Choral singing interventions for PwD and their family caregivers is a simple means to create a social context and improve general well-being. [Journal of Psychosocial Nursing and Mental Health Services, 60(5), 29-36.].

"I Know Hyena. Do you Know Hyena?" Challenges in Interpreter-Mediated Dementia Assessment, Focusing on the Role of the Interpreter.

Dementia assessment requires functional communication and interaction between healthcare professionals and the patient being assessed. These can be affected by the requirement for an interpreter to communicate with the patient. The purpose of this study was to elucidate the interactions between patient, healthcare professionals and interpreter, focusing on the role of the interpreter and the challenges that may arise in interpreter-mediated dementia assessment. The study had an ethnographic design in which the data consisted of audio and video recordings of 19 dementia assessments conducted in the presence of an interpreter. The data were analyzed using the constant comparative method. The results showed that the interpreter could affect the patient's performance and results during the dementia assessment. The interpreter could alter the meaning and content of what was communicated, sometimes change information and instructions exchanged between the patient and healthcare professionals, could avoid interpreting everything being said, and occasionally made their own corrections to what was being communicated. This occurred mainly because of the interpreter's lack of linguistic skills and the interpreter failing to adhere to the ethical guidelines governing their profession. These challenges could also occur when the interpreter was not familiar with the context of dementia assessment. Alterations made by the interpreter to what was being communicated could lead to incorrect evaluation of the patient's cognitive abilities and health status. This, in turn, may lead to misjudgment of the patient's remaining resources and symptoms and their required treatment and support.

Plasma Phospho-Tau Identifies Alzheimer's Co-Pathology in Patients with Lewy Body Disease.

BACKGROUND: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives. OBJECTIVE: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia. METHODS: In this cross-sectional study we investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau-PET imaging (18 F-RO948). RESULTS: Plasma phospho-tau217 correlated with plasma phospho-tau181, CSF phospho-tau217 (rs = 0.68, P < 0.001), and negatively with CSF ß-amyloid42/40 (rs = -0.52, P = 0.001). Plasma phospho-tau217 and phospho-tau181 correlated with tau-PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau-PET status and ß-amyloid status (area under the curve > 0.78 and > 0.81, respectively). CONCLUSION: Plasma phospho-tau might be a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment.

OBJECTIVES: Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). METHODS: Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n = 111) and after (n = 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. RESULTS: We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p < 0.001), WMC from 69 to 86% (p < 0.01), and GCA from 54 to 82% (p < 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p < 0.001). There was a significant increase in TPR from 10 to 55% for MTA. CONCLUSION: This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse. KEY POINTS: • Introducing visual rating scales in clinical practice increases the reporting frequency of MTA, WMC, and GCA in the diagnostic work up of subjective and mild cognitive impairment. • Introducing visual rating scales has an effect on the true positive rate of reported MTA. • Compliance with contextual radiology templates remains low when use of the template is not enforced by the department leadership.

Heritability and genetic variance of dementia with Lewy bodies.

Recent large-scale genetic studies have allowed for the first glimpse of the effects of common genetic variability in dementia with Lewy bodies (DLB), identifying risk variants with appreciable effect sizes. However, it is currently well established that a substantial portion of the genetic heritable component of complex traits is not captured by genome-wide significant SNPs. To overcome this issue, we have estimated the proportion of phenotypic variance explained by genetic variability (SNP heritability) in DLB using a method that is unbiased by allele frequency or linkage disequilibrium properties of the underlying variants. This shows that the heritability of DLB is nearly twice as high as previous estimates based on common variants only (31% vs 59.9%). We also determine the amount of phenotypic variance in DLB that can be explained by recent polygenic risk scores from either Parkinson's disease (PD) or Alzheimer's disease (AD), and show that, despite being highly significant, they explain a low amount of variance. Additionally, to identify pleiotropic events that might improve our understanding of the disease, we performed genetic correlation analyses of DLB with over 200 diseases and biomedically relevant traits. Our data shows that DLB has a positive correlation with education phenotypes, which is opposite to what occurs in AD. Overall, our data suggests that novel genetic risk factors for DLB should be identified by larger GWAS and these are likely to be independent from known AD and PD risk variants.

Structural imaging findings on non-enhanced computed tomography are severely underreported in the primary care diagnostic work-up of subjective cognitive decline.

PURPOSE: The purpose of this study was to investigate how structural imaging findings of medial temporal lobe atrophy (MTA), posterior cortical atrophy (PCA), global cortical atrophy (GCA), white matter changes (WMC), and Evans' index/width of lateral ventricles (EI/WLV) are reported in the primary care diagnostic work-up of patients with subjective cognitive decline or mild cognitive impairment. METHODS: We included 197 patients referred to a non-enhanced computed tomography (NECT) as part of the diagnostic work-up. We compared the frequencies of reported findings in radiology reports written by neuroradiologists and general radiologists with actual pathological findings in a second view done by a single neuroradiologist using the MTA, PCA, GCA, WMC, and EI/WLV visual rating scales. Structural findings were also compared to cognitive tests. RESULTS: We found that MTA and PCA were clearly underreported by both neuroradiologists and general radiologists. The presence of GCA and WMC was also underreported among general radiologists. Only MTA showed a clear association with cognitive test results. CONCLUSIONS: We believe that the use of visual rating scales should be put into clinical practice to increase the yield of clinical NECT exams in the investigation of cognitive impairment. Special emphasis should be put on reporting MTA.

Psychotropic and anti-dementia treatment in elderly persons with clinical signs of dementia with Lewy bodies: a cross-sectional study in 40 nursing homes in Sweden.

BACKGROUND: Elderly persons with a dementia diagnosis often suffer from different neuropsychiatric symptoms (NPS) such as delusions, hallucinations, depression, anxiety, irritability and agitation. Currently, the medical treatment for NPS consists mostly of psychotropic medication such as hypnotics/sedatives, anxiolytics and antipsychotics. In elderly persons with dementia, usage of antipsychotics is less appropriate because of the risk of side effects such as parkinsonism, rapid cognitive decline, cerebrovascular events and finally mortality. Furthermore, elderly persons with dementia with Lewy bodies (DLB) are often hypersensitive to antipsychotics with numerous serious adverse events such as somnolence, sedation, extra-pyramidal symptoms, delirium and increased mortality. The aim of this study was to investigate the usage of psychotropics with a focus on antipsychotics and anti-dementia medication (according to the Anatomical Therapeutic Chemical Classification System) in elderly persons with clinical signs of DLB living in dementia nursing homes (NHs) in Sweden. METHODS: Between 2012 and 2013, we applied a specially designed questionnaire that covered the clinical DLB features according to the consensus criteria of DLB. We also collected computerized medical lists from the Swedish National Medication Dispensing System from the same period. All dementia NHs (n = 40) in Malmö, the third largest city in Sweden, were covered. Of 650 eligible residents, 610 (94%) were included with 576 medical lists. The mean age was 86 years and 76% were women. RESULTS: Treatment with antipsychotics was seen in 22% of residents, hypnotics/sedatives in 41%, antidepressants in 50% and anxiolytics in 58%. We also found an increasing usage of antipsychotics from 25% to 43% in residents with the increasing number of DLB features. Anti-dementia medications were found in 45% of the elderly with a dementia diagnosis. However, residents with two or more DLB features had less anti-dementia medication (37%) than the rest of the dementia-diagnosed NH residents (62-69%). CONCLUSIONS: Residents with 2-4 DLB clinical features in Swedish NHs receive an unfavourable medical treatment with high antipsychotic usage and insufficient anti-dementia medication. These findings show the importance of identifying elderly persons with DLB features more effectively and improving the collaboration with nursing care to provide better medical prescription.

Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.

Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.

Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia.

INTRODUCTION: Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. METHODS: From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. RESULTS: The Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. CONCLUSIONS: Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. © 2016 International Parkinson and Movement Disorder Society.

Cholinesterase inhibitors do not alter the length of stay in nursing homes among patients with Alzheimer's disease: a prospective, observational study of factors affecting survival time from admission to death.

BACKGROUND: The survival time in nursing homes (NHs) in Alzheimer's disease (AD) might be affected by sociodemographic/clinical characteristics, rate of disease progression, and use of specific medications and community-based services. Whether different aspects of cholinesterase inhibitor (ChEI) therapy modify time spent in NHs is unclear. Therefore, we examined the relationship between these potential predictors and survival time in NHs. METHODS: This prospective, multicenter study of ChEI treatment in clinical practice included 220 deceased patients clinically diagnosed with mild-to-moderate AD who were admitted to NHs during the study. Cognitive and activities of daily living (ADL) performance, ChEI dose, and amount of services used/week were evaluated every 6 months over 3 years. Dates of nursing-home placement (NHP) and death were recorded. Variables that determined survival time in NHs were analyzed using general linear models. RESULTS: The mean survival time in NHs was 4.06 years (men, 2.78 years; women, 4.53 years; P < 0.001). The multivariate model showed that a shorter stay in NHs was associated with the interaction term male living with a family member, use of antihypertensive/cardiac therapy or anxiolytics/sedatives/hypnotics, and worse basic ADL at NHP, but not with age or cognitive and instrumental ADL capacities. CONCLUSIONS: Increased community-based care did not reduce the survival time in NHs among individuals with AD. Men living with family spent significantly less time in NHs compared with the corresponding women, which suggests that the situation of female spouses of AD patients may need attention and possibly support. There was no indication that different aspects of ChEI therapy, e.g., drug type, dose, or duration, alter survival time in NHs.

Reliability, validity and clinical correlates of the Quality of Life in Alzheimer's disease (QoL-AD) scale in medical inpatients.

BACKGROUND: There is a lack of standardisation in quality of life (QoL) measurements to be used in older multimorbid patients. An ideal QoL measurement should be reliable, valid, subjective, multidimensional, feasible and generic. We hypothesised that the QoL-AD (Quality of Life in Alzheimer's Disease) scale could have these properties. Our aim was to determine the psychometric properties and clinical correlations of QoL-AD in a population of elderly, multimorbid medical inpatients. METHODS: QoL-AD was performed in 200 medical inpatients, and available caregivers. Reliability was determined using cronbach's alpha and corrected item-total correlations. The agreement between patient and proxy ratings were examined using intra-class correlations (ICC). Correlations between QoL-AD and demographic data, comorbidity, cognitive tests, ADL (activities of daily living) and depression were examined. To characterise the underlying constructs of QoL-AD, an exploratory factor analysis was performed. RESULTS: In total, 199 patients fulfilled the QoL-AD rating, with 139 proxy ratings. Cronbach's alpha (95 % CI) was 0.74 (0.68-0.79) for patients and 0.86 (0.83-0.90) for proxies. Patient-proxy ICC (95 % CI) was 0.31 (0.16-0.46). Lower QoL was correlated to depression, cognitive impairment, ADL impairment and solitary living, but not with comorbidity. The factor analysis gave a three-factor solution, with factors representing phsyical, social and psychological well-being. CONCLUSION: The QoL-AD scale showed some promising properties but more research is needed before it can be recommended in this setting. If replicated, the finding that cognitive impairment, depression and ADL impairment were more associated with lower QoL than somatic comorbidity could have clinical implications for further studies aiming to improve QoL in this population.

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services.

BACKGROUND/AIMS: Factors including rate of disease progression, different aspects of cholinesterase inhibitor (ChEI) treatment, and use of community-based services might affect the longitudinal outcome of Alzheimer's disease (AD). Whether these factors alter life expectancy in AD is unclear. We therefore examined the association between long-term ChEI therapy and survival. METHODS: The present study included 1,021 patients with a clinical diagnosis of AD and a Mini-Mental State Examination score of 10-26 at baseline from a 3-year, prospective, multicenter study of ChEI therapy in clinical practice. The relationship of potential predictors with mortality was analyzed using Cox regression models. RESULTS: After up to 16 years of follow-up, 841 (82%) of the participants had died. In the Alzheimer's Disease Assessment Scale-cognitive subscale, a mean decline of ≥ 4 points/year or ≥ 2 points/year on the Physical Self-Maintenance Scale was a risk factor for an earlier death. In the multivariate models, longer survival was associated with higher ChEI dose and longer duration of treatment. Users of community-based services at baseline exhibited a 1-year shorter mean life expectancy than nonusers. CONCLUSION: A longer survival time can be anticipated for AD patients with slower deterioration who receive and tolerate higher ChEI doses and a longer duration of treatment.

Memantine improves attention and episodic memory in Parkinson's disease dementia and dementia with Lewy bodies.

OBJECTIVE: In both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), attentional dysfunction is a core clinical feature together with disrupted episodic memory. This study evaluated the cognitive effects of memantine in DLB and PDD using automated tests of attention and episodic memory. METHODS: A randomised double-blind, placebo-controlled, 24-week three centre trial of memantine (20 mg/day) was conducted in which tests of attention (simple and choice reaction time) and word recognition (immediate and delayed) from the CDR System were administered prior to dosing and again at 12 and 24 weeks. Although other results from this study have been published, the data from the CDR System tests were not included and are presented here for the first time. RESULTS: Data were available for 51 patients (21 DLB and 30 PDD). In both populations, memantine produced statistically significant medium to large effect sized improvements to choice reaction time, immediate and delayed word recognition. CONCLUSIONS: These are the first substantial improvements on cognitive tests of attention and episodic recognition memory identified with memantine in either DLB or PDD.

Medial temporal lobe atrophy is underreported and may have important clinical correlates in medical inpatients.

BACKGROUND: The diagnostic workup in dementia includes brain imaging with reading focussed on signs of cerebrovascular and neurodegenerative disease. We hypothesised that these findings may be underreported in hospital patients, where imaging is often performed to rule out obvious pathology such as haemorrhage. In this study, we review cranial computed tomography (CT) in medical inpatients for white matter changes and atrophy. Our aim was to determine the clinical relevance of such findings and to what extent they were underreported. METHODS: Records from 200 inpatients aged over 60 years, who had been subjected to MMSE (mini-mental state examination) and CDT (clock-drawing test), were reviewed for cranial CT. Transverse and coronal slices were reassessed using visual rating scales regarding white matter changes (WMC), global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA). Findings were compared with the original radiology reports and cognitive test results. RESULTS: Cranial CT had been performed in 94 of 200(47 %) patients. Of these, 58(62 %) had abnormal WMC, 35(37 %) abnormal GCA and 34(36 %) abnormal MTA. All three findings had associations with cognitive test results. Abnormal MTA was associated with lower results on the overall score on MMSE and on orientation, memory and language items. All three measurements were underreported in the original radiology reports; none of the 34 patients with abnormal MTA had been reported originally. CONCLUSIONS: Signs of neurodegenerative disease, especially MTA, were highly underreported in cranial CT scans performed in medical inpatients. At the same time, MTA seemed to hold the most important clinical correlates. Our results suggest that MTA should be reported more regularly in this setting.

Determining the association of the 5HTTLPR polymorphism with delusions and hallucinations in Lewy body dementias.

OBJECTIVES: To determine whether the 5HTTLPR serotonin transporter polymorphism is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). DESIGN: Prospective cohort study. PARTICIPANTS: A total of 187 individuals, recruited from centres in Norway, Sweden, and the United Kingdom were included in this study; 97 with clinically or neuropathologically diagnosed DLB/PDD and 90 cognitively normal individuals as a comparison group. MEASUREMENTS: All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer disease, the Neuropsychiatric Inventory, or the Present Behavioural Examination. Severity of cognitive impairment was measured using the Mini Mental State Examination (MMSE). Individuals were genotyped for the 5HTTLPR polymorphism. RESULTS: Logistic regression demonstrated that homozygosity for the L/L genotype and lower MMSE were associated with an increased risk for delusions (odds ratio: 11.5 and 1.16, respectively). Neither was significantly associated with hallucinations. CONCLUSIONS: This study is the first to demonstrate the 5HTTLPR polymorphism is associated with delusions in Lewy body dementias, with important implications regarding the mechanisms underlying this symptom across the AD/DLB/PDD spectrum. Further studies are warranted to investigate this relationship further and examine treatment opportunities.

Risk factors that affect life expectancy in Alzheimer's disease: a 15-year follow-up.

BACKGROUNDS/AIMS: Future disease-modifying therapies might affect the expected life span in Alzheimer's disease (AD). Our aim was to identify factors that influence life expectancy in cholinesterase inhibitor (ChEI)-treated patients. METHODS: This study included 791 deceased individuals with a clinical diagnosis of AD and a Mini-Mental State Examination score of 10-26 at baseline who were recruited from a 3-year, prospective, multicenter study of ChEI therapy in clinical practice. The participants' date of death was recorded and their survival was compared with the gender- and age-matched general population. RESULTS: The mean survival time after the start of ChEI therapy (time of AD diagnosis) was 5.10 years for men and 6.12 years for women. Better cognitive ability, less impaired basic functional capacity, and fewer medications, but not education level or apolipoprotein E (APOE) genotype, were independent prognostic factors of longer survival after diagnosis, after controlling for gender and age. CONCLUSION: AD shortens life expectancy in ChEI-treated patients diagnosed before the age of 85 years, similar to that reported previously for untreated individuals. A longer life span was observed in the eldest patients (≥85 years) compared with untreated cohorts, which did not differ from that observed in the general population. Higher education or carrying two APOE ε4 alleles were risk factors for earlier death.

Response to cholinesterase inhibitors affects lifespan in Alzheimer's disease.

BACKGROUND: A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer's disease (AD). Whether the individual-specific response, specific ChEI agent or dose affects mortality is unclear. We aimed to examine the relationship between the 6-month response to ChEI and lifespan. METHODS: Six hundred and eighty-one deceased patients with a clinical AD diagnosis and a Mini-Mental State Examination (MMSE) score of 10-26 at the start of ChEI therapy (baseline) were included in a prospective, observational, multicentre study in clinical practice. At baseline and after 6 months of treatment, the participants were assessed using the MMSE, the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician's Interview-Based Impression of Change (CIBIC), the Instrumental Activities of Daily Living (IADL) scale, and the Physical Self-Maintenance Scale (PSMS). The individuals' socio-demographic characteristics, ChEI dose, and date of death were recorded. Responses to ChEI and the association of possible risk factors with survival were analysed using general linear models. RESULTS: A longer lifespan (mean of 0.5 years) was observed among the improved/unchanged patients, as measured by MMSE or CIBIC score, but not by ADAS-cog score, after 6 months of ChEI therapy. In the multivariate models, increased survival time was independently related to a better 6-month response in MMSE, CIBIC, IADL, and PSMS scores, female sex, no antihypertensive/cardiac or antidiabetic therapy, younger age, lower education, milder disease stage at baseline, and higher ChEI dose. Apolipoprotein E genotype did not affect mortality significantly. The patients who received a higher ChEI dose during the first 6 months had a mean lifespan after baseline that was 15 months longer than that of those who received a lower dose. CONCLUSIONS: A better short-term response to ChEI might prolong survival in naturalistic AD patients. In individuals who received and tolerated higher ChEI doses, a longer lifespan can be expected.