Clinical and radiological characteristics of early versus late mild cognitive impairment in patients with comorbid depressive disorder.

OBJECTIVE: The classification of mild cognitive impairment (MCI) continues to be debated though it has recently been subtyped into late (LMCI) versus early (EMCI) stages. Older adults presenting with both a depressive disorder (DEP) and cognitive impairment (CI) represent a unique, understudied population. Our aim was to examine baseline characteristics of DEP-CI patients in the DOTCODE trial, a randomized controlled trial of open antidepressant treatment for 16 weeks followed by add-on donepezil or placebo for 62 weeks. METHODS/DESIGN: Key inclusion criteria were diagnosis of major depression or dysthymic disorder with Hamilton Depression Rating Scale (HAM-D) score >14, and cognitive impairment defined by MMSE score ≥21 and impaired performance on the WMS-R Logical Memory II test. Patients were classified as EMCI or LMCI based on the 1.5 SD cutoff on tests of verbal memory, and compared on baseline clinical, neuropsychological, and anatomical characteristics. RESULTS: Seventy-nine DEP-CI patients were recruited of whom 39 met criteria for EMCI and 40 for LMCI. The mean age was 68.9, and mean HAM-D was 23.0. Late mild cognitive impairment patients had significantly worse ADAS-Cog (P < .001), MMSE (P = .004), Block Design (P = .024), Visual Rep II (P = .006), CFL Animal (P = .006), UPSIT (P = .051), as well as smaller right hippocampal volume (P = .037) compared to EMCI patients. MRI indices of cerebrovascular disease did not differ between EMCI and LMCI patients. CONCLUSIONS: Cognitive and neuronal loss markers differed between EMCI and LMCI among patients with DEP-CI, with LMCI being more likely to have the clinical and neuronal loss markers known to be associated with Alzheimer's disease.

Vascular depression: overrepresented among African Americans?

OBJECTIVE: Our primary aim was to compare the rate of vascular depression among a clinical sample of African American and Caucasian depressed older adults. Secondary aims included characterizing the clinical and neuropsychological profile of vascular depression and comparing antidepressant response rates between patients with vascular and nonvascular depression. METHODS: This was a two-site, multi-ethnic, open 8-week trial of antidepressant medication in older adults with depression. Men and women 50 years or older meeting DSM-IV criteria for nonpsychotic unipolar depression participated in this trial. Each participant underwent a comprehensive psychiatric and neuropsychological evaluation and a brain MRI, which were performed at baseline. RESULTS: Forty-six patients met inclusion and exclusion criteria. Forty-two of those patients received an MRI at baseline. Sixteen patients met criteria for vascular depression. Patients with vascular depression were significantly more likely to be African American and have a higher likelihood of being female, a higher rate of hypertension and psychomotor retardation, a lower rate of family history of affective illness, and frontal systems dysfunction on neuropsychological testing. The difference in response rates between patients with vascular and nonvascular depression did not reach statistical significance. CONCLUSIONS: This is the first study to document high rates of vascular depression in a clinical sample of African Americans and Caucasians. Our findings suggest that vascular depression may be overrepresented among African Americans, which is consistent with the high rates of cardiovascular disease, hypertension, and stroke in this population.

The external validity of MRI-defined vascular depression.

OBJECTIVE: Multiple diagnostic criteria have been used to define vascular depression (VD). As a result, there are discrepancies in the clinical characteristics that have been established for the illness. The aim of this study was twofold. First, we used empirically established diagnostic criteria to determine the clinical characteristics of magnetic resonance imaging (MRI)-defined VD. Second, we assessed the agreement between a quantitative and qualitative method for identifying the illness. METHOD: We examined the baseline clinical and neuropsychological profile of 38 patients from a larger, double-blind, randomized, 12-week clinical trial comparing nortriptyline with sertraline in depressed older adults. Ten patients met quantitative criteria for MRI-defined VD based on the highest quartile of deep white matter hyperintensity (DWMH) volume. Fourteen patients met qualitative criteria for MRI-defined VD based on a DWMH score of 2 or higher on the Fazekas' modified Coffey rating scale. RESULTS: Age, gender, cumulative illness rating scale-geriatric (CIRS-G) score, two measures of psychomotor retardation [the psychomotor retardation item of the Hamilton Rating Scale for Depression (HRSD) as well as performance on the Purdue Pegboard], and performance on the Stroop Color/Word test (a measure of the response inhibition component of executive functioning) were significantly different between those with VD and non-VD. CONCLUSIONS: Patients with VD have a distinct clinical and neuropsychological profile that is mostly consistent across different methods for identifying the illness. These findings support the notion that MRI-defined VD represents a unique and valid subtype of late-life depression.

MRI-defined vascular depression: a review of the construct.

OBJECTIVE: To review the construct of MRI-defined vascular depression and to examine the substantive and methodological issues that bear on its validity as a distinct subtype of depression in late life. DESIGN: Literature review. RESULTS: We identified three areas that are critical to establishing the validity of MRI-defined vascular depression: (1) understanding and delineating the relationship between MRI hyperintensities, executive dysfunction, and antidepressant treatment outcome; (2) understanding the relationship between, and establishing the validity of, qualitative and quantitative approaches to the measurement of MRI hyperintensities (the primary feature of the proposed subtype); (3) establishing the clinical presentation and course of the subtype in the context of other late-life disorders. CONCLUSIONS: Despite considerable data supporting the validity of MRI-defined vascular depression, there are a number of critical issues that remain, including establishing a causal relationship between cerebrovascular disease and late-life depression, establishing consistent diagnostic criteria, determining the importance of lesion type and location, and understanding the course of the disorder.

Quantitative approaches for assessment of white matter hyperintensities in elderly populations.

White matter hyperintensities (WMH) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI), including fluid attenuated inverse recovery sequences. Total and regional WMH burden (i.e., volume or severity) has been associated with myriad cognitive, neurological, and psychiatric conditions among older adults. In the current report, we illustrate two approaches to quantify periventricular, deep, and total WMH and examine their reliability and criterion validity among 28 elderly patients enrolled in a depression treatment trial. The first approach, an operator-driven quantitative approach, involves visual inspection of individual MRI scans and manual labeling using a three-step series of procedures. The second approach, a fully automated quantitative approach, uses a processing stream that involves image segmentation, voxel intensity thresholding, and seed growing to label WMH and calculate their volume automatically. There was good agreement in WMH quantification between the two approaches (Cronbach's alpha values from 0.835 to 0.968). Further, severity of WMH was significantly associated with worse depression and increased age, and these associations did not differ significantly between the two quantification approaches. We provide evidence for good reliability and criterion validity for two approaches for WMH volume determination. The operator-driven approach may be better suited for smaller studies with highly trained raters, whereas the fully automated quantitative approach may be more appropriate for larger, high-throughput studies.

Vascular depression for radiology: A review of the construct, methodology, and diagnosis.

Vascular depression (VD) as defined by magnetic resonance imaging (MRI) has been proposed as a unique subtype of late-life depression. The VD hypothesis posits that cerebrovascular disease, as characterized by the presence of MRI-defined white matter hyperintensities, contributes to and increases the risk for depression in older adults. VD is also accompanied by cognitive impairment and poor antidepressant treatment response. The VD diagnosis relies on MRI findings and yet this clinical entity is largely unfamiliar to neuroradiologists and is rarely, if ever, discussed in radiology journals. The primary purpose of this review is to introduce the MRI-defined VD construct to the neuroradiology community. Case reports are highlighted in order to illustrate the profile of VD in terms of radiological, clinical, and neuropsychological findings. A secondary purpose is to elucidate and elaborate on the measurement of cerebrovascular disease through visual rating scales and semi- and fully-automated volumetric methods. These methods are crucial for determining whether lesion burden or lesion severity is the dominant pathological contributor to VD. Additionally, these rating methods have implications for the growing field of computer assisted diagnosis. Since VD has been found to have a profile that is distinct from other types of late-life depression, neuroradiologists, in conjunction with psychiatrists and psychologists, should consider VD in diagnosis and treatment planning.

Horner's syndrome: clinical and radiographic evaluation.

Horner's syndrome (HS) occurs when there is interruption of the oculosympathetic pathway (OSP). This article reviews the anatomy of the OSP and clinical findings associated with lesions located at various positions along this pathway. The imaging findings of lesions associated with HS at various levels of the OSP, classified as preganglionic HS (first- and second-order neuron HS) or postganglionic HS (third-order neuron HS), are demonstrated.

MRI signal hyperintensities and failure to remit following antidepressant treatment.

BACKGROUND: MRI signal hyperintensities predict poor remission to antidepressant treatment. Previous studies using volumetrics in outpatient samples have relied on total lesion volume. The purpose of this study was to test whether remission from geriatric depression depends on lesion volume by region of interest (ROI). METHOD: Thirty-eight patients received baseline MRIs as part of a larger 12-week, randomized clinical trial comparing sertraline and nortriptyline in the treatment of late-life depression. MRIcro was used to quantify MRI-hyperintensity volume into total hyperintensity, deep white matter hyperintensity (DWMH), and periventricular hyperintensity (PVH) volumes. High versus low total, DWMH, and PVH volumes were defined based on the highest quartile of their respective distributions. Remission from depression was defined as a 24-item Hamilton Rating Scale for Depression score ≤ 7 for two consecutive weeks. RESULTS: Patients classified as having high DWMH were 7.14 times more likely not to remit following antidepressant treatment compared to patients classified as having low DWMH (p=0.02). Similar odds ratios were obtained for PVH (OR=4.17, p=0.16) and total volumes (OR=5.00, p=0.05). Importantly, adjusting for age did not change the magnitude of these effects. LIMITATIONS: A small and predominantly White sample. CONCLUSIONS: This is the first study to test whether remission from geriatric depression depends on lesion volume by ROI in an outpatient sample. The pattern of remission rates and odds ratios was similar when patients were classified as having high DWMH, PVH or total volume suggesting that lesion location may not be critical.