Lower Mini-Mental State Exam Scores Research Articles

Cognitive profile in burning mouth syndrome versus mild cognitive impairment: A comparative study.

This study aims to assess and contrast cognitive and psychological aspects of patients with burning mouth syndrome (BMS-MCI) and geriatric patients (G-MCI) with mild cognitive impairment, focusing on potential predictors like pain, mood disorders, blood biomarkers, and age-related white matter changes (ARWMCs). The study enrolled 40 BMS-MCI and 40 geriatric G-MCI, matching them by age, gender, and educational background. Participants underwent psychological, sleepiness, and cognitive assessment including the Mini-Mental State Exam (MMSE), Trail Making Test (TMT), Corsi Block-Tapping Task, Rey Auditory Verbal Learning Test, Copying Geometric Drawings Test, Frontal Assessment Battery, and Digit Cancellation Test. G-MCI patients exhibited higher ARWMCs scores in right (p = 0.005**) and left (p < 0.001**) temporal regions, which may relate to specific neurodegenerative processes. Conversely, BMS-MCI patients showed higher levels of depression and anxiety and lower MMSE scores(p < 0.001**), also struggling more with tasks requiring processing speed and executive function, as evidenced by their higher TMT-A scores (p < 0.001**). The study highlights particular deficits in global cognition and processing speed for BMS-MCI. The influence of educational background, pain levels, cholesterol, sleep disturbances, and anxiety on these cognitive assessments underscores the need for personalized therapeutic strategies addressing both cognitive and emotional aspects of MCI.

Alzheimer’s Disease (AD): Vitamin B12 deficiency is associated with lower Mini‐Mental State Exam (MMSE) scores

AbstractBackgroundAlzheimer’s Disease (AD) is the leading cause of dementia in the elderly and several lines of evidence indicate that B12 hypovitaminosis is linked to AD. The biochemical pathways involved in AD that are affected by vitamin B12 are APP processing, Aβ fibrillization, Aβ‐induced oxidative damage as well as tau hyperphosphorylation and tau aggregation.Method103 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their vitamin B12 levels assessed and MMSE scores evaluated.Result91 patients (88,35%) presented vitamin B12 normal range (200 – 800 pg/mL) and 12 patients (11,65%) presented vitamin B12 deficiency (≤ 200 pg/mL). From the normal range group, 13 patients (14,29%) presented severe cognitive impairment (MMSE &lt; 10), 33 patients (36,26%) presented moderate cognitive impairment (MMSE = 10 – 20) and 45 patients (49,45%) presented mild cognitive impairment (MMSE &gt; 20). From the deficiency group, 2 patients (16,8%) presented severe cognitive impairment, 5 patients (41,6%) presented moderate cognitive impairment and 5 patients (41,6%) presented mild cognitive impairment. Both groups, vitamin B12 normal range and deficiency, had on average the same educational level: 2,91 and 3,42 years, respectively.ConclusionIn this sample of patients with AD, B12 hypovitaminosis is associated with lower MMSE scores when compared to vitamin B12 normal range.

Alzheimer’s Disease (AD): High cholesterol is associated with lower Mini‐Mental State Exam (MMSE) scores

AbstractBackgroundAlzheimer’s Disease (AD) is the leading cause of dementia in the elderly. The epsilon 4 allele of the apolipoprotein E gene that encodes the major brain lipid carrier and metabolic disorders, such as obesity and type 2 diabetes, were identified as AD risk factors, suggesting that abnormal lipid metabolism could influence the progression of the disease. Additionally, lowering cholesterol is associated with reduced central nervous system (CNS) amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies.Method154 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their cholesterol levels assessed and MMSE scores evaluated.Results90 patients (58,44%) presented high cholesterol (total cholesterol level ≥ 190 mg/dL and/or LDL level ≥ 130 mg/dL) and 64 patients (41,56%) presented cholesterol normal range (total cholesterol level &lt; 190 mg/d L and/or LDL level &lt; 130 mg/dL). From the high cholesterol group, 10 patients (11,11%) presented severe cognitive impairment (MMSE &lt; 10), 50 patients (55,55%) presented moderate cognitive impairment (MMSE = 10 – 20) and 30 patients (33,34%) presented mild cognitive impairment (MMSE &gt; 20). From the cholesterol normal range group, 5 patients (7,81%) presented severe cognitive impairment, 19 patients (29,69%) presented moderate cognitive impairment and 40 patients (62,5%) presented mild cognitive impairment. Both groups, high cholesterol and cholesterol normal range, had on average the same educational level: 2,91 and 3,42 years, respectively.ConclusionIn this sample of patients with AD, high cholesterol is associated with lower MMSE scores when compared to cholesterol normal range.

CAREGIVING BURDENS OF TASK TIME AND TASK DIFFICULTY AMONG PAID AND UNPAID CAREGIVERS OF PERSONS LIVING WITH DEMENTIA

Abstract Demands of caregivers of persons living with dementia (PLWD) are often influenced by the context of their caregiving situation. This study examines factors associated with caregiving burden in terms of task time and task difficulty among paid and unpaid caregivers of PLWD. Cross-sectional baseline survey data were analyzed from 110 paid and unpaid caregivers of PLWD participating in a larger NIH-funded study assessing the feasibility of using a novel in-situ sensor system. Oberst Caregiving Burden Scale constructs of task time and task difficulty served as dependent variables. Two least squares regression models were fitted, controlling for contextual items related to the caregiver, care recipient, and caregiving logistics. Caregivers whose care recipients were female (B=-0.29, P=0.006), had more chronic conditions (B=0.31, P=0.011), and had lower Mini-Mental State Exam scores (B=-0.20, P=0.015) reported higher task time burdens. Caregivers whose care recipients had other paid caregivers (B=0.30, P=0.031) and spent more months/years caring for their care recipients (B=0.28, P=0.004) reported higher task time burdens. Caregivers’ task time burden was positively associated with their emotional stress level (B=0.30, P=0.020). Caregivers’ task difficulty burden was positively associated with their emotional stress (B=0.30, P=0.029) and depressive symptomatology (B=0.32, P=0.002). Results reinforce the relationship between caregiver burden and mental health. While the care recipient’s disease profile and needs were drivers of task time burden, which may also require coordination with other paid caregivers, task difficulty was emotionally driven. Findings highlight the importance of caregiver support services and programming for mental health.

Associations between plasma Neurofilament Light Chain (NfL), Sleep Quality and Cognition in individuals with autosomal‐dominant Alzheimer's Disease (ADAD): Findings from the Colombia‐Boston (COLBOS) biomarker study

AbstractBackgroundMethods available for in‐vivo diagnosis of Alzheimer's disease (AD) are expensive and invasive. Neurofilament light chain (NfL), a plasma‐based biomarker for neurodegeneration, is a promising marker for early detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non‐carrier family members twenty years before the onset of clinical symptoms. Here, we examined whether baseline levels of plasma NfL predict self‐reported sleep quality and cognition 10 years later in non‐demented PSEN1‐E280A carriers and non‐carriers. MethodsA total of 51 PSEN1‐E280A carriers (mean age = 30.06, SD = 4.63), including 2 mildly impaired carriers and 49 age‐matched non‐carriers (mean age = 35.55, SD = 6.16) from the Colombia‐Boston (COLBOS) longitudinal biomarker study were included. Participants underwent blood sampling at baseline and completed the Pittsburgh Sleep Quality Index (PSQI), Mini Mental State Exam (MMSE), and memory testing (CERAD Word List) at follow‐up approximately 10 years later. Self‐reported sleep quality was assessed by calculating the PSQI score. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Linear regressions were used to examine associations among NfL levels, sleep quality, and memory.ResultsThere were no group differences, between carriers and non‐carriers, in baseline NfL levels, memory performance, or total PSQI scores (p&gt;0.05). However, carriers had lower MMSE scores than non‐carriers (carriers M=27.90; non‐carriers M=28.47; p = 0.05). Among the entire sample, baseline NfL levels predicted recall scores on the CERAD word list (p = 0.03) and MMSE performance (p = 0.02). Additionally, associations between NfL levels and age trended toward significance (p = 0.06). Sleep quality (PSQI) was not associated with age, memory performance, or NfL levels.ConclusionsPreliminary findings support the hypothesis that plasma NfL levels may predict memory function and overall cognitive status in ADAD. However, our findings suggest that NfL levels may not be associated with self‐reported sleep quality in individuals in prodromal stages of ADAD. Future work using objective sleep metrics and larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.

Intracranial internal carotid artery calcification is not predictive of future cognitive decline

BackgroundIntracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia.MethodsIn a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR > 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers.ResultsBaseline ICA calcium score could not distinguish participants who converted to CDR > 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume.ConclusionsIn elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease.

Alzheimer’s Disease (AD): Sarcopenia is associated with lower Mini‐Mental State Exam (MMSE) scores

AbstractBackgroundSarcopenia is highly prevalent in dementia, regardless of sarcopenia definition and irrespective of continent of study. According to the systematic review and meta‐analysis conducted by Chang et al. (2016), sarcopenia is independently associated with cognitive impairment.Methods195 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their sarcopenia levels assessed in consonance with the European Working Group on Sarcopenia in Older People (EWGSOP) and MMSE scores evaluated.Results55 out of 195 patients (28,20%) were diagnosed with sarcopenia (Low Mass Muscle ‐ LMM plus Low Muscle Strength – LMS or Low Physical Performance – LPP). From the sarcopenia group 4 patients (7,28%) presented severe cognitive impairment (MMSE &lt; 10), 25 patients (45,45%) presented moderate cognitive impairment (MMSE = 10 – 20) and 26 patients (47,27%) presented mild cognitive impairment (MMSE &gt; 20). From the non‐sarcopenia group 11 patients (7,86%) presented severe cognitive impairment, 45 patients (32,14%) presented moderate cognitive impairment and 84 patients (60%) presented mild cognitive impairment. Both groups, sarcopenia and non‐ sarcopenia, had on average the same educational level: 2,93 and 3,66 years respectively.ConclusionIn this sample of patients with AD, sarcopenia is associated with lower MMSE scores when compared to non‐sarcopenia.

Cognitive impairment in adult CHD survivors: A pilot study

The most common comorbidities in children with congenital heart disease (CHD) are neurodevelopmental impairments, particularly in areas of executive function, memory and attention. Limited studies have demonstrated similar impairments in CHD adults although no studies have screened specifically for mild cognitive impairment and dementia. Methods We performed a prospective cross-sectional study of CHD patients, ages 30-65 years, who were coming for clinic visits. We administered the Mini-Mental State Exam (MMSE), and scores were compared with population norms adjusted by age and education level. Results A total of 125 patients were recruited (55% male). The median age was 40 years (range 30-65). More than a half (80%) had some college education or advanced degrees. Adjusting for age and education, CHD participants scored significantly lower than the general population (median 1 point lower, p<0.001) on the MMSE. The greatest impairments occurred in recall and orientation. Five percent of the total cohort met the general threshold for mild cognitive impairment (MMSE < 24). Clinical factors associated with this degree of cognitive impairment were duration of cyanosis (p=0.005) and decreased systemic ventricular function (p=0.003). Conclusions Our pilot study showed that, when adjusted for age and education level, CHD adults had significantly lower MMSE scores than the general population, with 5% meeting criteria for mild cognitive impairment. These findings suggest that subtle and early cognitive changes are present in the adult CHD population. Further studies are needed to investigate those changes that might influence long-term outcomes in the adult CHD population.

Racial comparisons of MRI and PiB PET in acute stroke

AbstractBackgroundStroke and Alzheimer disease share risk factors and often co‐occur, and both have been reported to have a higher prevalence in African‐Americans. However, the interaction of race, stroke, and Alzheimer disease has not been established.MethodWe compared MRI and PiB PET biomarkers of non‐demented participants with and without acute ischemic stroke (total n=243, age 65‐101), with a focus on comparing African‐Americans (n=42 with stroke, n=84 without) to Non‐Hispanic Whites (n=39 with stroke, n=78 without). Our assessment included radiologic reads of the number of large infarcts, small infarcts, microbleeds, and leukoaraiosis; a PET measure of amyloid binding; quantitative measures of hippocampal volume and white matter hyperintensities; and longitudinal Mini Mental State Exam (MMSE) scores. Statistical analysis used logistic regression models to predict each biomarker using race and stroke status, while controlling for age, family history, APOE4, education, sex, and high blood pressure.ResultPiB PET did not differ significantly by stroke status or by race, with 23.6% of participants being classified as amyloid positive (Figure 1). As expected in stroke, the acute stroke participants were more likely to have large infarcts, small infarcts, microbleeds, and non‐zero Fazekas scores. MMSE showed racial differences at baseline (mean 26.8 for African‐Americans, 27.9 for Non‐Hispanic Whites, p=0.03), but not longitudinally. Overall, African‐Americans were more likely to have microbleeds (32.8% vs 22.6%, p=0.04). Within the stroke group African‐Americans were more likely to have small infarcts (75.6% vs 56.8%, p=0.049). Combined, African‐Americans were also more likely to have more than 5 microbleeds ‐ the cutoff for many Alzheimer clinical trials (15.2% vs 9.6%, p=0.04).ConclusionPreclinical Alzheimer disease does not appear to be a risk factor for stroke and did not differ by race in our sample. Standard clinical MRI measures differed by stroke status, but showed few racial differences. The observed lower MMSE scores in African‐Americans has been reported previously and may arise for a variety of reasons. In individuals with stroke, African‐Americans may have more severe pathology as evidenced by greater numbers of small infarcts and microbleeds. African‐Americans may be more likely to be excluded from Alzheimer disease clinical trials due to having 5 or more microbleeds.

Abstract 14215: Cognitive Impairment in Adult Congenital Heart Disease Survivors: A Pilot Study

Introduction: The most common comorbidities in children with congenital heart disease (CHD) are neurodevelopmental and psychosocial impairments, particularly in areas of executive function, memory, attention, and behavioral control. Limited studies in the adult CHD population suggest similar impairments exist and adults with CHD may be at increased risk for dementia. No studies have screened specifically for mild cognitive impairment and dementia in adult CHD patients. Methods: We performed a prospective cross-sectional study of adult CHD patients, ages 30-65 years, who were coming for routine clinic visits. We administered the Mini-Mental State Exam (MMSE) and scores were compared with population norms adjusted by age and education level. We also evaluated the association of MMSE scores with CHD complexity, demographic and clinical risk factors. Results: A total of 125 patients were recruited (55% male). The median age was 40 years (range 30-65). Almost all participants (97%) had a high school degree and 75% had some college education or advanced degrees. The majority of patients (94%) had moderate or complex CHD. Adjusting for age and education, CHD participants scored significantly lower than the general population (median 1 point lower, p=0.001). The greatest impairments occurred in recall and orientation. Factors associated with lower scores included decreased systemic ventricular function (p=0.028) and having ≥2 cardiac catheterizations (p=0.006). Five percent of the total cohort met the general threshold for mild cognitive impairment (MMSE&lt;24). Clinical factors associated with this degree of cognitive impairment were duration of cyanosis (p=0.005) and decreased systemic ventricular function (p=0.003). Conclusions: Our pilot study showed that, when adjusted for age and education level, adult CHD patients had significantly lower MMSE scores than the general population, with 5% meeting criteria for mild cognitive impairment. These findings suggest that subtle and early neurodevelopmental changes are present in the adult CHD population. Further studies are needed to investigate those changes and evaluate potential disease modifying therapies that might influence long-term outcomes in the adult CHD population.

Overlap Between Apolipoprotein Eε4 Allele and Slowing Gait Results in Cognitive Impairment.

Background: Although apolipoprotein E polymorphism ε4 allele (ApoE4) and slow gait are well-known risk factors for cognitive impairment, examination of their combined effect on cognitive function is lacking. Our objective was to elucidate whether a combination of ApoE4 phenotyping and slow gait resulted in greater cognitive impairment.Methods: Overall, 1,085 community-dwelling older adults, either ApoE4 carriers (n = 167, 15.4%) or non-ApoE4 carriers, were included from the “Takashimadaira study.” Gait speed was assessed with an electronic walkway and slow gait was defined as <1 m/s. Cognitive performance was also assessed using the Mini-Mental State Exam (MMSE) and the Trail Making Test (TMT)-A and -B. A two-way analysis of covariance (ANCOVA; ApoE and gait velocity factors) adjusted for covariates was performed for each analysis.Results: Gait and cognitive performances were similar for ApoE4 and non-ApoE4 carriers. A two-way ANCOVA of the MMSE showed a significant interaction between the two factors. ApoE4 carriers with slow gait had lower MMSE scores than ApoE4 carriers without slow gait and non-ApoE4 carriers with slow gait. Also, a significant main effect of gait velocity on TMT-A was observed, indicating that slow gait is associated with lower scores irrespective of the presence of ApoE4. There was no main effect or interaction observed on the TMT-B.Conclusions: Our results suggest that the concurrent presence of at least one copy of ApoE4 and slow gait can define a subgroup with the lowest cognition. Elucidating the mechanisms underlying these associations may point out modifiable factors in populations at risk of dementia.

Association of Cognitive Function with Amyloid-β and Tau Proteins in the Vitreous Humor.

The eye may serve as source for diagnostic testing for early detection of Alzheimer's disease (AD). Examination of amyloid-β (Aβ) and tau protein content in human vitreous and its correlation to neuro-cognition may improve ocular-based AD detection methods. To evaluate levels of Aβ and tau protein in human vitreous humor and investigate the clinical predictive role of these proteins as early diagnostic markers of AD. A prospective, single-center, multi-surgeon cohort study. Vitreous humor samples from 80 eyes were measured quantitatively for Aβ40-42, pTau, and tTau. Linear regression was used to test associations between AD biomarker levels, Mini-Mental State Exam (MMSE), and serum apolipoprotein E (APOE) allele status, with adjustment for age, sex, and education level of patients. Lower MMSE scores were significantly associated with lower levels of vitreous Aβ40 (p = 0.015), Aβ42 (p = 0.0066), and tTau (p = 0.0085), and these biomarkers were not associated with any pre-existing eye conditions. Presence of the ɛ4 allele and the ɛ2 allele approached significance with reduced Aβ40 level (p = 0.053) and increased p-Tau level (p = 0.056), respectively. Patients with poor cognitive function have significantly lower vitreous humor levels of AD-related biomarkers Aβ40, Aβ42, and tTau. These biomarkers do not correlate with underlying eye conditions, suggesting their specificity in association with cognitive change. This is the first study to our knowledge to correlate cognition with AD-related proteins in the vitreous humor. Results suggest ocular proteins may have a role for early dementia detection in individuals at risk for AD.

Early Detection of Lower MMSE Scores in Elderly Based on Dual-Task Gait

The dual-task paradigm is a promising procedure for estimating cognitive status and may also be collaterally used to reduce cognitive decline and prevent dementia. In this paper, we use the mini-mental state exam (MMSE) to the assess cognitive status in the elderly as a reference and investigate the potential of using machine learning for early detecting cognitive impairment in the elderly. Although many studies have suggested that dual-task performance, in which participants perform a cognitive task while walking, is associated with cognition, they only considered the correlation between cognitive parameters and simple gait feature, such as gait speed, through the statistical analysis. We instead use a Kinect sensor to capture participants' whole-body movements and extract a rich gait feature that has the ability to exhibit different tendencies of movements between healthy and cognitive-impaired elderlies. In our experiments, a classifier based on the dual-task gait feature achieved a higher performance than the one based on the single-task feature; the performance of the rich gait feature was better than that of a simple one, and; an optimal detection performance was achieved with an MMSE cutoff score of 25. We positively validated that the proposed method could early detect elderly with lower MMSE scores based on dual-task gait feature with a promising performance. Our approach can support early and automated diagnosis of cognitive impairment.

Association Between Psychosis Phenotype and APOE Genotype on the Clinical Profiles of Alzheimer's Disease.

Psychosis is a common phenomenon in Alzheimer's disease (AD). The APOE ε4 allele is the strongest genetic risk factor for the development of AD, but its association with psychosis remains unclear. We investigated the associations between psychosis, subdivided into delusions and hallucinations, as well as APOE ε4 allele on cognitive and functional outcomes. Secondarily, we investigated the associations between APOE ε4, Lewy bodies, and psychosis. Data from the National Alzheimer's Coordinating Center (NACC) were used. Nine hundred patients with a confirmed diagnosis of AD based on the NIA-AA Reagan were included in the analysis. Global cognition was assessed using the Mini-Mental State Exam (MMSE) and functional status was assessed using the Functional Activities Questionnaire (FAQ). Psychosis status was determined using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Factorial design was used to assess the effects of psychosis and APOE ε4, as well as their interaction. Psychosis and the presence of APOE ε4 were both associated with lower MMSE scores, while only psychosis was associated with higher FAQ scores. Furthermore, patients with hallucinations had lower MMSE and higher FAQ scores than patients with only delusions. There was a significant interaction effect between psychosis and APOE ε4 on MMSE scores, with APOE ε4 negatively affecting patients with hallucinations-only psychosis. APOE ε4 was positively associated with the presence of Lewy body pathology, and both were found to be more prevalent in psychotic patients, with a stronger association with hallucinations. Psychosis in AD was associated with greater cognitive and functional impairments. Patients with hallucinations-with or without delusions-conferred even greater deficits compared to patients with only delusions. The APOE ε4 allele was associated with worse cognition, especially for patients with hallucination-only psychosis. APOE ε4 may mediate cognitive impairment in the hallucinations phenotype through the development of Lewy bodies. Our findings support that subtypes of psychosis should be evaluated separately.

Sleep disturbances and later cognitive status: a multi-centre study

ObjectiveTo investigate the associations between sleep disturbances in mid-life and late-life and late-life cognitive status. MethodsIn four population-based studies (three Swedish studies: H70 study, Kungsholmen Project (KP) and The Swedish Panel Study of Living Conditions of the Oldest Old (SWEOLD); and one Finnish study: Cardiovascular Risk Factors, Aging and Dementia (CAIDE)), participants provided self-reports on insomnia, nightmares and general sleep problems. Late-life cognitive status was measured by the Mini Mental State Exam (MMSE). The associations between late-life sleep disturbances and cognition 3–11 years later were investigated across all studies (n = 3210). Mean baseline ages were 70 (CAIDE, H70 and SWEOLD), and 84 years (KP). Additional analyses examined the association between midlife sleep and late-life cognition using CAIDE (21 and 31 years follow-up, n = 1306, mean age 50 years), and SWEOLD (20–24 years follow-up, n = 2068, mean age 58 years). Ordered logistic regressions, adjusted for potential baseline confounders, were used in the analyses. ResultsLate-life sleep disturbances were associated with poorer cognition after 3–11 years (fully adjusted β = −0.12, 95% CI = −0.24 to −0.01). Midlife nightmares and insomnia were also associated with lower MMSE scores (fully adjusted β = −0.28, 95% CI = −0.49 to −0.07 and β = −0.20, 95% CI = −0.39 to −0.01), although the latter association was attenuated after adjusting for lifestyle/health-related confounders. Midlife general sleep problems were not associated with late-life MMSE performance. ConclusionsSleep disturbances and midlife nightmares were associated with lower MMSE scores, which suggests that sleep disturbances in earlier life stages can be associated with worse late-life cognition.

DIFFERENTIAL INTERACTION OF APOE ε4 AND PSYCHOSIS PHENOTYPES ON COGNITIVE PERFORMANCE IN ALZHEIMER’S DISEASE

Psychosis is a common phenomenon in Alzheimer's disease (AD), with approximately a third of patients developing delusions and a sixth developing hallucinations. The APOE ε4 allele is a well-established genetic risk factor for the development of AD, but its relationship with psychosis remains unclear. Studies to date have produced conflicting results on its impact on the risk of developing psychosis, and no studies have investigated its effect on the clinical profiles of patients who develop psychosis. The current study investigated the relationship between APOEε4 and psychosis on cognitive and functional performance in a large sample of neuropathologically confirmed AD patients. Neuropathologically confirmed (high probability) AD patients based on the NIA-AA Reagan criteria from the National Alzheimer's Coordinating Center database were included in the analysis. The Neuropsychiatric Inventory Questionnaire was used to assess psychosis, categorized as non-psychotic (AD-P) and psychotic (AD+P). AD+P was further divided into delusions-only (AD+D), hallucinations-only (AD+H), or both forms of psychosis (AD+DH). The Mini Mental State Exam (MMSE) was used as a measure of cognitive performance while the Functional Activities Questionnaire (FAQ), was used as a measure of functional performance. Chi-square tests and general linear models were used. Our cohort consisted of 910 AD patients (Figure 1). Psychosis and the presence of one or two copies of APOE ε4 allele were associated with lower MMSE scores (p<0.001, p=0.013, respectively), while only psychosis was associated with higher FAQ scores (p<0.001) after controlling for age and education. Furthermore, AD+H and AD+DH groups had significantly lower MMSE and higher FAQ scores than AD+D. There was a significant interaction effect between APOE ε4 and the psychosis subtype on MMSE (p=0.038): APOEε4 significantly decreased MMSE more in the AD+H group compared to all other groups (Figure2). Psychosis in AD, particularly hallucinations, is associated with greater cognitive and functional deficits. The APOE ε4 allele is also associated with greater cognitive deficits, with a significantly more detrimental effect on patients with hallucinations. The results of our analysis suggest that delusions and hallucinations in AD may have separate neurobiology, with distinct clinical profiles and underlying mechanisms. Flow chart showing the number of cases with available data, and the breakdown into psychosis groups. Interactive effect of APOE ε4 allele and psychosis on MMSE scores. The MMSE scores shown are adjusted for covariates age and education.

Drug Burden Index and change in cognition over time in community-dwelling older men: the CHAMP study

Objective: Anticholinergic and sedative medications are associated with acute cognitive impairment, but the long-term impact on change in cognition is unclear. This study investigated the effect of anticholinergic and sedative medications, quantified using the Drug Burden Index (DBI), on change in cognition over time in community-dwelling older men.Methods: This was a prospective cohort study of men aged ≥70 years in Sydney, Australia. DBI was assessed at baseline, 2, and 5 years. Cognitive performance was assessed using the Mini-Mental State Exam (MMSE) at each wave. Logistic quantile mixed-effects modelling was used to assess the adjusted effect of DBI on the median MMSE-time profile. Analyses were restricted to men with English-speaking backgrounds (n = 1059, 862, and 611 at baseline, 2, and 5 years).Results: Overall, 292 (27.7%), 258 (29.9%), and 189 (31.3%) men used anticholinergic or sedative medications at baseline, 2, and 5 years. There was a concave relationship between MMSE and time, where higher DBI corresponded to lower MMSE scores (coefficient: −0.161; 95% CI: −0.250 to −0.071) but not acceleration of declining MMSE over time.Conclusions: Exposure to anticholinergic and sedative medications is associated with a small impairment in cognitive performance but not decline in cognition over time.KEY MESSAGESExposure to anticholinergic and sedative medications, quantified using the Drug Burden Index, is associated with small cross-sectional impairments in cognitive performance.There was no evidence that exposure to anticholinergic and sedative medications is associated with accelerating decline in cognitive performance over a 5-year follow-up.Older people taking anticholinergic and sedative medications may derive immediate but small benefits in cognitive performance from clinical medication reviews to minimize or cease prescribing of these medications.

Misdiagnosis using brief cognitive screening instruments in a population-representative sample

The Affordable Care Act requires physicians to screen older patients for cognitive impairment. The Mini-Mental State Exam (MMSE) has been used widely for this purpose, though frequently a 'one-size-fits-all' score < 24 is used to indicate dementia. Because many factors influence cognitive test performance, a single MMSE cutpoint risks both over and under diagnosis of cognitive impairment. We examined performance of the standard MMSE cutpoint in relation to clinical diagnosis in a population-representative sample that reflects primary care throughout the U.S. Data were from the Aging Demographics and Memory Study (ADAMS), a cognitive aging study including participants aged 70 and older enrolled in the Health and Retirement Study. Participants received a standardized diagnostic protocol with extensive in-home clinical and neuropsychological assessment to determine consensus diagnosis of normal cognition; cognitive impairment, not demented (CIND); or dementia. Our sample included individuals with baseline diagnosis of normal cognition (n = 224) or CIND (n= 187), with 2 to 4 follow-up assessments spanning up to 5.9 years. Using multivariate regression, we assessed the contributions of demographic and genetic factors to MMSE score. MMSE scores ranged from 10–29 for CIND and 17–30 for cognitively normal. At baseline, 12.7% classified as cognitively normal had an MMSE < 24, while 50.6% diagnosed as CIND scored < 24. Overlap of MMSE scores between diagnoses of CIND and normal cognition was 90%. Higher age, less education, male gender, and ethnic minority status was associated with lower MMSE scores in both cognitively normal and CIND. Presence of at least one APOE e4 allele was associated with lower MMSE scores in normal cognition, but not CIND. Combined, these individual differences accounted for 36%-46% of variance in MMSE score, but their contribution did not differ among those who remained stable cognitively, who declined cognitively, or who improved cognitively. Findings in a heterogeneous community sample highlight considerable overlap between normal and impaired cognition on brief cognitive screening instruments. This underscores that performance on these measures should not be interpreted in isolation but are a useful tool for tracking change over time and establishing current cognition in the context of the full clinical history.

Anosognosia Is a Significant Predictor of Apathy in Alzheimer’s Disease

Anosognosia and apathy are among the most common behavioral and psychological disorders of Alzheimer's disease and are significantly associated in cross-sectional studies. The aim for this study was to carry out for the first time a longitudinal assessment of this association with the aim of clarifying the predictive role between anosognosia and apathy in Alzheimer's disease. A consecutive series of 213 patients with probable Alzheimer's disease were assessed for the presence of apathy and anosognosia using a specific neuropsychiatry assessment. One hundred fifty four of the patients (72%) had a follow-up assessment between 1 and 4 years after the baseline evaluation. Patients with anosognosia at baseline had a significant increase in apathy scores during follow-up relative to patients without anosognosia at both assessments. Conversely, patients with or without apathy had an increase of similar magnitude in anosognosia scores. In conclusion, anosognosia is a significant predictor of apathy in Alzheimer's disease. This may be related to a specific pattern of progression of neuropathology and/or to poor adjustment of Alzheimer's disease patients with poor insight into their functional deficits.

Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI)

In mostly small single-center studies, Alzheimer's disease (AD) is associated with characteristic and progressive reductions in fluorodeoxyglucose positron emission tomography (PET) measurements of the regional cerebral metabolic rate for glucose (CMRgl). The AD Neuroimaging Initiative (ADNI) is acquiring FDG PET, volumetric magnetic resonance imaging, and other biomarker measurements in a large longitudinal multi-center study of initially mildly affected probable AD (pAD) patients, amnestic mild cognitive impairment (aMCI) patients, who are at increased AD risk, and cognitively normal controls (NC), and we are responsible for analyzing the PET images using statistical parametric mapping (SPM). Here we compare baseline CMRgl measurements from 74 pAD patients and 142 aMCI patients to those from 82 NC, we correlate CMRgl with categorical and continuous measures of clinical disease severity, and we compare apolipoprotein E (APOE) ɛ4 carriers to non-carriers in each of these subject groups. In comparison with NC, the pAD and aMCI groups each had significantly lower CMRgl bilaterally in posterior cingulate, precuneus, parietotemporal and frontal cortex. Similar reductions were observed when categories of disease severity or lower Mini-Mental State Exam (MMSE) scores were correlated with lower CMRgl. However, when analyses were restricted to the pAD patients, lower MMSE scores were significantly correlated with lower left frontal and temporal CMRgl. These findings from a large, multi-site study support previous single-site findings, supports the characteristic pattern of baseline CMRgl reductions in AD and aMCI patients, as well as preferential anterior CMRgl reductions after the onset of AD dementia.