Interactions between weight loss and plasma neurodegenerative markers for determining cognitive decline among community-dwelling older adults

This study aimed to investigate the interaction between weight loss (WL) and plasma amyloid-β42/40 (Aβ42/40), neurofilament light chain (NfL), progranulin, and their association with cognitive decline over time among older adults. This 5-year observational approach included 470 participants from the Multidomain Alzheimer Preventive Trial (MAPT), mean age 76.8y (SD=4.5), 59.4% women. WL was defined as ≥5% decrease over the first year. Biomarkers were measured at 12 months. Cognitive function was assessed yearly from 12 months onwards by Mini-Mental State Examination (MMSE); Clinical Dementia Rating sum of boxes (CDR-SB); a composite score based on Category Naming Test, Digit Symbol Substitution Test, ten MMSE orientation items (MMSEO) and Free and total recall of the Free and Cued Selective Reminding test; and these tests individually. Twenty-seven participants (5.7%) presented WL. In adjusted analyses, combined WL+lower Aβ42/40 (≤0.103, lowest quartile) was related with more pronounced 4-year cognitive decline according to CDR-SB (p<0.0001) and MMSEO (p=0.021), compared to non-WL+higher Aβ42/40. WL+higher NfL (>94.55pg/mL, highest quartile) or progranulin (>38.4ng/mL, three higher quartiles) were related with higher cognitive decline according to CDR-SB, MMSE, MMSEO and composite score (all p<0.03), compared to non-WL+lower NfL or higher progranulin. Regrouping progranulin quartiles (Q1-Q3 vs. Q4) revealed higher cognitive decline among the WL+lower progranulin group compared to non-WL+lower progranulin. In conclusion, 1-year WL was associated with subsequent higher 4-year cognitive decline among older adults presenting low Aβ42/40 or high NfL. Future studies combining plasma biomarker assessments and body weight surveillance may be useful for identifying people at risk of cognitive impairment.

Associations Between Cognitive Function, Depression, and Olfactory Function in Elderly People With Dementia in Korea

Early detection is important for delaying or preventing cognitive impairment. Since olfactory dysfunction and depression are common symptoms of cognitive dysfunction, they may serve as measurable risk indicators. This study was designed to identify the relationship between olfaction, depression, and each domain of cognitive function in elderly dementia patients in South Korea. Study participants were 108 patients who visited the outpatient clinic between March and September 2019. More significant impairment of olfactory function was found in those with mild (7.48 ± 1.28) or moderate (7.37 ± 2.22) test scores of the Expanded Clinical Dementia Rating (CDR) scale than in those with questionable scores (20.58 ± 6.18). The language domain of cognitive function, age, and education level showed 39.2% explanatory power for olfactory function (F = 5.591, p < 0.001). It is expected that assessment of olfactory function in elderly people can lead to the early detection, diagnosis, and treatment of dementia. Furthermore, it is important for future studies to confirm the relationship between each domain of cognitive function and olfactory function according to the type of dementia and to establish criteria for screening dementia in order to utilize olfactory function as a clinical marker.

Plasma MCP-1 and changes on cognitive function in community-dwelling older adults

Background Monocyte Chemoattractant Protein-1 (MCP-1), a glial-derived chemokine, mediates neuroinflammation and may regulate memory outcomes among older adults. We aimed to explore the associations of plasma MCP-1 levels (alone and in combination with β-amyloid deposition—Aβ42/40) with overall and domain-specific cognitive evolution among older adults. Methods Secondary analyses including 1097 subjects (mean age = 75.3 years ± 4.4; 63.8% women) from the Multidomain Alzheimer Preventive Trial (MAPT). MCP-1 (higher is worse) and Aβ42/40 (lower is worse) were measured in plasma collected at year 1. MCP-1 in continuous and as a dichotomy (values in the highest quartile (MCP-1+)) were used, as well as a dichotomy of Aβ42/40. Outcomes were measured annually over 4 years and included the following: cognitive composite z-score (CCS), the Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) sum of boxes (overall cognitive function); composite executive function z-score, composite attention z-score, Free and Cued Selective Reminding Test (FCSRT - memory). Results Plasma MCP-1 as a continuous variable was associated with the worsening of episodic memory over 4 years of follow-up, specifically in measures of free and cued delayed recall. MCP-1+ was associated with worse evolution in the CCS (4-year between-group difference: β = −0.14, 95%CI = −0.26, −0.02) and the CDR sum of boxes (2-year: β = 0.19, 95%CI = 0.06, 0.32). In domain-specific analyses, MCP-1+ was associated with declines in the FCSRT delayed recall sub-domains. In the presence of low Aβ42/40, MCP-1+ was not associated with greater declines in cognitive functions. The interaction with continuous biomarker values Aβ42/40× MCP-1 × time was significant in models with CDR sum of boxes and FCSRT DTR as dependent variables. Conclusions Baseline plasma MCP-1 levels were associated with longitudinal declines in overall cognitive and episodic memory performance in older adults over a 4-year follow-up. How plasma MCP-1 interacts with Aβ42/40 to determine cognitive decline at different stages of cognitive decline/dementia should be clarified by further research. The MCP-1 association on cognitive decline was strongest in those with amyloid plaques, as measured by blood plasma Aβ42/40.

FATORES ASSOCIADOS À SOBRECARGA E QUALIDADE DE VIDA DE CUIDADORES DE IDOSOS COM DEMÊNCIA

O presente estudo objetivou analisar os fatores associados à sobrecarga e qualidade de vida de cuidadores de idosos com demência a partir das características do idoso e do cuidador. Trata-se de um estudo transversal, realizado na cidade de Maceió, Alagoas. A amostra foi composta por 170 indivíduos, 85 pares cuidador/idoso, sendo os idosos com diagnóstico de síndrome demencial e seus respectivos cuidadores principais. A coleta foi realizada por meio de entrevistas com aplicação de escalas validadas. Foi avaliada a sobrecarga e a qualidade de vida do cuidador, através da escala Zarit Burden Interview e do Whoqol-bref, respectivamente, e o estado cognitivo e capacidade funcional dos idosos com a Clinical Dementia Rating (CDR) e o Índice de Katz. Para os cuidadores, predominou o sexo feminino (88,2%), com média de idade de 51,9 (± 12,0), estado civil casado (55,3%), nível educacional acima de nove anos de estudo (77,6%) e renda per capita de até um salário (43,6%). A maior média de qualidade de vida foi encontrada no domínio físico e a menor no ambiental. Encontrou-se relação estatisticamente significativa entre a capacidade funcional e a sobrecarga. Correlação inversa estatisticamente significativa foi evidenciada entre sobrecarga e qualidade de vida. Os achados desta pesquisa sugerem que o declínio funcional dos idosos com demência mostrou exercer influência sobre a sobrecarga dos cuidadores principais, onde foi identificado maior sobrecarga com níveis intermediários de demência.

Construct Validity and Psychometric Properties of the Tamil (India) Version of Montreal Cognitive Assessment (T-MoCA) in Elderly

Background: The Montreal Cognitive Assessment (MoCA) is a neuropsychological cognitive tool developed and adapted widely in various languages for screening mild cognitive impairment (MCI). Objectives: The present study aimed to evaluate the psychometric properties of the Tamil (India) Version of MoCA (T-MoCA) and further examine the construct validity of the tool.Method: The authors conducted internal consistency, test-retest, sensitivity-specificity, and construct validity using 233 Tamil-speaking elderly participants. The inclusion criteria of the study participants were 0.5 or less than 0.5 scores in the Clinical Dementia Rating scale (CDR). Further, T-MoCA was used to screen MCI. Results: The result showed that the T-MoCA had high internal consistency (0.83) and high test-retest reliability (0.92). Receiver operating characteristic (ROC) analyses showed an area under the curve (AUC) of 0.91 (95% CI 0.87-0.94) for detecting MCI. Furthermore, the optimal cut-off score to detect MCI was 24, accommodated a sensitivity and specificity of 88.4% and 77.9%, respectively. Conclusions: The Tamil (India) version of the MoCA maintained its core diagnostic properties, furnishing it a valid and reliable tool for the screening of MCI. Also, its latent dimensions help to understand the elders’ cognitive function in a better way.

Association of Plasma Oligomerized Amyloid-β and Cerebral White Matter Lesions in a Health Screening Population

Background: Cerebral white matter lesions (WML) are related to a higher risk of vascular and Alzheimer’s dementia. Moreover, oligomerized amyloid-β (OAβ) can be measured from blood for dementia screening. Objective: We aimed to investigate the relationship of plasma OAβ levels with clinical and radiological variables in a health screening population. Methods: WML, other volumetric parameters of magnetic resonance images, cognitive assessment, and plasma OAβ level were evaluated. Results: Ninety-two participants were analyzed. The majority of participants’ clinical dementia rating was 0 or 0.5 (96.7%). White matter hyperintensities (WMH) increased with age, but OAβ levels did not (r2 = 0.19, p < 0.001, r2 = 0.03, p = 0.10, respectively). No volumetric data, including cortical thickness/hippocampal volume, showed any significant correlation with OAβ. Log-WMH volume was positively correlated with OAβ (r = 0.24, p = 0.02), and this association was significant in the periventricular area. White matter signal abnormalities from 3D-T1 images were also correlated with the OAβ in the periventricular area (p = 0.039). Multivariate linear regression showed that log-WMH values were independently associated with OAβ (B = 0.879 (95% confidence interval 0.098 –1.660, p = 0.028)). Higher tertiles of WMH showed higher OAβ levels than lower tertiles showed (p = 0.044). Using a cutoff of 0.78 ng/mL, the high OAβ group had a larger WMH volume, especially in the periventricular area, than the low OAβ group (p = 0.036). Conclusion: Both WML and plasma OAβ levels can be early markers for neurodegeneration in the healthcare population. The lesions, especially in the periventricular area, might be related to amyloid pathogenesis, which strengthens the importance of WML in the predementia stage.

Alteration of the corpus callosum in patients with Alzheimer’s disease: Deep learning-based assessment

Background Several studies have reported changes in the corpus callosum (CC) in Alzheimer’s disease. However, the involved region differed according to the study population and study group. Using deep learning technology, we ensured accurate analysis of the CC in Alzheimer’s disease. Methods We used the Open Access Series of Imaging Studies (OASIS) dataset to investigate changes in the CC. The individuals were divided into three groups using the Clinical Dementia Rating (CDR); 94 normal controls (NC) were not demented (NC group, CDR = 0), 56 individuals had very mild dementia (VMD group, CDR = 0.5), and 17 individuals were defined as having mild and moderate dementia (MD group, CDR = 1 or 2). Deep learning technology using a convolutional neural network organized in a U-net architecture was used to segment the CC in the midsagittal plane. Total CC length and regional magnetic resonance imaging (MRI) measurements of the CC were made. Results The total CC length was negatively associated with cognitive function. (beta = -0.139, p = 0.022) Among MRI measurements of the CC, the height of the anterior third (beta = 0.038, p <0.0001) and width of the body (beta = 0.077, p = 0.001) and the height (beta = 0.065, p = 0.001) and area of the splenium (beta = 0.059, p = 0.027) were associated with cognitive function. To distinguish MD from NC and VMD, the receiver operating characteristic analyses of these MRI measurements showed areas under the curves of 0.65–0.74. (total CC length = 0.705, height of the anterior third = 0.735, width of the body = 0.714, height of the splenium = 0.703, area of the splenium = 0.649). Conclusions Among MRI measurements, total CC length, the height of the anterior third and width of the body, and the height and area of the splenium were associated with cognitive decline. They had fair diagnostic validity in distinguishing MD from NC and VMD.

Dementia and autopsy-verified causes of death in racially-diverse older Brazilians

Background While dementia has been associated with specific causes of death, previous studies were relatively small autopsy series or population-based studies lacking autopsy confirmation and were restricted to Non-Latinx Whites. Here, we examine the association of dementia with autopsy-verified causes of death in racially-diverse older Brazilians. Methods As part of the Pathology, Alzheimer´s and Related Dementias Study (PARDoS), a community-based study in Brazil, we included 1941 racially-diverse deceased, 65 years or older at death. We conducted a structured interview with legal informants including the Clinical Dementia Rating (CDR) Scale for dementia proximate to death. Causes of death were assessed after full-body autopsy and macroscopic examination of the brain, thoracic and abdominal/pelvic organs. Up to four causes of death were reported for each decedent. Causes of death were classified as circulatory, infectious, cancer and other. Logistic regression was used to determine associations of dementia with cause of death, controlling for age, sex, race, and education. Results Dementia was associated with a higher odds of an infectious cause of death (OR = 1.81, 95%CI:1.45–2.25), and with a lower odds of a circulatory disease as cause of death (OR = 0.69, 95%CI:0.54–0.86) and cancer as cause of death (OR = 0.41, 95%CI:0.24–0.71). Dementia was associated with a higher odds of pneumonia (OR = 1.92, 95%CI:1.53–2.40) and pulmonary embolism (OR = 2.31, 95%CI:1.75–3.05) as causes of death and with a lower odds of acute myocardial infarction (OR = 0.42, 95%CI:0.31–0.56) and arterial disease (OR = 0.76, 95%CI:0.61–0.94) as causes of death. Conclusion Racially-diverse older Brazilians with dementia had a higher odds of an infectious cause of death and a lower odds of cancer and circulatory disease as causes of death than those without dementia.

Association of Lipidomics Signatures in Blood with Clinical Progression in Preclinical and Prodromal Alzheimer’s Disease

Background: Lipidomics may provide insight into biochemical processes driving Alzheimer’s disease (AD) pathogenesis and ensuing clinical trajectories. Objective: To identify a peripheral lipidomics signature associated with AD pathology and investigate its potential to predict clinical progression. Methods: We used Bayesian elastic net regression to select plasma lipid classes associated with the CSF pTau/Aβ42 ratio as a biomarker of AD pathology in preclinical and prodromal AD cases from the ADNI cohort. Consensus clustering of the selected lipid classes was used to identify lipidomic endophenotypes and study their association with clinical progression. Results: In the APOE4-adjusted model, ether-glycerophospholipids, lyso-glycerophospholipids, free-fatty acids, cholesterol esters, and complex sphingolipids were found to be associated with the CSF pTau/Aβ 42 ratio. We found an optimal number of five lipidomic endophenotypes in the prodromal and preclinical cases, respectively. In the prodromal cases, these clusters differed with respect to the risk of clinical progression as measured by clinical dementia rating score conversion. Conclusion: Lipid alterations can be captured at the earliest phases of AD. A lipidomic signature in blood may provide a dynamic overview of an individual’s metabolic status and may support identifying different risks of clinical progression.

Evaluating Residual Cognition in Advanced Cognitive Impairment: The Residual Cognition Assessment

<b><i>Background:</i></b> In nursing homes, most of the patients with dementia are affected by severe cognitive disorder. Care interventions follow an accurate and recurring multidimensional assessment, including cognitive status. There is still a need to develop new performance-based scales for moderate-to-advanced dementia. <b><i>Objectives:</i></b> The development of the Residual Cognition Assessment (RCA) responds to the need to create new scales for global cognitive screening in advanced dementia, with some peculiar features: performance based, brief (&#x3c;5 m), available without specific training, and suitable for nonverbal patients with minimal distress. <b><i>Methods:</i></b> Two raters have administered the RCA and the Severe Impairment Battery-short version (SIB-S) to 84 participants with MMSE = 0. After 2–3 weeks, the same sample has been retested. The RCA has been also administered to 40 participants with MMSE 1–10 for a comparison. <b><i>Results:</i></b> The RCA has exhibited excellent values for test-retest reliability (intraclass correlation [ICC] = 0.956) as well as for inter-rater reliability (ICC = 0.997). The concurrent validity analyzes have shown strong correlations between the RCA and the SIB-S with ρ = 0.807 (<i>p</i> &#x3c; 0.01), and the RCA and the Clinical Dementia Rating (CDR) with ρ = −0.663 (<i>p</i> &#x3c; 0.01). Moderate correlation has been found between the RCA and the Functional Assessment Staging Scale with ρ = −0.435 (<i>p</i> &#x3c; 0.01). The instrument has showed high internal reliability, too (total: <i>α</i> = 0.899). The RCA has low floor effect (2%) with respect to the SIB-S (58%) but shows ceiling effect in the MMSE 1–10 sample (50%). The ROC curve analyses demonstrate that the RCA is acceptably able to discriminate between subjects with CDR 4/5 with an AUC of 0.92. Exploratory factor analysis shows 3 factors, defined as three major degrees of cognitive performance in advanced dementia, indeed hierarchically structured in three possible levels of decline. <b><i>Conclusions:</i></b> The RCA has showed excellent validity and reliability as well as good sensitivity to identify advanced cognitive impairment in dementia, without floor effect. The RCA seems complementary to the MMSE, so advisable when the latter reaches 0. Administration and scoring are simple, and only few minutes are required to assess the patient. The RCA can discriminate at least 3 different major stages in advanced dementias: severe, profound, and late.