Pre-dementia States Research Articles

EARLY DETECTION OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS FROM VOICE RECORDINGS: THE FRAMINGHAM HEART STUDY

Abstract With the aging global population and the increasing prevalence of dementia, there is a growing focus on identifying mild cognitive impairment (MCI), a pre-dementia state, to enable timely interventions that could potentially slow down neurodegeneration. Producing speech is a cognitively complex task that engages various cognitive domains, while the ease of audio data collection underscores the potential cost-effectiveness and noninvasiveness that voice may offer. This study aims to construct a machine learning pipeline that incorporates speaker diarization, feature extraction, feature selection, and classification, to identify a set of acoustic features that exhibit strong MCI detection capability. The study included 100 MCI cases and 100 healthy controls (HC) matched for age, sex, and education from the Framingham Heart Study. Participants’ speech responses during cognitive tests were recorded, and the recorded audio was processed to identify segments of each participant’s voice from recordings that included voices of both testers and participants. A comprehensive set of 6385 acoustic features was then extracted from these voice segments using the OpenSMILE and Praat softwares. Subsequently, we constructed a random forest model using the features that exhibited significant differences between the MCI and HC groups. We identified an optimal subset of 29 features that resulted in an AUC of 0.87, with a 90% confidence interval ranging from 0.82 to 0.93. This study showcases the potential of human voice as a valuable resource for improving early detection of ADRD and motivates future opportunities to use passive voice collection tools, such as hearing aids, to measure brain health.

Which Mild Behavioral Impairment‐Checklist (MBI‐C) items discriminate between cognitive diagnoses at baseline and follow‐up? Results from the Compostela Ageing Study (CompAS)

AbstractBackgroundThe Mild Behavioral Impairment Checklist (MBI‐C) is a 34 Neuropsychiatric Symptoms (NPS) checklist for the evaluation of pre‐dementia states. Our aim was to analyze which MBI‐C symptoms could best discriminate between participants with different cognitive outcomes both at baseline and at diagnosis time (after 50‐75 months).MethodA total of 179 participants from the Compostela Aging Study (CompAS) were included in the analyses, 108 identified as Subjective Cognitive Complainers (SCC), 47 diagnosed as Mild Cognitive Impairment (MCI) and 24 diagnosed as dementia. NPS were assessed using the validated Spanish version of the MBI‐C (Mallo et al., 2018) at baseline and 50‐75 months follow‐up. Discriminant analyses were carried out at baseline and follow‐up, being the dependent variable the diagnosis at the follow‐up and the independent variable the MBI‐C scores.ResultThe results of the discriminant analysis at baseline indicated a poor adjustment of the model to the data (Wilk’s lambda = .821; p<.001). At baseline, three items (item 9 “discouraged”, 22 “hoard objects”, and 19 “stubborn/rigid”) discriminate 65% of cases, mostly SCCs (97.2%) (Table 1).The results of the discriminant analysis at follow‐up indicated a much better adjustment of the model to the data (Wilk’s lambda = .468; p<.001) (Table 1).The variance was explained almost exclusively by the first function obtained (53%) while the second only reached 7%. At follow‐up, seven items discriminate between groups (item 4 “unmotivated”, 25 “less sensible”, 26 “talk to strangers”, 21 “food no tasty”, 24 “control difficulties”, 5 “less emotional”, 28 “no social judgement”). These items correctly discriminated the SCC (99%) and the 66.7% of dementia patients, but only 6.8% of the MCI (Figure 1).ConclusionModel fit at baseline was poor, and almost exclusively discriminate SCC. The discrimination power increased as the MBI‐C measure were close to the diagnosis, especially for dementia.Distal prediction of dementia nor predementia states using NPS was not successful though some MBI‐C items showed slight better performance at baseline than in follow‐up.

P152: Early detection and evolution of Mild Behavioral Impairment in a sample of people with subjective cognitive complaints

Objective:Mild behavioral impairment (MBI) is a validated diagnostic entity, that describes the emergence of later life neuropsychiatric symptoms (NPS) in pre-dementia states. The aim of this study was to estimate the prevalence of MBI in people with subjective cognitive complains (SCCs) in primary care centers and observe the evolution in a longitudinal study.Methods:Three hundred twenty-three participants belonging to the CompAS longitudinal study who attended primary care centers with SCCs and without previous diagnosis of dementia and other neurological or psychiatric disturbances underwent clinical, neurological, and neuropsychological examinations at baseline and at two follow-up times (around 24 and 60 moths). At each evaluation point participants were diagnosed as Cognitively Unimpaired (UC), Mild Cognitive Impairment (MCI) and SDC; at the follow-up assessments dementia was diagnosed as well. Diagnosis of MBI was made via a series of semistructured independent interviews with patients and relatives in accordance with the ISTAART-AA criteria and using the Spanish MBI-C cut-off point (Mallo et al, 2019). Frequencies of participants diagnosed in each category were obtained and evolution of the MBI along the follow-up evaluations was studied.Results:MBI diagnosis prevalence was 22.9% at baseline corresponding to 74 individuals of which at 24 months follow-up were MBI stable 31.1%, 14.9% evolved to MCI, 1.3% to dementia and 40% to CU, (attrition 12.2%). At 60 months follow-up, from the 23 individuals with MBI, 6 remained stable (26.1%), 6 (21.1%) evolved to MCI, 2 (8.7%) to dementia, 3 (13%) to CU, (attrition 26.1%) (Figure 1).Conclusions:Results indicated that almost a quarter of individuals attending primary care centers with SCCs without previous diagnosis of dementia or psychiatric disorders are MBI. An important part of them evolve to UC or MCI, and only a minority progress to dementia. More studies are needed to analyze the cognitive, personal, and biological factors that determine this evolution.

The assessment of Mild Behavioral Impairment (MBI): Some methodological issues

Objective:The assessment of MBI involves two important issues: 1) to know the underlying structure of the Mild Behavioral Impairment Checklist (MBI-C) a questionnaire designed to evaluates Neuropsychiatric Symptoms (NPS) in pre-dementia states; and 2) to consider self and proxy (i.e., study partner) symptom ratings that may not capture comparable samples. Our objective is to give some answer to these questions: first, to analyze the underlying structure of the MBI-C at baseline and follow-up using Multidimensional Scaling (MDS) and two, to determine how self and proxy ratings and the choice of rating type impact in the results of the MBI-C.Methods:To analyze MBI-C structure, 200 Subjective Cognitive Decline and Mild Cognitive Impairment patients from the CompAS longitudinal study completed baseline and follow-up assessments. Two-step bidimensional weighted dichotomous MDS were performed. All items were included in the first step. Items closely associated with each dimension (1 SD above or below the mean) were selected in a second step to obtain the final models solution.We will also present a review of the literature on the importance of self and proxy MBI-C ratings. We will also present new empirical evidence based on data from over 10,000 cognitively normal.Results:Results from baseline and follow-up showed two dimensions: Dimension I (right-left) differentiate high and low emotional activation and Dimension II (top-down) high and low behavioral activation. The combination of both generates 4 quadrants: resistance, restlessness, flattening and desolation. The final models were built considering the most relevant items, with little differences between baseline and follow-up. The good fit of the models, type of two-dimensional solution and group weights were similar in baseline and follow-up.Regarding our second objective, the results suggest that self and proxy ratings may not capture comparable samples and that the choice of rating type can indeed impact the conclusions drawn from analysis.Conclusions:The 4 quadrants identified could be the most useful NPS to determine risk factors for predementia patients. Also, the findings suggest that the way of applying the MBI-C has relevant implications.

89 The Effect of Personality Traits on the Development of Predementia Cognitive States: Results from the Einstein Aging Study

Objective:Recent research has found associations between the Five Factor Model (FFM) personality traits (Openness to Experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism) and risk of developing subjective cognitive decline (SCD), mild cognitive impairment (MCI), and/or dementia. It has therefore been proposed that personality should be incorporated into conceptual models of dementia risk, as personality assessments have utility as readily available, low-cost measures to predict who is at greater risk for developing pathological cognitive decline. The objective of the present study was to explore the relationship between FFM personality traits and predementia cognitive syndromes including SCD, amnestic MCI (aMCI), and non-amnestic MCI (naMCI). The first aim was to compare baseline personality traits between participants who transitioned from healthy cognition or SCD to aMCI vs. naMCI. The second aim was to determine the relationship between FFM personality traits and risk of transition between predementia cognitive states. The third aim was to explore relationships between levels of FFM personality traits and performance on a comprehensive cognitive battery.Participants and Methods:The participants for this study were 562 (Aim 3; Mean Age = 78.90) older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment (Aims 1 & 2; Mean Age = 78.60). Baseline levels of FFM personality traits were measured in the EAS using the 50-item International Personality Item Pool (IPIP) version of the NEO-Personality Inventory. Baseline levels of anxiety and depressive symptoms, medical history, performance on a cognitive battery and age sex, and years of education were also collected. A multistate Markov approach was used to model the risk of transition across the four predementia states (cognitively healthy, SCD, aMCI, and naMCI) with each FFM personality trait as covariates.Results:Regarding Aim 1, Mann-Whitney U tests revealed no differences in levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. Regarding Aim 2, the multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, the model revealed that higher levels of extraversion were protective against developing naMCI. Finally, regarding Aim 3, exploratory correlations revealed many positive associations between levels of openness to experience and performance on neuropsychological tests. Few associations were found for the other FFM personality traits.Conclusions:Results from this study suggest that premorbid personality traits may play a predictive role in the risk for or protection against specific predementia syndromes. Thus, FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. These personality measures could be used (in addition to other established risk factors for cognitive decline) to enrich clinical trials by targeting individuals who are at greatest risk for developing specific forms of cognitive decline. Such measures may also be useful in diagnostic prediction models for predementia syndromes. These results should be replicated in future studies with larger sample sizes and younger participants.

Deep medullary veins: a promising neuroimaging marker for mild cognitive impairment in outpatients

Background and purposeMild cognitive impairment is an age-dependent pre-dementia state caused by varied reasons. Early detection of MCI helps handle dementia. Vascular factors are vital for the occurrence of MCI. This study investigates the correlation between deep medullary veins and multi-dimensional cognitive outcomes.Materials and methodsA total of 73 participants with MCI and 32 controls were enrolled. Minimum Mental State Examination and Montreal Cognitive Assessment were used to examine the global cognitive function, and different cognitive domains were measured by specific neuropsychological tests. MRI was used to assess the visibility of the DMV and other neuroimage markers.ResultsDMV score was statistically significantly higher in the MCI group compared with the control group (P = 0.009) and independently related to MCI (P = 0.007). Linear regression analysis verified that DMV score was linearly related to global cognition, memory, attention, and executive function after adjusting for cerebrovascular risk factors.ConclusionDMV score was independently related to the onset of MCI, and correlates with overall cognition, memory, attention, and executive function in outpatients.

The Cost of Early Diagnosis of Cognitive Decline in German Memory Clinics

Dementias are expensive diseases: the net annual cost in European healthcare is about € 28.000 per case with a strong stage dependency, of which medical care accounts for about 19%. Diagnostic costs, on the other hand, account for only a small proportion of the total costs. With changes in the guidelines, biomarker tests are becoming increasingly important. At present, the concrete economic impact of biomarker-based diagnosis is largely unknown. To determine the actual costs of diagnostic procedures based on guidelines, we conducted a survey among the members of the German Memory Clinic Network (DNG). From 15 expert centres, the staff engagement time for all procedures was collected. Based on the individual engagement times of the different professions, the total of personnel costs for diagnostics was calculated using current gross personnel costs. The total sum of diagnostic costs (personnel plus procedures) was calculated for three different scenarios e. g. € 633,97 for diagnostics without biomarkers, € 1.214,90 for diagnostics with CSF biomarkers and € 4.740,58 € for diagnostics with FDG- plus Amyloid-PET. In addition, the actual diagnostic costs of the current practice in expert memory clinics were estimated, taking into account personnel costs, costs for the different procedures and the frequency of their use across all patients. This results in total average costs of € 1.394,43 per case as the mean across all centres (personnel costs € 351,72, costs for diagnostic procedures € 1.042,71). The results show that state-of-the-art diagnosis of dementia and pre-dementia states, such as mild cognitive impairment (MCI) requires financial resources, which are currently not fully reimbursed in Germany. The need for a biomarker-based etiological diagnosis of dementia and pre-dementia states will increase, due to availability of disease-modifying treatments. Therefore, the current gap of reimbursement must be filled by new models of compensation.

Apathy as a Treatment Target in Alzheimer's Disease: Implications for Clinical Trials

Apathy is one of the most prevalent, stable and persistent neuropsychiatric symptom across the neurocognitive disorders spectrum. Recent advances in understanding of phenomenology, neurobiology and intervention trials highlight apathy as an important target for clinical intervention. We conducted a comprehensive review and critical evaluation of recent advances to determine the evidence-based suggestions for future trial designs. This review focused on 4 key areas: 1) pre-dementia states; 2) assessment; 3) mechanisms/biomarkers and 4) treatment/intervention efficacy. Considerable progress has been made in understanding apathy as a treatment target and appreciating pharmacological and non-pharmacological apathy treatment interventions. Areas requiring greater investigation include: diagnostic procedures, symptom measurement, understanding the biological mechanisms/biomarkers of apathy, and a well-formed approach to the development of treatment strategies. A better understanding of the subdomains and biological mechanisms of apathy will advance apathy as a treatment target for clinical trials.

Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial.

BackgroundCognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent.ObjectiveWe aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia.MethodsParticipants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel–based analyses were used to identify the cognitive improvement–related functional connectivity in the visual network of the brain.ResultsAfter VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group.ConclusionsFully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity.Trial RegistrationClinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa

Hyperconnectivity of Self-Referential Network as a Predictive Biomarker of the Progression of Alzheimer's Disease.

Self-referential processing is associated with the progression of Alzheimer's disease (AD), and cerebrospinal fluid (CSF) proteins have become accepted biomarkers of AD. Our objective in this study was to focus on the relationships between the self-referential network (SRN) and CSF pathology in AD-spectrum patients. A total of 80 participants, including 20 cognitively normal, 20 early mild cognitive impairment (EMCI), 20 late MCI (LMCI), and 20 AD, were recruited for this study. Independent component analysis was used to explore the topological SRN patterns, and the abnormalities of this network were identified at different stages of AD. Finally, CSF pathological characteristics (i.e., CSF Aβ, t-tau, and p-tau) that affected the abnormalities of the SRN were further determined during the progression of AD. Compared to cognitively normal subjects, AD-spectrum patients (i.e., EMCI, LMCI, and AD) showed a reversing trend toward an association between CSF pathological markers and the abnormal SRN occurring during the progression of AD. However, a certain disease state (i.e., the present LMCI) with a low concentration of CSF tau could evoke more hyperconnectivity of the SRN than other patients with progressively increasing concentrations of CSF tau (i.e., EMCI and AD), and this fluctuation of CSF tau was more sensitive to the hyperconnectivity of the SRN than the dynamic changes of CSF Aβ. The integrity of the SRN was closely associated with CSF pathological characteristics, and these findings support the view that the hyperconnectivity of the SRN will play an important role in monitoring the progression of the pre-dementia state to AD.

SUBJECTIVE MEMORY COMPLAINTS AND COGNITIVE PERFORMANCE: THE MODERATING ROLE OF DEPRESSIVE SYMPTOMS

Cognitive health is a rising public health concern in the U.S. Currently, approximately 5.7 million older adults suffer from Alzheimer’s disease (AD), and by the year 2050 this number is expected to increase to 14 million. Subjective memory complaints (SMC) are shown to be an early indicator of cognitive decline, and accordingly included as a clinical criterion for diagnoses of MCI, an indicator of pre-dementia states, and a research criterion for AD diagnoses. Among older adults, depressive symptoms hinder the accuracy of memory self-ratings. However, there has yet to be consensus regarding the nature of how depressive symptoms may condition the relationship between SMC and cognitive performance. The aims of the present study are to both investigate whether SMC is related to episodic memory and to determine whether depressive symptoms act as a moderator for the relationship between SMC and episodic memory among older adults. This research used nationally representative sample of 8,123 older adults aged 65 and older who completed the Leave Behind Questionnaire in the 2012 and 2014 waves of the Health and Retirement Study. Linear regression was performed and results showed that there was a significant main effect of SMC on episodic memory performance, in that older adults with increased SMC have worse episodic memory. There was also a significant moderating effect of depressive symptoms, in that depressive symptoms cause older adults to underestimate their memory abilities. In order to use SMC as a tool for early detection efforts it is critical to understand these complex relationships.

Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota

ObjectiveGut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. BackgroundAD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. New/Updated HypothesisWe hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. Major Challenges for the HypothesisThe diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. Linkage to Other Major TheoriesEscherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram-negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood-brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

Assessing Mild Behavioral Impairment with the Mild Behavioral Impairment-Checklist in People with Mild Cognitive Impairment.

Neuropsychiatric symptoms (NPS) are non-cognitive, behavioral, or psychiatric symptoms, common in mild cognitive impairment (MCI) and associated with a higher risk of dementia. Mild behavioral impairment (MBI) is a validated diagnostic entity, that describes the emergence of later life NPS in pre-dementia states. The Mild Behavioral Impairment Checklist (MBI-C) is the first measure developed to assess MBI. To estimate the prevalence of MBI in people with MCI and to study the score distribution, sensitivity, specificity, diagnostic utility of the MBI-C, and its correlations with neuropsychological tests. One hundred eleven MCI participants were evaluated with the Questionnaire for Subjective Memory Complaints (QSMC), Mini-Mental State Examination, Cambridge Cognitive Assessment-Revised, Neuropsychiatric Inventory-Questionnaire (NPI-Q), Geriatric Depression Scale-15 items (GDS-15), Lawton and Brody Index, and the MBI-C, which was administered by phone to participants' informants. Descriptive, logistic regression, ROC curve, and bivariate correlations analyses were performed. MBI diagnosis prevalence was 14.2%. The total MBI-C score differentiated people with MBI at a cutoff-point of 6.5, optimizing sensitivity and specificity. MBI-C total score correlated positively with NPI-Q, QSMC, GDS-15, and Lawton and Brody Index. The total MBI-C score, obtained by phone administration, is sensitive for detecting MBI in people with MCI. The MBI-C scores indicated that MCI participants had subtle NPS that were correlated to their subjective memory complaints reported by informants, depressive symptoms, and negatively with Instrumental Activities of Daily Living. Further research should be done to clarify the predictive role of NPS in MCI for incident dementia.

SYNERGIC TRIAL (SYNchronizing Exercises, Remedies in Gait and Cognition) a multi-Centre randomized controlled double blind trial to improve gait and cognition in mild cognitive impairment

BackgroundPhysical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy.MethodsThe SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3 × 10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels.DiscussionThe SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI.Trial RegistrationIdentifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676.

Neuropsychiatric symptoms as risk factors of dementia in a Mexican population: A 10/66 Dementia Research Group study

IntroductionCognitive and/or memory impairment are the main clinical markers currently used to identify subjects at risk of developing dementia. This study aimed to explore the relationship between the presence of neuropsychiatric symptoms and dementia incidence. MethodsWe analyzed the association between neuropsychiatric symptoms and incident dementia in a cohort of 1355 Mexican older adults from the general population over 3 years of follow-up, modeling cumulative incidence ratios using Poisson models. ResultsFive neuropsychiatric symptoms were associated with incident dementia: delusions, hallucinations, anxiety, aberrant motor behavior, and depression. The simultaneous presence of two symptoms had a relative risk, adjusted for mild cognitive impairment, diabetes, indicators of cognitive function, and sociodemographic factors, of 1.9 (95% confidence interval, 1.2–2.9), whereas the presence of three to five, similarly adjusted, had a relative risk of 3.0 (95% confidence interval, 1.9–4.8). DiscussionNeuropsychiatric symptoms are common in predementia states and may independently contribute as risk factors for developing dementia.

Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults.

A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI. MBI was assessed in 1,377 older (age range 72-79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory. 34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol. This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

Dual-Task Gait Testing Identifies MCI Patients Likely to Develop Dementia

Easy to administer, noninvasive, and low-cost, dual-task gait testing may capture some subtleties missed by global cognitive methods.

Clinimetric validity of the Trail Making Test Czech version in Parkinson’s disease and normative data for older adults

Objective: The influence of demographic variables on the Trail Making Test (TMT) performance in older individuals and empirical findings on clinical validity in predementia states, such as Parkinson’s disease mild cognitive impairment (PD-MCI), are limited. The principal aim of this study was to add normative data for the Czech population of older adults and explore the clinimetric properties between PD-MCI and PD patients with normal cognition (PD-NC). Method: The study included 125 PD patients classified as 77 PD-MCI and 48 PD-NC and 528 older individuals (60–74 years, further subdivided for normative tables into 60–64, 65–69 and 70–74 age groups) and very old individuals (aged 75–96, further subdivided into 75–79, 80–84, 85–96) cognitively intact Czech adults. Results: Mostly age, to a lesser extent education but not gender, was associated with most TMT basic and derived indices (TMT-B – A). However, the ratio of TMT-B/TMT-A was independent of both age and education. We provide corresponding T-scores that minimize the effect of demographic variables. The results showed a high discriminative validity of TMT basic and derived indices for the differentiation of PD-MCI from PD-NC (all p < .05). The classification accuracy for the differentiation of PD-MCI from controls was optimal for the TMT-B only (80% area under the curve) based on norm adjusted scores. The classification accuracy of the TMT for PD-MCI vs. PD-NC was suboptimal. Conclusions: The cut-offs and normative standards are useful in clinical practice for those working with PD patients and very old adults.

Prevalence, neurobiology, and treatments for apathy in prodromal dementia.

Apathy, characterized by diminished motivation, is a highly prevalent neuropsychiatric symptom in dementia. However, there is a substantial knowledge gap with regard to prevalence rates, neurobiological underpinnings, and effective treatments for apathy in pre-dementia states, including mild cognitive impairment (MCI) and mild behavioral impairment (MBI). We conducted a comprehensive literature search using MEDLINE, Embase, and PsycINFO databases to identify available research on apathy in prodromal dementia. Apathy has consistently been detected in individuals with MCI with varying prevalence rates, and only recently has literature discussed the prevalence of apathy in MBI. Few pharmacological treatments have been utilized for apathy, with galantamine and risperidone showing mild reductions in apathetic behaviors. Non-pharmacological interventions in prodromal dementia are beginning to be explored and show promise, but few studies have replicated those results. More comprehensive guidelines for diagnosing apathy and further research investigating neurobiological mechanisms of apathy in MCI and MBI are required in order to effectively treat apathetic patients in prodromal dementia.

A parsimonious scoring and normative calculator for the Parkinson’s disease mild cognitive impairment battery

Objective: The aim of the present study was to provide a regression-based calculator that takes premorbid functioning into account to detect subtle cognitive decline, as is often present in pre-dementia states, especially mild cognitive impairment in Parkinson’s disease (PD-MCI).Method: We used demographic adjustments based on sex, age, and education of 699 normative participants that fulfilled exclusion criteria for ascertaining the diagnostic accuracy of the Movement Disorders Society PD-MCI battery at Level II. We examined the clinical validity of the battery on 36 PD patients.Results: An estimated z-score was calculated for any raw score based on different models that adjust for the demographic predictors of gender, age, and education, either concurrently, individually or without covariates. We provide a useful online z-score, SD, and percentile calculator that yields estimates of cognitive impairment based on normative sample for each of the ten neuropsychological tests and enables actuarial decision-making regarding its level and profile (number of domains impaired). We document the clinical utility and applicability of the calculator on a patient with PD-MCI and show the discriminative validity of all measures in the battery by comparing PD-MCI and PD without cognitive impairment with the highest area under the curve (.94) for Tower of London at −2 SD threshold.Conclusions: Our normative calculator introduces a practical web-based psychometric tool for the evaluation of PD-MCI status in clinical settings. We show the detection potential of each of ten measures included in the battery and delineate the diagnostic precision of the PD-MCI battery.