Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Late-life depression and increased risk of dementia: a longitudinal cohort study.

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.

Resting state connectivity within the basal ganglia and gait speed in older adults with cerebral small vessel disease and locomotor risk factors.

BACKGROUND AND AIM: The basal ganglia are critical for planned locomotion, but their role in age-related gait slowing is not well known. Spontaneous regional co-activation of brain activity at rest, known as resting state connectivity, is emerging as a biomarker of functional neural specialization of varying human processes, including gait. We hypothesized that greater connectivity amongst regions of the basal ganglia would be associated with faster gait speed in the elderly. We further investigated whether this association was similar in strength to that of other risk factors for gait slowing, specifically white matter hyperintensities (WMH). METHODS: A cohort of 269 adults (79-90 years, 146 females, 164 White) were assessed for gait speed (m/sec) via stopwatch; brain activation during resting state functional magnetic resonance imaging, WMH, and gray matter volume (GMV) normalized by intracranial volume via 3T neuroimaging; and risk factors of poorer locomotion via clinical exams (body mass index (BMI), muscle strength, vision, musculoskeletal pain, cardiometabolic conditions, depressive symptoms, and cognitive function). To understand whether basal ganglia connectivity shows distinct clusters of connectivity, we conducted a k-means clustering analysis of regional co-activation among the substantia nigra, nucleus accumbens, subthalamic nucleus, putamen, pallidum, and caudate. We conducted two multivariable linear regression models: (1) with gait speed as the dependent variable and connectivity, demographics, WMH, GMV, and locomotor risk factors as independent variables and (2) with basal ganglia connectivity as the dependent variable and demographics, WMH, GMV, and locomotor risk factors as independent variables. RESULTS: We identified two clusters of basal ganglia connectivity: high and low without a distinct spatial distribution allowing us to compute an average connectivity index of the entire basal ganglia regional connectivity (representing a continuous measure). Lower connectivity was associated with slower gait, independent of other locomotor risk factors, including WMH; the coefficient of this association was similar to those of other locomotor risk factors. Lower connectivity was significantly associated with lower BMI and greater WMH. CONCLUSIONS: Lower resting state basal ganglia connectivity is associated with slower gait speed. Its contribution appears comparable to WMH and other locomotor risk factors. Future studies should assess whether promoting higher basal ganglia connectivity in older adults may reduce age-related gait slowing.

An improved algorithm of white matter hyperintensity detection in elderly adults.

Automated segmentation of the aging brain raises significant challenges because of the prevalence, extent, and heterogeneity of white matter hyperintensities. White matter hyperintensities can be frequently identified in magnetic resonance imaging (MRI) scans of older individuals and among those who have Alzheimer's disease. We propose OASIS-AD, a method for automatic segmentation of white matter hyperintensities in older adults using structural brain MRIs. OASIS-AD is an approach evolved from OASIS, which was developed for automatic lesion segmentation in multiple sclerosis. OASIS-AD is a major refinement of OASIS that takes into account the specific challenges raised by white matter hyperintensities in Alzheimer's disease. In particular, OASIS-AD combines three processing steps: 1) using an eroding procedure on the skull stripped mask; 2) adding a nearest neighbor feature construction approach; and 3) applying a Gaussian filter to refine segmentation results, creating a novel process for WMH detection in aging population. We show that OASIS-AD performs better than existing automatic white matter hyperintensity segmentation approaches.

When worry may be good for you: Worry severity and limbic-prefrontal functional connectivity in late-life generalized anxiety disorder.

BACKGROUND: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. METHODS: We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. RESULTS: Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LIMITATIONS: Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. CONCLUSIONS: This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.

Depressive symptoms and cerebral microvascular disease in adults with Type 1 diabetes mellitus.

AIM: To assess the prevalence of, and risk factors for, depressive symptoms, comparing a sample of middle-aged adults with and without juvenile-onset Type 1 diabetes mellitus, and to determine if depressive symptoms were associated with white matter hyperintensity volume among those with Type 1 diabetes. METHODS: Depressive symptoms and white matter hyperintensities were compared between adults (age range 30-65 years) with juvenile-onset Type 1 diabetes (n=130) and adults without Type 1 diabetes (n=133). The association of Type 1 diabetes with depression was computed before and after adjustment for white matter hyperintensities. Among the Type 1 diabetes group, the primary associations of interest were between depressive symptoms (Beck Depression Inventory score ≥10) and white matter hyperintensities (n=71), hyperglycaemia and physical activity. Associations between depressive symptoms and diabetes-related complications, cognitive impairment, smoking and self-reported disability were examined. Analyses were controlled for education, sex, age and antidepressant use. RESULTS: Depressive symptoms were more prevalent among those with vs those without Type 1 diabetes (28% vs 3%; P<0.001). White matter hyperintensities explained 40% of the association of Type 1 diabetes with depressive symptoms, while Type 1 diabetes had a direct effect of 68% on depressive symptoms. Among those with Type 1 diabetes, depressive symptoms were related to white matter hyperintensity volume, a 16-year average HbA1c ≥58 mmol/mol (7.5%), and lower physical activity levels. Associations with other characteristics were not significant. CONCLUSION: These findings suggest a cerebrovascular origin for depressive symptoms in adults with Type 1 diabetes, perhaps triggered by hyperglycaemia. Future longitudinal studies should investigate whether targeting hyperglycaemia and physical inactivity alleviates depressive symptoms, possibly by slowing the development of cerebral microvascular disease, in people with Type 1 diabetes.

In the grip of worry: cerebral blood flow changes during worry induction and reappraisal in late-life generalized anxiety disorder.

This corrects the article DOI: 10.1038/tp.2017.180.

In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T.

BACKGROUND AND PURPOSE: Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease-Alzheimer disease risk factors. MATERIALS AND METHODS: Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations. RESULTS: Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13-1.62). APOE4 presence was associated with a greater tortuosity ratio (ρ = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant. CONCLUSIONS: Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.

In the grip of worry: cerebral blood flow changes during worry induction and reappraisal in late-life generalized anxiety disorder.

Severe worry includes a complex blend of maladaptive affective and cognitive processes. Contrary to other forms of anxiety, there is no consensus in the field regarding the neural basis of worry. To date, no study has looked at neural patterns associated specifically with in-scanner induction and reappraisal of worry. In this study, we attempt to describe distinct components of the 'neural phenomenology' of worry: induction, maintenance, severity and reappraisal, by using a personalized, in-scanner worry script. Twenty older, non-anxious participants and twenty late-life generalized anxiety disorder (GAD) participants were included. Whole-brain axial pseudo-continuous arterial spin-labeling scans were collected. We used a voxel-wise two-way ANOVA to test the group-by-block interaction. Worry induction was associated with greater cerebral blood flow (CBF) in the visual cortex, thalamus, caudate and medial frontal cortex compared with the rest. Reappraisal was associated with greater CBF in similar regions, whereas the orbital frontal gyrus showed lower CBF relative to rest. Relative to non-anxious participants, GAD had greater CBF in multiple regions during worry induction (visual and parietal cortex, middle and superior frontal) and lower CBF during reappraisal in the supplemental motor area, middle cingulate gyrus, insula and putamen. Except for the thalamus, there was no change in CBF throughout the five blocks of worry induction and reappraisal. Severe worry is distinctly associated with increased CBF in several neocortical regulatory regions. We present new data supporting the view of worry as a complex process, engaging multiple regions in the initiation, maintenance and reappraisal of worry.

Association between change in brain gray matter volume, cognition, and depression severity: Pre- and post- antidepressant pharmacotherapy for late-life depression.

Late-life depression (LLD) is associated with cognitive impairments and reduced gray matter volume (GMV); however the mechanisms underlying this association are not well understood. The goal of this study was to characterize changes in depression severity, cognitive function, and brain structure associated with pharmacologic antidepressant treatment for LLD. We administered a detailed neurocognitive battery and conducted structural magnetic resonance imaging (MRI) on 26 individuals with LLD, pre-/post-a 12-week treatment trial with venlafaxine. After calculating changes in cognitive performance, GMV, and depression severity, we calculated Pearson's correlations, performed permutation testing, and false discovery rate correction. We found that loss of GMV over 12 weeks in the superior orbital frontal gyrus was associated with less improvement in depression severity and that increased GMV in the same was associated with greater improvement in depression severity. We detected no associations between changes in cognitive performance and improvements in either depressive symptoms or changes in GMV.

Intrinsic functional connectivity in late-life depression: trajectories over the course of pharmacotherapy in remitters and non-remitters.

Previous studies in late-life depression (LLD) have found that patients have altered intrinsic functional connectivity in the dorsal default mode network (DMN) and executive control network (ECN). We aimed to detect connectivity differences across a treatment trial among LLD patients as a function of remission status. LLD patients (N=37) were enrolled into a 12-week trial of venlafaxine and underwent five functional magnetic resonance imaging resting state scans during treatment. Patients had no history of drug abuse, psychosis, dementia/neurodegenerative diseases or medical conditions with known effects on mood. We investigated whether there were differences in three networks: DMN, ECN and anterior salience network connectivity, as well as a whole brain centrality measure (eigenvector centrality). We found that remitters showed increases in ECN connectivity in the right precentral gyrus and decreases in DMN connectivity in the right inferior frontal gyrus and supramarginal gyrus. The ECN and DMN had regions (middle temporal gyrus and bilateral middle/inferior temporal/fusiform gyrus, respectively) that showed reversed effects (decreased ECN and increased DMN, respectively). Early changes in functional connectivity can occur after initial medication exposure. This study offers new data, indicating that functional connectivity changes differ depending on treatment response and can occur shortly after exposure to antidepressant medication.

Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide.

BACKGROUND: Alongside impulsive suicide attempts, clinicians encounter highly premeditated suicidal acts, particularly in older adults. We have previously found that in contrast to the more impulsive suicide attempters' inability to delay gratification, serious and highly planned suicide attempts were associated with greater willingness to wait for larger rewards. This study examined neural underpinnings of intertemporal preference in suicide attempters. We expected that impulsivity and suicide attempts, particularly poorly planned ones, would predict altered paralimbic subjective value representations. We also examined lateral prefrontal and paralimbic correlates of premeditation in suicidal behavior. METHOD: A total of 48 participants aged 46-90 years underwent extensive clinical and cognitive characterization and completed the delay discounting task in the scanner: 26 individuals with major depression (13 with and 13 without history of suicide attempts) and 22 healthy controls. RESULTS: More impulsive individuals displayed greater activation in the precuneus/posterior cingulate cortex (PCC) to value difference favoring the delayed option. Suicide attempts, particularly better-planned ones, were associated with deactivation of the lateral prefrontal cortex (lPFC) in response to value difference favoring the immediate option. Findings were robust to medication exposure, depression severity and possible brain damage from suicide attempts, among other confounders. Finally, in suicide attempters longer reward delays were associated with diminished parahippocampal responses. CONCLUSIONS: Impulsivity was associated with an altered paralimbic (precuneus/PCC) encoding of value difference during intertemporal choice. By contrast, better-planned suicidal acts were associated with altered lPFC representations of value difference. The study provides preliminary evidence of impaired decision processes in both impulsive and premeditated suicidal behavior.

Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities.

The amyloid imaging agent, Pittsburgh Compound-B, binds with high affinity to ß-amyloid (Aß) in the brain, and it is well established that PiB also shows non-specific retention in white matter (WM). However, little is known about retention of PiB in areas of white matter hyperintensities (WMH), abnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to both cognitive dysfunction and Aß deposition. The goal of the present study was to explore PiB retention in both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all subjects, regardless of WMH burden or size. (2) Subject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of subjects with high WMH compared to subjects with low WMH. Additionally, in subjects with high WMH, there was significantly lower PiB retention in subject-specific maps of WMH compared to NAWM, which was not observed in subjects with low WMH, likely because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights about the molecular basis of the non-specific retention of amyloid tracers in white matter.

Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression.

Cognitive impairment is highly prevalent among individuals with late-life depression (LLD) and tends to persist even after successful treatment. The biological mechanisms underlying cognitive impairment in LLD are complex and likely involve abnormalities in multiple pathways, or 'cascades,' reflected in specific biomarkers. Our aim was to evaluate peripheral (blood-based) evidence for biological pathways associated with cognitive impairment in older adults with LLD. To this end, we used a data-driven comprehensive proteomic analysis (multiplex immunoassay including 242 proteins), along with measures of structural brain abnormalities (gray matter atrophy and white matter hyperintensity volume via magnetic resonance imaging), and brain amyloid-ß (Aß) deposition (PiB-positron emission tomography). We analyzed data from 80 older adults with remitted major depression (36 with mild cognitive impairment (LLD+MCI) and 44 with normal cognitive (LLD+NC)) function. LLD+MCI was associated with differential expression of 24 proteins (P<0.05 and q-value <0.30) related mainly to the regulation of immune-inflammatory activity, intracellular signaling, cell survival and protein and lipid homeostasis. Individuals with LLD+MCI also showed greater white matter hyperintensity burden compared with LLD+NC (P=0.015). We observed no differences in gray matter volume or brain Aß deposition between groups. Machine learning analysis showed that a group of three proteins (Apo AI, IL-12 and stem cell factor) yielded accuracy of 81.3%, sensitivity of 75% and specificity of 86.4% in discriminating participants with MCI from those with NC function (with an averaged cross-validation accuracy of 76.3%, sensitivity of 69.4% and specificity of 81.8% with nested cross-validation considering the model selection bias). Cognitive impairment in LLD seems to be related to greater cerebrovascular disease along with abnormalities in immune-inflammatory control, cell survival, intracellular signaling, protein and lipid homeostasis, and clotting processes. These results suggest that individuals with LLD and cognitive impairment may be more vulnerable to accelerated brain aging and shed light on possible mediators of their elevated risk for progression to dementia.

Corticostriatothalamic reward prediction error signals and executive control in late-life depression.

BACKGROUND: Altered corticostriatothalamic encoding of reinforcement is a core feature of depression. Here we examine reinforcement learning in late-life depression in the theoretical framework of the vascular depression hypothesis. This hypothesis attributes the co-occurrence of late-life depression and poor executive control to prefrontal/cingulate disconnection by vascular lesions. METHOD: Our fMRI study compared 31 patients aged ⩾60 years with major depression to 16 controls. Using a computational model, we estimated neural and behavioral responses to reinforcement in an uncertain, changing environment (probabilistic reversal learning). RESULTS: Poor executive control and depression each explained distinct variance in corticostriatothalamic response to unexpected rewards. Depression, but not poor executive control, predicted disrupted functional connectivity between the striatum and prefrontal cortex. White-matter hyperintensities predicted diminished corticostriatothalamic responses to reinforcement, but did not mediate effects of depression or executive control. In two independent samples, poor executive control predicted a failure to persist with rewarded actions, an effect distinct from depressive oversensitivity to punishment. The findings were unchanged in a subsample of participants with vascular disease. Results were robust to effects of confounders including psychiatric comorbidities, physical illness, depressive severity, and psychotropic exposure. CONCLUSIONS: Contrary to the predictions of the vascular depression hypothesis, altered encoding of rewards in late-life depression is dissociable from impaired contingency learning associated with poor executive control. Functional connectivity and behavioral analyses point to a disruption of ascending mesostriatocortical reward signals in late-life depression and a failure of cortical contingency encoding in elderly with poor executive control.

Pattern recognition analysis of anterior cingulate cortex blood flow to classify depression polarity.

Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode--18 with bipolar disorder type I, 18 with recurrent unipolar depression--we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity).

The vascular depression hypothesis: mechanisms linking vascular disease with depression.

The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes.

Generalized tensor-based morphometry of HIV/AIDS using multivariate statistics on deformation tensors.

This paper investigates the performance of a new multivariate method for tensor-based morphometry (TBM). Statistics on Riemannian manifolds are developed that exploit the full information in deformation tensor fields. In TBM, multiple brain images are warped to a common neuroanatomical template via 3-D nonlinear registration; the resulting deformation fields are analyzed statistically to identify group differences in anatomy. Rather than study the Jacobian determinant (volume expansion factor) of these deformations, as is common, we retain the full deformation tensors and apply a manifold version of Hotelling's $T(2) test to them, in a Log-Euclidean domain. In 2-D and 3-D magnetic resonance imaging (MRI) data from 26 HIV/AIDS patients and 14 matched healthy subjects, we compared multivariate tensor analysis versus univariate tests of simpler tensor-derived indices: the Jacobian determinant, the trace, geodesic anisotropy, and eigenvalues of the deformation tensor, and the angle of rotation of its eigenvectors. We detected consistent, but more extensive patterns of structural abnormalities, with multivariate tests on the full tensor manifold. Their improved power was established by analyzing cumulative p-value plots using false discovery rate (FDR) methods, appropriately controlling for false positives. This increased detection sensitivity may empower drug trials and large-scale studies of disease that use tensor-based morphometry.

Acceleration of cerebral ventricular expansion in the Cardiovascular Health Study.

Interactions between prevalent late-life medical conditions and expansion of the cerebral ventricles are not well understood. Thirty elderly subjects received three magnetic resonance (MR) scans each, in 1997-1999, 2002-2004, and 2003-2005. A linear expansion model of MR-measured lateral ventricle volume was estimated for each subject by fitting a line to a plot of their 1997-1999 and 2002-2004 volumes as a function of time. Acceleration in ventricular expansion was defined as the deviation between the 2003-2005 volumes measured from MR and the 2003-2005 volumes predicted by the linear expansion model. Ventricular acceleration was analyzed in a multivariate model with age, race, history of heart disease, diabetes, and hypertension as fixed effects. Ventricular acceleration was significantly higher in non-whites, diabetics, and those without heart disease (p<0.05). Ventricular acceleration was higher in subjects with a history of hypertension, but the difference was not statistically significant (p=0.08). Acceleration of ventricular expansion in the elderly may be related to demographic and cardiovascular factors.

The relation of White Matter Hyperintensities to implicit learning in healthy older adults.

OBJECTIVE: This study examined whether MRI evidence of cerebrovascular disease in the form of white matter hyperintensities (WMH) was associated with decreased implicit sequence learning performance in a high-functioning group of normal elderly volunteers. METHOD: One hundred and eight community-dwelling elderly individuals received an MRI and performed an implicit sequence learning task, the serial reaction time (SRT) task. RESULTS: Hyperintensities present in the white matter were associated with a decreased learning effect. This association was found with both deep white matter and periventricular changes. Other factors affecting SRT performance (i.e., baseline reaction time and switch-cost) were not significantly related to the presence of WMH. CONCLUSIONS: The results indicate that in addition to previously identified generalized cognitive deficits, WMH are also associated with a specific decrease in the implicit learning of sequences.