Measures Of Dementia Severity Research Articles

Neuropsychological assessment of financial skills in mild cognitive impairment, Alzheimer’s disease and frontotemporal dementia

AbstractBackgroundThe capacity to handle money and personal finances is crucial for living independently. Cognitive decline can lead to financial mismanagement (e.g., forgetting to pay bills, overspending) and exploitation (e.g., falling for financial scams). While greater susceptibility to financial mismanagement and exploitation is commonly reported by carers of people with dementia, objective neuropsychological measures of these financial skills are scarce. It is also unclear whether profiles of change in financial skills vary across different stages and subtypes of dementia.MethodA normative sample of 112 healthy controls and individuals with mild cognitive impairment (MCI; n = 16), Alzheimer’s disease (AD; n = 7) or behavioural‐variant frontotemporal dementia (bvFTD; n = 18) completed a novel neuropsychological Test of Financial Skills (TOFS), which assessed performance across three key areas: everyday financial tasks, susceptibility to financial scams and financial goal planning. For all patients and controls, measures of dementia severity (Clinical Dementia Rating Scale) and general cognition (Addenbrooke’s Cognitive Examination, 3rd Ed.) were also collected.ResultRelative to controls, AD and bvFTD patients showed lower overall performance on the TOFS, whereas MCI patients did not differ significantly from controls. While AD and bvFTD patients showed similar levels of impairment on everyday financial tasks and financial goal planning, bvFTD patients performed significantly worse on the financial scams subtest. Across all participants, lower TOFS performance was associated with greater dementia severity and cognitive impairment.ConclusionOur results are consistent with previous studies of carer‐reported changes in financial mismanagement and exploitation in people with dementia. Notably, we found important differences in the areas of financial skills impacted by different stages and subtypes of dementia. These findings provide novel insights into the different factors that contribute to deficits in financial skills in people with dementia, highlight the importance of objective neuropsychological assessments in this area, and open avenues for targeted financial support strategies.

Claims-Based Frailty Index as a Measure of Dementia Severity in Medicare Claims Data.

Dementia severity is unavailable in administrative claims data. We examined whether a claims-based frailty index (CFI) can measure dementia severity in Medicare claims. This cross-sectional study included the National Health and Aging Trends Study Round 5 participants with possible or probable dementia whose Medicare claims were available. We estimated the Functional Assessment Staging Test (FAST) scale (range: 3 [mild cognitive impairment] to 7 [severe dementia]) using information from the survey. We calculated CFI (range: 0-1, higher scores indicating greater frailty) using Medicare claims 12 months prior to the participants' interview date. We examined C-statistics to evaluate the ability of the CFI in identifying moderate-to-severe dementia (FAST stage 5-7) and determined the optimal CFI cut-point that maximized both sensitivity and specificity. Of the 814 participants with possible or probable dementia and measurable CFI, 686 (72.2%) patients were ≥75 years old, 448 (50.8%) were female, and 244 (25.9%) had FAST stage 5-7. The C-statistic of CFI to identify FAST stage 5-7 was 0.78 (95% confidence interval: 0.72-0.83), with a CFI cut-point of 0.280, achieving the maximum sensitivity of 76.9% and specificity of 62.8%. Participants with CFI ≥0.280 had a higher prevalence of disability (19.4% vs 58.3%) and dementia medication use (6.0% vs 22.8%) and higher risk of mortality (10.7% vs 26.3%) and nursing home admission (4.5% vs 10.6%) over 2 years than those with CFI <0.280. Our study suggests that CFI can be useful in identifying moderate-to-severe dementia from administrative claims among older adults with dementia.

Structural and microstructural thalamocortical network disruption in sporadic behavioural variant frontotemporal dementia

BackgroundUsing multi-block methods we combined multimodal neuroimaging metrics of thalamic morphology, thalamic white matter tract diffusion metrics, and cortical thickness to examine changes in behavioural variant frontotemporal dementia. (bvFTD). MethodTwenty-three patients with sporadic bvFTD and 24 healthy controls underwent structural and diffusion MRI scans. Clinical severity was assessed using the Clinical Dementia Rating scale and behavioural severity using the Frontal Behaviour Inventory by patient caregivers. Thalamic volumes were manually segmented. Anterior and posterior thalamic radiation fractional anisotropy and mean diffusivity were extracted using Tract-Based Spatial Statistics. Finally, cortical thickness was assessed using Freesurfer. We used shape analyses, diffusion measures, and cortical thickness as features in sparse multi-block partial least squares (PLS) discriminatory analyses to classify participants within bvFTD or healthy control groups. Sparsity was tuned with five-fold cross-validation repeated 10 times. Final model fit was assessed using permutation testing. Additionally, sparse multi-block PLS was used to examine associations between imaging features and measures of dementia severity. ResultsBilateral anterior-dorsal thalamic atrophy, reduction in mean diffusivity of thalamic projections, and frontotemporal cortical thinning, were the main features predicting bvFTD group membership. The model had a sensitivity of 96%, specificity of 68%, and was statistically significant using permutation testing (p = 0.012). For measures of dementia severity, we found similar involvement of regional thalamic and cortical areas as in discrimination analyses, although more extensive thalamo-cortical white matter metric changes. ConclusionsUsing multimodal neuroimaging, we demonstrate combined structural network dysfunction of anterior cortical regions, cortical-thalamic projections, and anterior thalamic regions in sporadic bvFTD.

Distinguishing apathy and depression in dementia: A longitudinal study.

Apathy is a common symptom in dementia, though can be difficult to distinguish from depression due to shared features and frequent co-occurrence. As such, a significant limitation of much previous research on apathy is the failure to control for depression. The current study sought to address this by examining the trajectory and clinical correlates of apathy after controlling for depression. Seven hundred and seventy-nine patients with dementia were recruited from nine memory clinics around Australia. Measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden and medication use were completed at baseline and at regular intervals over a 3-year period. Driving and institutionalisation data were obtained throughout the study. Mortality data were obtained from state registries 8 years after baseline. Of the 662 patients with completed measures of neuropsychiatric symptoms, 342 (51.7%) had apathy and 332 (50.2%) had depression at baseline, while 212 (32.0%) had both. Whereas apathy increased over time, depression remained relatively stable. Apathy, but not depression, was associated with greater dementia severity, poorer cognition and function, driving cessation and mortality. Both apathy and depression were associated with greater neuropsychiatric symptoms, psychosis, caregiver burden and institutionalisation. Apathy increases over the course of dementia and is associated with worse clinical outcomes independent of depression. Distinguishing apathy and depression appears important given their different implications for prognosis and management.

Trajectories of socio-emotional functioning in early-stage dementia: implications for the individual with dementia and their family carer

Background and objectives Changes in socio-emotional functioning in people living with dementia (PLWD) are common; however, little is known about the broader effects these may have on wellbeing. This study examined socio-emotional functioning over time and associations with the wellbeing of PLWD and their family carers. Method One hundred and one individuals with a diagnosis of dementia and their respective carers completed the Social Emotional Questionnaire (assessing emotion recognition, empathy, social relationships and social behaviour) alongside measures of dementia severity, cognition, mood, stress, and relationship quality. Sixty-six dyads were reassessed on the same measures at 12 months post-baseline, and 51 dyads again at 20 months post-baseline. Results When rated by the PLWD, there was no change in socio-emotional functioning over time; however, carers reported a significant decline over time. For both carers and the PLWD, poorer wellbeing measures were indicative of worse socio-emotional functioning at Time 1, though only dementia type, quality of life and relationship quality impacted upon the trajectory of socio-emotional decline over time. Conclusions Changes in social and emotional functioning are evident early in the course of dementia and worsen within 20 months. Both carer characteristics and those of the PWLD affected reporting of social and emotional functioning. These data are useful for guiding the provision of appropriate education and care.

Predictors of rate of cognitive decline in patients with amnestic mild cognitive impairment

Objective Amnestic mild cognitive impairment (MCI) is a known risk factor for conversion to Alzheimer’s disease (AD). Although substantial research has been conducted on the general profile of amnestic MCI subjects and predictors of conversion to AD, research on predictors of rate of decline has been considerably less extensive. The present study sought to more systematically and comprehensively examine predictors of rate of cognitive decline in a longitudinal sample of individuals with MCI, including age, genetic vulnerability, baseline cognitive performance, and baseline neuropsychiatric severity. Method Participants with single or multi-domain amnestic MCI (N = 151) were assessed at baseline and for a mean of 1.32 follow-up visits (mean interval from baseline to last follow-up = 1.61 years). Results Results showed that carriers of the ApoE ε4 allele declined more quickly on all three dementia severity measures compared to non-carriers. Older individuals did not decline more rapidly in dementia severity. Participants with lower executive functions composite scores and greater memory impairment severity at baseline predicted faster decline on dementia severity measures. Contrary to hypotheses, those with lower levels of depression at baseline declined more rapidly on dementia severity measures compared to those with higher levels of depression. Conclusion Identifying potential predictors of rate of decline from amnestic MCI to AD could be clinically meaningful for prognostic purposes, understanding risk and protective factors, as well as guiding future treatments and clinical trials that could aim to target and delay progression among those patients who are vulnerable to more quickly convert to AD.

THE RELATIONSHIP BETWEEN COGNITION, FUNCTIONAL ABILITIES, AND THE LATENT DEMENTIA PHENOTYPE AMONG CENTENARIANS

Adequate assessment of cognitive abilities and functional capacity is essential for a diagnosis of dementia. However, cognition is only moderately related to functional status, and this relationship is poorly understood among centenarians, a group of older adults with high risk for dementia. A bifactor structural equation model can be used to delineate the variance attributed to dementia-specific related cognitive changes (i.e., the latent variable delta) and the variance due to general intelligence (i.e., g’). This study aimed to determine the validity of delta as a marker of cognitive decline among centenarians. It was hypothesized that delta was correlated with cognitive status, functional abilities and, dementia severity. Overall, 244 community dwelling centenarians (Mage = 100.58, 84.8% female) were recruited through the Georgia Centenarian Study, a population-based study of octogenarians and centenarians from northern Georgia. Older adults were administered measures of cognition and a self-report measure of functional abilities. Latent variable scores (i.e., g’ and delta) were modeled and correlated with standard global cognitive screening measures (i.e., MMSE) and measures of dementia severity. Results indicate that delta was significantly correlated with functional ability and cognitive abilities. Consistent with our hypotheses, delta was also significantly related to dementia severity. Overall, estimates of the latent dementia phenotype, delta, were significantly related to cognitive and functional abilities among centenarians, providing validation of delta as a useful index of dementia severity.

δ Scores Identify Subsets of "Mild Cognitive Impairment" with Variable Conversion Risks.

The latent variable "δ" (for "dementia) is a transdiagnostic measure of dementia severity. δ can be reified and applied to individuals as a composite "d-score". Like Spearman's general intelligence factor "g", δ can be constructed from almost any cognitive battery. So many are available that we must further distinguish each composite as a δ "homolog". Fourteen have been validated. All are strongly associated with dementia severity and potentially with mild cognitive impairment (MCI) conversion. To assess δ's impact on MCI conversion risk. A new δ homolog (dDx) was constructed in 1,230 Mexican-American (MA) and 2,215 non-Hispanic White (NHW) participants in the Texas Alzheimer's Research and Care Consortium (TARCC). 1,445 normal controls (NC) and 723 MCI were followed annually for up to 6 years. Each SD decrease in the dDx score increased the risk of conversion sixteen-fold [OR = 16.39 (CI: 5.0-52.6)]. Cases below the optimal diagnostic threshold for Alzheimer's disease (AD) versus NC were labeled as having a functionally salient cognitive impairment (FSCI). Such cases were at a 73-fold increase risk of a diagnosis of AD [OR = 73.19 (95% CI: 58.3-92.0)]. However, 25.6% of MCI cases were also FSCI(+). They accounted disproportionately for prospective conversions. Age <80 years, the absence of an ɛ4 allele, <12 years of education, and MA ethnicity independently increased the risk of diagnosing FSCI as MCI. A sizable minority of MCI cases may be misdiagnosed and they account disproportionately for AD conversions.

Predictors of Driving Cessation in Dementia: Baseline Characteristics and Trajectories of Disease Progression.

A diagnosis of dementia implies the eventual need to relinquish driving. This is associated with significant morbidity and anticipating when it will need to occur can be important for planning. Patients, however, vary in the course of their disease. We sought to identify predictors of driving cessation in patients with dementia, including both baseline characteristics and changes in cognition and function over time as indicators of disease trajectory. A total of 779 patients with dementia were recruited from 9 memory clinics around Australia. Patients and their carers reported their driving status and completed measures of dementia severity, cognition, function, neuropsychiatric symptoms, and medication use at regular intervals over a 3-year period. Of the 247 patients still driving at baseline, 147 (59.5%) stopped driving during the study. Variables that predicted driving cessation included older age; female sex; greater dementia severity and cognitive and functional impairments at baseline; and greater increases in dementia severity and cognitive and functional impairments over 3 and 6 month periods. The findings confirm that easily assessable characteristics, including changes over time, predict future driving status. The findings underscore the value of regularly assessing patients with standardized measures to determine disease trajectory and likely prognosis.

Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer's disease.

BackgroundAlzheimer’s disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration. However, despite extensive clinical and genomic studies, the molecular basis of AD development and progression remains elusive.MethodsTo elucidate molecular systems associated with AD, we developed a large scale gene expression dataset from 1053 postmortem brain samples across 19 cortical regions of 125 individuals with a severity spectrum of dementia and neuropathology of AD. We excluded brain specimens that evidenced neuropathology other than that characteristic of AD. For the first time, we performed a pan-cortical brain region genomic analysis, characterizing the gene expression changes associated with a measure of dementia severity and multiple measures of the severity of neuropathological lesions associated with AD (neuritic plaques and neurofibrillary tangles) and constructing region-specific co-expression networks. We rank-ordered 44,692 gene probesets, 1558 co-expressed gene modules and 19 brain regions based upon their association with the disease traits.ResultsThe neurobiological pathways identified through these analyses included actin cytoskeleton, axon guidance, and nervous system development. Using public human brain single-cell RNA-sequencing data, we computed brain cell type-specific marker genes for human and determined that many of the abnormally expressed gene signatures and network modules were specific to oligodendrocytes, astrocytes, and neurons. Analysis based on disease severity suggested that: many of the gene expression changes, including those of oligodendrocytes, occurred early in the progression of disease, making them potential translational/treatment development targets and unlikely to be mere bystander result of degeneration; several modules were closely linked to cognitive compromise with lesser association with traditional measures of neuropathology. The brain regional analyses identified temporal lobe gyri as sites associated with the greatest and earliest gene expression abnormalities.ConclusionsThis transcriptomic network analysis of 19 brain regions provides a comprehensive assessment of the critical molecular pathways associated with AD pathology and offers new insights into molecular mechanisms underlying selective regional vulnerability to AD at different stages of the progression of cognitive compromise and development of the canonical neuropathological lesions of AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0355-3) contains supplementary material, which is available to authorized users.

Predictors of Mortality in Dementia: The PRIME Study.

Dementia is a terminal illness. While various baseline characteristics of patients, such as age, sex, and dementia severity, are known to predict mortality, little research has examined how changes in patients' symptoms over time predict survival. There are also limited data on patients seen in memory clinics, as opposed to other health care settings, and whether antipsychotic medications are associated with mortality in dementia once patients' demographic and clinical features are controlled for. To identify predictors of mortality in patients with dementia. Of 970 patients recruited from nine memory clinics around Australia, 779 patients had dementia at baseline. Patients completed measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use at baseline and at regular intervals over a three-year period. Mortality data were obtained from state registries eight years after baseline. Overall, 447 (57.4%) of the patients with dementia died within the eight years. Older age, male sex, more severe dementia and functional impairment at baseline, greater decline in dementia severity and functional impairment over six months, taking a larger number of medications, and use of atypical antipsychotic medication predicted earlier mortality. The findings confirm that demographic and diagnostic features predict the survival of patients with dementia. Importantly, the findings indicate that changes in dementia severity and functional impairment over time predict mortality independently of baseline levels, and provide further evidence for the higher mortality risk of patients taking antipsychotic medications.

Predictors of Institutionalization in Dementia: A Three Year Longitudinal Study

Patients with dementia often require institutionalization when they can no longer care for themselves. The study examined demographic and clinical variables that predict the time until institutionalization in patients with dementia attending memory clinics. Of 970 patients recruited from nine memory clinics around Australia, 779 patients had dementia at baseline. Measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use were completed for all patients. Patients were followed for three years. Overall, 197 (25.3%) of the patients with dementia were institutionalized within three years. Lower cognitive ability, lower functional ability, and more neuropsychiatric symptoms at baseline predicted a shorter time until institutionalization, as did use of antipsychotic medication. In addition, greater deterioration in cognitive ability, functional ability, and neuropsychiatric symptoms over the initial three months predicted a shorter time to institutionalization. The findings confirm that clinical features of dementia at baseline predict the time to institutionalization, as do greater changes in symptoms over three months independent of baseline levels.

Modeling causes of aggressive behavior in patients with dementia.

To examine factors predicting development of aggression in patients with dementia as a step toward developing preventive strategies and nonpharmacologic therapies. Study participants were 171 nonaggressive, community-residing VA patients aged more than 60, newly diagnosed with dementia. Patients and caregivers were assessed at baseline and at months 5, 9, 13, 17, 21, and 25. Aggression was evaluated using the Cohen-Mansfield Agitation Inventory. Survival models incorporating direct and indirect effects were conducted to estimate associations between psychosocial factors (baseline and change measures of dementia severity, pain, depression, caregiver burden, patient-caregiver relationship, and nonaggressive physical agitation) and time to aggression onset. Higher levels of baseline caregiver burden, worst pain, declining patient-caregiver relationship, and increasing nonaggressive physical agitation predicted increased risk of aggression. Baseline dementia severity and depression were indirectly related to onset of aggression. The association between increasing nonaggressive physical agitation and time to aggression onset was independent of the associations between our psychosocial measures and time to aggression onset. Potentially mutable factors were associated with development of aggression. The longitudinal design of this study and its sample of newly diagnosed, previously nonaggressive dementia patients strengthen prior findings in the literature.

Propiedades psicométricas y utilidad diagnóstica del Addenbrooke's Cognitive Examination-Revised (ACE-R) en una muestra de ancianos chilenos

The Addenbrooke's Cognitive Examination - Revised (ACE-R) is a good alternative to the Mini Mental State Examination (MMSE) for assessing cognitive capacities in dementia. To estimate the psychometric properties and diagnostic utility of the Addenbrooke's Cognitive Examination-Revised (ACE-R) in a Chilean elderly sample. ACE-R was adapted for the Chilean population (ACE-R-Ch) and then administered to 60 dementia patients, 22 mild cognitive impairment (MCI) patients and 45 control subjects in addition to the MMSE for assessing global cognitive efficiency. Caregivers of dementia patients and collateral sources of MCI patients and elderly subjects without dementia were interviewed with measures of dementia severity, functional status in activities of daily living and cognitive changes. Convergent validity, internal consistency reliability, cutoff points, sensitivity and specificity for ACE-R-Ch were estimated. Regarding convergent validity, the ACE-R-Ch showed significant correlations (p < 0,001) with another cognitive measure (r = 0,952 with MMSE), a rating for dementia severity (Spearman rho=-0,822 with CDR), functional capacity assessments (r = -0,70 with ADLQ-Ch; r = -0,725 with PFAQ-Ch; and r = 0,650 with IADL Scale) and a measure of cognitive changes (r = -0,633 with AD8-Ch). In terms of reliability, the test had a Cronbach alpha coefficient of 0.918. The best cut-off point to distinguish cases of dementia from control subjects was a score of 76, which reached a sensitivity of 0.92 and a specificity of 0.93. The ACE-R-Ch showed acceptable psychometric properties, becoming a valid and reliable instrument to assess global cognitive efficiency or cognitive impairment. Its diagnostic utility to detect dementia patients also worked very well in a Chilean elderly sample.

Within-Session Practice Effects in Patients Referred for Suspected Dementia

Background: Practice effects are improvements in cognitive test performance associated with repeated administrations of same or similar measures and are traditionally seen as error variance. However, there is growing evidence that practice effects provide clinically useful information. Methods: Within-session practice effects (WISPE) across 2 h were collected from 61 non-consecutive patients referred for suspected dementia and compared to the Mini Mental Status Examination (MMSE), a screening measure of dementia severity. Results: In all patients, WISPE on two cognitive measures were significantly correlated with MMSE, even after controlling for baseline cognitive scores (partial r = 0.47, p < 0.001; partial r = 0.26, p = 0.046). In patients diagnosed with probable Alzheimer’s disease, the trend was even stronger (partial r = 0.72, p < 0.01; partial r = 0.58, p = 0.046). In both groups, lower WISPE were associated with lower MMSE scores (i.e. greater dementia severity), even after controlling for initial cognitive scores. Conclusion: If future research validates these findings with longitudinal studies, then WISPE may have important clinical applications in dementia evaluations.

Association of ApoE and LRP mRNA levels with dementia and AD neuropathology

Inheritance of the ε4 allele of apolipoprotein E (ApoE) is the only confirmed and consistently replicated risk factor for late onset Alzheimer's disease (AD). ApoE is also a key ligand for low-density lipoprotein (LDL) receptor-related protein (LRP), a major neuronal low-density lipoprotein receptor. Despite the considerable converging evidence that implicates ApoE and LRP in the pathogenesis of AD, the precise mechanism by which ApoE and LRP modulate the risk for AD remains elusive. Moreover, studies investigating expression of ApoE and LRP in AD brain have reported variable and contradictory results. To overcome these inconsistencies, we studied the mRNA expression of ApoE and LRP in the postmortem brain of persons who died at different stages of dementia and AD-associated neuropathology relative to controls by quantitative polymerase chain reaction (qPCR) and Western blotting analyses. Clinical dementia rating scores were used as a measure of dementia severity, whereas, Braak neuropathological staging and neuritic plaque density were used as indexes of the neuropathological progression of AD. ApoE and LRP mRNA expression was significantly elevated in the postmortem inferior temporal gyrus (area 20) and the hippocampus from individuals with dementia compared with those with intact cognition. In addition to their strong association with the progression of cognitive dysfunction, LRP and ApoE mRNA levels were also positively correlated with increasing neuropathological hallmarks of AD. Additionally, Western blot analysis of ApoE protein expression in the hippocampus showed that the differential expression observed at the transcriptional level is also reflected at the protein level. Given the critical role played by LRP and ApoE in amyloid beta (Aβ) and cholesterol trafficking, increased expression of LRP and ApoE may not only disrupt cholesterol homeostasis but may also contribute to some of the neurobiological features of AD, including plaque deposition.

Sample Size Requirements for Training to a κ Agreement Criterion on Clinical Dementia Ratings

The Clinical Dementia Rating (CDR) is a valid and reliable global measure of dementia severity. Diagnosis and transition across stages hinge on its consistent administration. Reports of CDR ratings reliability have been based on 1 or 2 test cases at each severity level; agreement (kappa) statistics based on so few rated cases have large error, and confidence intervals are incorrect. Simulations varied the number of test cases, and their distribution across CDR stage; to derive the sample size yielding a 95% confidence that estimated is at least 0.60. We found that testing raters on 5 or more patients per CDR level (total N=25) will yield the desired confidence in estimated kappa, and if the test involves greater representation of CDR stages that are harder to evaluate, at least 42 ratings are needed. Testing newly trained raters with at least 5 patients per CDR stage will provide valid estimation of rater consistency, given the point estimate for kappa is roughly 0.80; fewer test cases increases the standard error and unequal distribution of test cases across CDR stages will lower kappa and increase error.

Increased expression of cholesterol transporter ABCA1 is highly correlated with severity of dementia in AD hippocampus

To gain insight into ATP-binding cassette transporter A1 ( ABCA1) function and its potential role in AD pathology, we analyzed the expression of the cholesterol transporter ABCA1 in postmortem hippocampus from persons at different stages of dementia and AD associated neuropathology relative to cognitively intact normal donors by quantitative polymerase chain reaction (qPCR) and Western blot. In this study clinical dementia rating (CDR) scores were used as a measure of dementia severity, whereas, Braak neuropathological staging and neuritic plaque density were used as an index of the neuropathological progression of AD. Correlation analysis showed that ABCA1 mRNA expression was significantly elevated at the earliest recognizable stage of dementia compared to persons with intact cognition. ABCA1 mRNA was also positively correlated with Braak neuropathological stages and neuritic plaque density counts. Additionally, ABCA1 mRNA levels showed robust correlation with dementia severity even after controlling for the confounding contribution of accompanying neuropathological parameters to ABCA1 mRNA expression. Western blot analyses showed that the differential expression observed at the transcriptional level is also reflected at the protein level. Thus, our study provides transcriptional and translational evidence that the expression of ABCA1, a key modulator of cholesterol transport across the plasma membrane, is dysregulated in the AD brain and that this dysregulation is associated with increasing severity of AD, whether measured functionally as dementia severity or neuropathologically as increased neuritic plaque and neurofibrillary tangle density.

Item analysis of ADAS-Cog: effect of baseline cognitive impairment in a clinical AD trial.

We explored the association of Alzheimer's disease (AD) Assessment Scale (ADAS-Cog) item scores with AD severity using cross-sectional and longitudinal data from the same study. Post hoc analyses were performed using placebo data from a 12-month trial of patients with mild-to-moderate AD (N =281 randomized, N =209 completed). Baseline distributions of ADAS-Cog item scores by Mini-Mental State Examination (MMSE) score and Clinical Dementia Rating (CDR) sum of boxes score (measures of dementia severity) were estimated using local and nonparametric regressions. Mixed-effect models were used to characterize ADAS-Cog item score changes over time by dementia severity (MMSE: mild =21-26, moderate =14-20; global CDR: mild =0.5-1, moderate =2). In the cross-sectional analysis of baseline ADAS-Cog item scores, orientation was the most sensitive item to differentiate patients across levels of cognitive impairment. Several items showed a ceiling effect, particularly in milder AD. In the longitudinal analysis of change scores over 12 months, orientation was the only item with noticeable decline (8%-10%) in mild AD. Most items showed modest declines (5%-20%) in moderate AD.

Apathy and depressive mood in nursing home patients with early-onset dementia.

The study explored whether apathy and depressive mood symptoms (DMS) are related to cognitive and functional features of dementia in 63 nursing home (NH) residents with early-onset dementia (EOD). All EOD residents from one NH (n = 41) and a random sample from another NH were assessed for depressive symptoms (Montgomery Asberg Depression Rating Scale [MADRS]), apathy (Neuropsychiatric Inventory [NPI]), global cognitive functions (Mini-Mental State Examination [MMSE]), activities of daily living (ADL, Minimum Data Set-Resident Assessment Instrument [MDS-RAI]), and overall dementia severity (Global Deterioration Scale [GDS]). DMS were not associated with apathy and dementia severity. Regression analyses adjusted for age, gender, the type of dementia, and DMS revealed that dementia severity measures accounted, respectively, for 14% (ADL), 13% (GDS), and 9% (MMSE) of the variance in apathy. In line with previous research in older patients, the higher apathy scores were associated with more cognitive and functional problems in EOD.