Sex Differences in the Relationship between Depressive Symptoms and Risk of Amnestic Mild Cognitive Impairment.
Ontology highlight
ABSTRACT: The relationship between depressive symptoms and subsequent cognitive impairment in older adults is controversial. Sex differences and the differences in the method of categorizing depressive symptoms may contribute to the inconsistencies. The authors examined the effect of severity of baseline depressive symptoms on risk of incident amnestic mild cognitive impairment (aMCI) separately in men and women.Community-dwelling and cognitively healthy older adults (aged???70 years) from the Einstein Aging Study completed the 15-item Geriatric Depression Scale (GDS-15) at their baseline visit. Participants were categorized into "no/low symptoms" (GDS-15 score?=?0-2), "mild symptoms" (GDS-15 score?=?3-5), and "moderate/severe symptoms" (GDS-15 score?>?6) groups. Sex-stratified Cox proportional hazards models, adjusted for age, education, and antidepressant medication, estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident aMCI as a function of depressive symptoms group.We followed 572 women (mean age: 78) and 345 men (mean age: 77) for 4.2 years on average (range: 1.0-14.6 years). Ninety women and 64 men developed aMCI during follow-up. Cox models revealed that compared with no/low depressive symptoms, mild symptoms were associated with a two times greater risk of developing aMCI in men (HR: 2.22; 95% CI: 1.26-3.89) but not in women (HR: 1.26; 95% CI: 0.77-2.06). Conversely, moderate/severe depressive symptoms were associated with a two times greater risk of developing aMCI in women (HR: 1.99; 95% CI: 1.05-3.77) but not in men (HR: 0.28; 95% CI: 0.04-2.11), possibly because of low statistical power in this subgroup.Results indicate that mild depressive symptoms in men and moderate/severe symptoms in women may represent a marker for future cognitive impairment.
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20160909 1
<h4>Objective</h4>The relationship between depressive symptoms and subsequent cognitive impairment in older adults is controversial. Sex differences and the differences in the method of categorizing depressive symptoms may contribute to the inconsistencies. The authors examined the effect of severity of baseline depressive symptoms on risk of incident amnestic mild cognitive impairment (aMCI) separately in men and women.<h4>Methods</h4>Community-dwelling and cognitively healthy older adults (age ...[more]
Project description:BackgroundOdor identification (OI) deficits are observed in both individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI), and serve as risk factors for dementia. Compared with males, females typically demonstrate superior OI performance and different risks of dementia. However, the role of sex in the relationship between OI dysfunction and cognitive impairment remains uncertain.MethodsIn total, 121 subjects with SCD (41 males and 80 females), and 169 subjects with MCI (59 males and 110 females) underwent the Sniffin' Sticks Screen 16 test and comprehensive neuropsychological examination. The relationships between olfactory and cognitive impairment were analyzed via partial correlation, multiple linear regression and moderating effects.ResultsIn both SCD and MCI subjects, males performed better in language and females performed better in memory. The correlation between OI and cognition tended to be stronger in MCI subjects than in SCD subjects. In MCI subjects, the correlation tended to be stronger in females. For MCI females, better OI performance was correlated with higher short-term memory and attention scores. For MCI males, better OI performance was correlated with higher short-term memory scores. The OI was correlated with language in SCD males and with attention in SCD females. Sex played a moderating role in the relationship between OI dysfunction and language in MCI subjects and the relationship between OI dysfunction and short-term delayed recall memory and language in SCD subjects.ConclusionThese findings revealed significant sex differences between OI dysfunction and cognitive impairment in SCD and MCI subjects. Sex differences should be considered when utilizing OI in clinical settings to predict cognitive function.
Project description:The pathophysiology of amnestic Mild Cognitive Impairment (aMCI) is largely unknown, although some papers found signs of immune activation. To assess the cytokine network in aMCI after excluding patients with major depression (MDD) and to examine the immune profiles of quantitative aMCI (qMCI) and distress symptoms of old age (DSOA) scores. A case-control study was conducted on 61 Thai aMCI participants and 60 healthy old adults (both without MDD). The Bio-Plex Pro human cytokine 27-plex test kit was used to assay cytokines/chemokines/growth factors in fasting plasma samples. aMCI is characterized by a significant immunosuppression, and reductions in T helper 1 (Th)1 and T cell growth profiles, the immune-inflammatory responses system, interleukin (IL)1β, IL6, IL7, IL12p70, IL13, GM-CSF, and MCP-1. These 7 cytokines/chemokines exhibit neuroprotective effects at physiologic concentrations. In multivariate analyses, three neurotoxic chemokines, CCL11, CCL5, and CXCL8, emerged as significant predictors of aMCI. Logistic regression showed that aMCI was best predicted by combining IL7, IL1β, MCP-1, years of education (all inversely associated) and CCL5 (positively associated). We found that 38.2% of the variance in the qMCI score was explained by IL7, IL1β, MCP-1, IL13, years of education (inversely associated) and CCL5 (positively associated). The DSOA was not associated with any immune data. An imbalance between lowered levels of neuroprotective cytokines and chemokines, and relative increases in neurotoxic chemokines are key factors in aMCI. Future MCI research should always control for the confounding effects of affective symptoms.
Project description:BackgroundIt has been established that the overall performance of associative memory was disproportionately impaired in contrast to item memory in aMCI (Amnestic mild cognitive impairment) patients, but little is known about the specific aspects of the memory process that show differences between aMCI and healthy controls. By comparing an item-item associative learning test with an individual item learning test, the present study investigated whether the rate of learning was slower in associative memory than in item memory in aMCI. Furthermore, we examined whether deficits in intertrial acquisition and consolidation contributed to the potential disproportionate impairments in the learning rate of associative memory for aMCI patients. In addition, we further explored whether the aMCI-discriminative power of the associative memory test increases more than that of the item memory test when the number of learning-test trials increases.MethodsA group of 40 aMCI patients and 40 matched control participants were administered a standardized item memory test (Auditory Verbal Learning Test, AVLT) and a standardized associative memory test (Paired Associative Learning Test, PALT), as well as other neuropsychological tests and clinical assessments.ResultsThe results indicated that the learning rate deficits in aMCI patients were more obvious for associative memory than for item memory and that the deficits resulted from impairments in both intertrial acquisition and consolidation. In addition, the receiver operating characteristic curve and logistical regression analysis revealed that the discriminative power of the associative memory test for aMCI was larger than that of the item memory test, especially with more than one learning-test trials.ConclusionsDue to more deficits in learning rate of associative memory than that of item memory, the discriminative power for aMCI tended to be larger in associative memory than in item memory when the number of learning-test trials increased. It is suggested that associative memory tests with multiple trials may be particularly useful for early detection of aMCI.
Project description:Amnestic MCI is often considered an early clinical stage of AD, but its subtle presentation leads to infrequent neurological evaluations. Early plasma biomarker screening during routine check-ups in community hospitals could enhance aMCI detection rates. Advances in proteomics, particularly mass spectrometry, have enabled the detection of low-abundance plasma proteins, opening new possibilities for aMCI biomarker identification. This study included 84 participants from the STAR cohort. We utilized deep plasma proteomics to detect low-abundance proteins, enriched with biofunctional magnetic beads. An early diagnostic model for aMCI was developed through bioinformatics and machine learning, with performance compared to the Simoa assay.
Project description:BackgroundDespite the frequent co-occurrence of depression and diabetes, gender differences in their relationship remain unclear.AimsThis exploratory study examined if gender modifies the association between depressive symptoms, prediabetes and diabetes with cognitive-affective and somatic depressive symptom clusters.MethodCross-sectional analyses were conducted on 29 619 participants from the 2007-2018 National Health and Nutrition Examination Survey. Depressive symptoms were measured by the nine-item Patient Health Questionnaire. Multiple logistic regression was used to analyse the relationship between depressive symptoms and diabetes. Multiple linear regression was used to analyse the relationship between depressive symptom clusters and diabetes.ResultsThe odds of having depressive symptoms were greater in those with diabetes compared to those without. Similarly, total symptom cluster scores were higher in participants with diabetes. Statistically significant diabetes-gender interactions were found in the cognitive-affective symptom cluster model. Mean cognitive-affective symptom scores were higher for females with diabetes (coefficient = 0.23, CI: 0.10, 0.36, P = 0.001) than males with diabetes (coefficient = -0.05, CI: -0.16, 0.07, P = 0.434) when compared to the non-diabetic groups.ConclusionsDiabetes was associated with higher cognitive-affective symptom scores in females than in males. Future studies should examine gender differences in causal pathways and how diabetic states interact with gender and influence symptom profiles.
Project description:BackgroundPrevious work examining normal controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) identified substantial biological heterogeneity. We hypothesized that ADNI mild cognitive impairment (MCI) subjects would also exhibit heterogeneity with possible clinical implications.MethodsADNI subjects diagnosed with amnestic MCI (n=138) were clustered based on baseline magnetic resonance imaging, cerebrospinal fluid, and serum biomarkers. The clusters were compared with respect to longitudinal atrophy, cognitive trajectory, and time to conversion.ResultsFour clusters emerged with distinct biomarker patterns: The first cluster was biologically similar to normal controls and rarely converted to Alzheimer's disease (AD) during follow-up. The second cluster had characteristics of early Alzheimer's pathology. The third cluster showed the most severe atrophy but barely abnormal tau levels and a substantial proportion converted to clinical AD. The fourth cluster appeared to be pre-AD and nearly all converted to AD.ConclusionsSubjects with MCI who were clinically similar showed substantial heterogeneity in biomarkers.
Project description:BackgroundWe tested if rates of brain atrophy accelerate in individuals with amnestic mild cognitive impairment (aMCI) as they progress to typical late onset Alzheimer disease (AD). We included comparisons to subjects with aMCI who did not progress (labeled aMCI-S) and also to cognitively normal elderly subjects (CN).MethodsWe studied 46 subjects with aMCI who progressed to AD (labeled aMCI-P), 46 CN, and 23 aMCI-S. All subjects must have had three or more serial MRI scans. Rates of brain shrinkage and ventricular expansion were measured across all available serial MRI scans in each subject. Change in volumes relative to the point at which subjects progressed to a clinical diagnosis of AD (the index date) was modeled in aMCI-P. Change in volumes relative to age was modeled in all three clinical groups.ResultsIn aMCI-P the change in pre to post index rate (i.e., acceleration) of ventricular expansion was 1.7 cm(3)/year, and acceleration in brain shrinkage was 5.3 cm(3)/year. Brain volume declined and ventricular volume increased in all three groups with age. Volume changes decelerated with increasing age in aMCI-P, and to a lesser extent in aMCI-S, but were linear in the matched CN. Among all subjects with aMCI, rates of atrophy were greater in apolipoprotein E epsilon 4 carriers than noncarriers.ConclusionsRates of atrophy accelerate as individuals progress from amnestic mild cognitive impairment (aMCI) to typical late onset Alzheimer disease (AD). Rates of atrophy are greater in younger than older subjects with aMCI who progressed to AD and subjects with aMCI who did not progress. We did not find that atrophy rates varied with age in 70- to 90-year-old cognitively normal subjects.
Project description:Widespread structural and functional alterations have been reported in the two highly prevalent mild cognitive impairment (MCI) subtypes, amnestic MCI (aMCI) and vascular MCI (VaMCI). However, the changing pattern in functional connectivity strength (FCS) remains largely unclear. The aim of the present study is to detect the differences of FCS and to further explore the detailed resting-state functional connectivity (FC) alterations among VaMCI subjects, aMCI subjects, and healthy controls (HC). Twenty-six aMCI subjects, 31 VaMCI participants, and 36 HC participants underwent cognitive assessments and resting-state functional MRI scans. At first, one-way ANCOVA and post hoc analysis indicated significant decreased FCS in the left middle temporal gyrus (MTG) in aMCI and VaMCI groups compared to HC, especially in the VaMCI group. Then, we selected the left MTG as a seed to further explore the detailed resting-state FC alterations among the three groups, and the results indicated that FC between the left MTG and some frontal brain regions were significantly decreased mainly in VaMCI. Finally, partial correlation analysis revealed that the FC values between the left MTG and left inferior frontal gyrus were positively correlated with the cognitive performance episodic memory and negatively related to the living status. The present study demonstrated that different FCS alterations existed in aMCI and VaMCI. These findings may provide a novel insight into the understanding of pathophysiological mechanisms underlying different MCI subtypes.
Project description:BackgroundAlthough amyloid-β (Aβ) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear.ObjectiveTo examine associations of Aβ and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia.MethodsRestriction spectrum imaging, cerebrospinal fluid Aβ, and longitudinal cognitive data were collected on 23 healthy controls and 13 individuals with mild cognitive impairment or mild to moderate Alzheimer's disease. Neurite density (ND) and isotropic free water diffusion (IF) were computed in fiber tracts and cortical regions of interest. We examined associations of Aβ with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of Aβ on cognitive decline.ResultsLower ND in limbic and association fibers and higher medial temporal lobe IF predicted baseline impairment and longitudinal decline across multiple cognitive domains. ND and IF predicted cognitive outcomes after adjustment for Aβ or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. Aβ correlated with whole-brain, rather than regional, ND and IF.ConclusionAβ correlates with widespread microstructural brain changes, whereas regional microstructure correlates with cognitive decline. Microstructural abnormalities predict cognitive decline regardless of amyloid, and may inform about neural injury leading to cognitive decline beyond that attributable to amyloid.
Project description:The entorhinal cortex is the site of some of the earliest pathological changes in Alzheimer's disease, including neuronal, synaptic and volumetric loss. Specifically, the lateral entorhinal cortex shows significant accumulation of tau neurofibrillary tangles in the amnestic mild cognitive impairment (aMCI) phase of Alzheimer's disease. Although decreased entorhinal cortex activation has been observed in patients with aMCI in the context of impaired memory function, it remains unclear if functional changes in the entorhinal cortex can be localized to the lateral or medial entorhinal cortex. To assess subregion specific changes in the lateral and medial entorhinal cortex, patients with aMCI and healthy aged-matched control participants underwent high-resolution structural and functional magnetic resonance imaging. Patients with aMCI showed significantly reduced volume, and decreased activation localized to the lateral entorhinal cortex but not the medial entorhinal cortex. These results show that structural and functional changes associated with impaired memory function differentially engage the lateral entorhinal cortex in patients with aMCI, consistent with the locus of early disease related pathology.
