Sex Differences in the Relationship between Depressive Symptoms and Risk of Amnestic Mild Cognitive Impairment.
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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: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: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:BACKGROUND:We 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). METHODS:We 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. RESULTS:In 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. CONCLUSIONS:Rates 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: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:BACKGROUND:Although amyloid-? (A?) and microstructural brain changes are both effective biomarkers of Alzheimer's disease, their independent or synergistic effects on cognitive decline are unclear. OBJECTIVE:To examine associations of A? and brain microstructure with cognitive decline in amnestic mild cognitive impairment and dementia. METHODS:Restriction spectrum imaging, cerebrospinal fluid A?, 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 A? with regional and whole-brain microstructure, and assessed whether microstructure mediates effects of A? on cognitive decline. RESULTS:Lower 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 A? or whole-brain microstructure. Correlations between microstructure and cognition were present for both amyloid-positive and amyloid-negative individuals. A? correlated with whole-brain, rather than regional, ND and IF. CONCLUSION:A? 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: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:Mild cognitive impairment (MCI) is widely regarded as an intermediate stage between typical aging and dementia, with nearly 50% of patients with amnestic MCI (aMCI) converting to Alzheimer's dementia (AD) within 30?months of follow-up (Fischer et al., 2007). The growing literature using resting-state functional magnetic resonance imaging reveals both increased and decreased connectivity in individuals with MCI and connectivity loss between the anterior and posterior components of the default mode network (DMN) throughout the course of the disease progression (Hillary et al., 2015; Sheline & Raichle, 2013; Tijms et al., 2013). In this paper, we use dynamic connectivity modeling and graph theory to identify unique brain "states," or temporal patterns of connectivity across distributed networks, to distinguish individuals with aMCI from healthy older adults (HOAs). We enrolled 44 individuals diagnosed with aMCI and 33 HOAs of comparable age and education. Our results indicated that individuals with aMCI spent significantly more time in one state in particular, whereas neural network analysis in the HOA sample revealed approximately equivalent representation across four distinct states. Among individuals with aMCI, spending a higher proportion of time in the dominant state relative to a state where participants exhibited high cost (a measure combining connectivity and distance), predicted better language performance and less perseveration. This is the first report to examine neural network dynamics in individuals with aMCI.
Project description:ABSTRACTObjective:There is increasing evidence of an association between depressive symptoms and mild cognitive impairment (MCI) in cross-sectional studies, but the longitudinal association between depressive symptoms and risk of MCI onset is less clear. The authors investigated whether baseline symptom severity of depression was predictive of time to onset of symptoms of MCI.MethodThese analyses included 300 participants from the BIOCARD study, a cohort of individuals who were cognitively normal at baseline (mean age = 57.4 years) and followed for up to 20 years (mean follow-up = 2.5 years). Depression symptom severity was measured using the Hamilton Depression Scale (HAM-D). The authors assessed the association between dichotomous and continuous HAM-D and time to onset of MCI within 7 years versus after 7 years from baseline (reflecting the mean time from baseline to onset of clinical symptoms in the cohort) using Cox regression models adjusted for gender, age, and education.ResultsAt baseline, subjects had a mean HAM-D score of 2.2 (SD = 2.8). Higher baseline HAM-D scores were associated with an increased risk of progression from normal cognition to clinical symptom onset ≤ 7 years from baseline (p = 0.043), but not with progression > 7 years from baseline (p = 0.194). These findings remained significant after adjustment for baseline cognition.ConclusionsThese results suggest that low levels of depressive symptoms may be predictive of clinical symptom onset within approximately 7 years among cognitively normal individuals and may be useful in identifying persons at risk for MCI due to Alzheimer's disease.
Project description:Background The association of depressive symptoms with health status in peripheral artery disease (PAD) is understudied. No reports of differential impact on women have been described. Methods and Results The PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Artery Disease Investigating Trajectories) registry enrolled 1243 patients from vascular specialty clinics with new or worsening PAD symptoms. Depressive symptoms were assessed at baseline and 3 months using the 8-Item Patient Health Questionnaire (score ≥10 indicating clinically relevant depressive symptoms). Disease-specific and generic health status were measured by Peripheral Artery Questionnaire and EQ-5D Visual Analogue Scale at baseline and 3, 6, and 12 months. An adjusted general linear model for repeated measures was constructed for baseline and 3-, 6-, and 12-month health status outcomes by depressive symptoms at baseline. Differences by sex were tested with interaction effects. The mean age was 67.6±9.4 years with 38% (n=470) women. More women than men (21.1% versus 12.9%; P<0.001) presented with severe depressive symptoms. In the adjusted model, patients with depressive symptoms had worse health status at each time point (all P<0.0001). Results were similar for EQ-5D Visual Analogue Scale scores. The magnitude in 1-year change in health status scores did not differ by sex. Depressive symptoms explained 19% of the association between sex differences in 1-year Peripheral Artery Questionnaire summary scores. Conclusions Women with PAD have a high burden of depressive symptoms. Depressive symptoms were associated with a strikingly worse disease-specific health status recovery path over the year following PAD diagnosis in men and women. Developing and testing interventions to address depressive symptoms in PAD are urgently needed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01419080.
Project description:Changes in white matter (WM) microstructure may relate to the pathophysiology of cognitive impairment. Whether WM microstructure differs in two common pre-dementia subtypes, vascular mild cognitive impairment (VaMCI) and amnestic mild cognitive impairment (aMCI), is largely unknown. This study included 28 VaMCI (12 men, age: 46 ~ 77 years) and 34 aMCI patients (14 men, age: 51 ~ 79 years). All patients underwent a battery of neuropsychological tests and structural and diffusion magnetic resonance imaging (MRI) scanning. WM microstructure was quantified using diffusion MRI parameters: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). These parameters were compared between the two patient groups using tract-based spatial statistics (TBSS) after controlling for age, gender, and education. No significant differences in FA/MD/AxD/RD were observed between the VaMCI and aMCI groups, which suggests a similar pattern of WM microstructure in the early stage of cognitive impairment for different dementia types. However, the two groups exhibited significant differences in the relationship between FA and the Auditory Verbal Learning Test (AVLT), which were primarily located around the corona radiate and corpus callosum. Specifically, there were significant positive correlations (R = 0.64, P < 0.001) between the FA and AVLT in the VaMCI group, but the opposite trend was observed in the aMCI group (R = -0.34, P = 0.047). The differential relationship between WM and memory between VaMCI and aMCI indicates an independent neuropathology for specific memory deficits in different types of dementia.
