David M. Lefkowitz

Psychometric Limitations of the Mini-Mental State Examination Among Nondemented Older Adults: An Evaluation of Neurocognitive and Magnetic Resonance Imaging Correlates

Background/Study Context: Although many of the Mini-Mental State Examinations (MMSE) limitations are well accepted among geriatricians, neuropsychologists, and other interested clinicians and researchers, its continued use in psychometrically unsound ways suggests that additional investigation and dissemination of information are sorely needed. The authors aimed to describe the reliability and validity of the MMSE as a measure of cognitive function among healthy older adults. Methods: The authors examined MMSE performance in 124 stroke- and dementia-free, community-dwelling older adults (65% male; mean age = 66.5 years). All participants were administered an extensive neuropsychological battery composed of measures of attention, executive function, memory, and visuospatial function. A subset of 99 participants also underwent magnetic resonance imaging (MRI). MMSE test-retest reliability was examined among 65 participants who underwent repeat MMSE testing over an average interval of 83.2 days. Results: Spearman test-retest correlation for total MMSE scores was r S = .35 (p = .004), for Serial Sevens was r S = .40 (p = .001), and for Word Recall was r S = −.01 (p = .96). Total MMSE performance correlated significantly with a minority of neuropsychological tests and MRI-derived indices of white matter disease and brain atrophy. A subset of 17% of participants demonstrated inappropriate intrusion of MMSE Pentagon Copy during another test of visuospatial recall. Conclusions: Overall, MMSE scores exhibited ceiling effects, poor test-retest reliability, limited sensitivity to subtle brain abnormalities, and a high rate of intrusion elsewhere in the neuropsychological battery. Individual MMSE items demonstrated poor construct validity. These qualities illustrate the serious limitations of the MMSE in detecting individual differences in cognitive function among healthy older adults.

Reduced cerebral blood flow in older men with higher levels of blood pressure.

Objective To examine relations of blood pressure (BP) with single photon emission computed tomography (SPECT)-derived estimates of cerebral blood flow in older men and women. Methods Seventy-four stroke and dementia-free, community-dwelling older adults (ages 54–83 years; 68% men; 91% white) free of major medical, neurological, or psychiatric disease, engaged in clinical assessment of resting SBP and DBP, MRI rated for brain atrophy, and brain single photon emission computed tomography (SPECT) studies with computerized coding of cortical and select subcortical regions of interest. Results Given significant interactions of BP and sex with respect to multiple SPECT outcomes, sex-stratified multiple regression models were computed. Models were adjusted for age, fasting glucose levels, antihypertensive medication, BMI, and MRI ratings of brain atrophy. In men (n = 50), higher levels of SBP and/or DBP were associated significantly with lower estimates of cerebral perfusion in the right and left frontal, temporal, parietal, and occipital cortex, thalamus, head of caudate, and cingulate cortex accounting for up to 28% of the variance in these measures (P < 0.05). In women (n = 24), higher DBP was related marginally to higher levels of perfusion in the right temporal cortex (P = 0.05). Conclusion Higher resting SBP or DBP was associated with lower levels of cerebral perfusion in otherwise healthy older men, but not women, in the present sample. Reduced cerebral blood flow may play a pathogenic role in increasing risk for stroke, dementia, and/or cognitive decline, particularly among older men with high BP.

Relationship of cerebrospinal fluid glucose metabolites to MRI deep white matter hyperintensities and treatment resistance in bipolar disorder patients

OBJECTIVES Both diabetes mellitus and magnetic resonance image (MRI) deep white matter hyperintensities (WMHs) are more common in bipolar disorder (BD) patients than in matched controls. Deep-as opposed to periventricular--WMHs and diabetes are associated with treatment resistance and poorer outcome. This study investigated whether brain glucose metabolism by the polyol pathway--a pathway linked to nervous tissue disease in diabetes--is related to deep WMH volume and treatment resistance in BD patients. METHODS Volumes of fluid-attenuated inversion recovery WMHs were quantified and correlated with cerebrospinal fluid (CSF) concentrations of glucose metabolites in 20 nondiabetic patients with BD and nondiabetic comparison subjects with schizophrenia (n = 15) or transient neurologic symptoms (neurologic controls, n = 15). RESULTS BD patients, but not schizophrenic patients, had significantly greater volumes of deep but not periventricular WMHs compared to neurologic controls. BD subjects also had significantly greater CSF concentrations of sorbitol and fructose (the polyol pathway metabolites of glucose) compared to controls. Significant positive correlations between CSF metabolites and WMH volumes were found only in the BD group and were between deep WMH volumes and CSF sorbitol (rho = 0.487, p = 0.029) and fructose (rho = 0.474, p = 0.035). An index of treatment resistance correlated significantly with deep WMH volume (rho = 0.578, p = 0.008), sorbitol (rho = 0.542, p = 0.013), and fructose (rho = 0.692, p = 0.001) in BD subjects but not in other subjects. CONCLUSIONS This is the first reported evidence of relationships between abnormal brain glucose metabolism and both deep WMHs and treatment resistance in a group of BD patients. Further studies are necessary to determine the significance of these findings to BD pathophysiology.

Patterns of cranial, brain and sulcal CSF volumes in male and female deficit and nondeficit patients with schizophrenia

Recent evidence suggests that schizophrenia reflects a neurodegenerative process. The studies have not compared brain change patterns in male and female patients with schizophrenia or examined the relation of these patterns to patient subgroups defined by specific symptom domains. Maximum Total Brain Volume (TBVmax), total cranial (TCV), total brain (TBV), sulcal CSF (sCSF), and ventricular (VV) volumes were measured in 66 normal controls (32 females, 34 males), and 85 patients with schizophrenia (21 females, 64 males). Sixty-six patients were categorized as nondeficit and 19 as deficit patients. Patients had smaller TBV and larger VV than normal controls. Patients also showed significant excessive brain volume loss after, but not before, TBVmax was achieved compared with normal controls. Although male patients had larger brain volume loss compared with male normal controls than female patients had compared with female normal controls, there were no significant gender x diagnosis interactions. Male patients with the deficit syndrome, but not those without the deficit syndrome, had significantly larger ventricles than normal controls. There were no other significant deficit/nondeficit differences. The present study suggests that brain volume loss in schizophrenia occurs after TBVmax and that male and female patients and deficit and nondeficit patients with schizophrenia do not demonstrate any differences in the time course of their brain volume reductions.

Depressive symptoms are associated with subclinical cerebrovascular disease among healthy older women, not men.

BACKGROUND Associations among diagnosed unipolar depression, depressive symptoms, and cerebrovascular disease are well known. However, minimal research has investigated whether sex may modify such associations, despite known sex differences in depression and depressive symptoms. This study examined whether depressive symptoms were disproportionately related to subclinical cerebrovascular disease (SCD) in women versus men. METHODS One hundred one older adults (58% men; mean age = 67 years), free of major comorbidities, completed the Beck Depression Inventory and underwent magnetic resonance imaging (MRI). MRI scans were neuroradiologist rated for markers of SCD (periventricular and deep white matter hyperintensities, and number of silent infarcts) and brain atrophy (ventricular enlargement and sulcal widening). Two rank-sum outcome variables (SCD and brain atrophy) were then created. RESULTS On average, depressive symptoms were relatively low in magnitude (mean = 3.8, standard deviation = 3.6, range = 0-17). Multiple regression analyses, adjusted for age, sex, education, systolic blood pressure, fasting glucose, maximal oxygen consumption, body mass index, average weekly alcohol consumption, and Mini-Mental State Examination performance revealed sex to be a significant effect modifier of depressive symptoms in the prediction of SCD. Sex-stratified regression analyses indicated depressive symptoms, and SCD was strongly related among women but not men. Depressive symptoms were not related to brain atrophy, regardless of inclusion of sex as an effect modifier. CONCLUSIONS Depressive symptoms, even in a subclinical range, are significantly associated with an MRI-derived index of SCD among women, but not men, in the present sample of relatively healthy older adults.

Complex partial status epilepticus in a patient with dural metastases

We describe a 68-year-old man with invasive transitional cell carcinoma of the bladder metastatic to the dura who presented with complex partial status epilepticus (CPSE). To our knowledge, the association of CPSE and dural metastases has not been previously reported.

Interactive relations of blood pressure and age to subclinical cerebrovascular disease.

Objective: To examine interactive relations of blood pressure (BP) and age to MRI indices of subclinical cerebrovascular disease in middle-aged to older adults. Methods: One hundred and thirteen stroke-free and dementia-free, community-dwelling adults (ages 54–81 years; 65% men; 91% white) engaged in (1) clinical assessment of resting SBP and DBP; (2) MRI rated for periventricular white matter hyperintensities (WMH) and deep WMH silent brain infarction (SBI) and brain atrophy (i.e. ventricular enlargement and sulcal widening ). Principal components analysis of the MRI ratings yielded a two-component solution – (1) periventricular and deep WMH SBI; and (2) ventricular enlargement, sulcal widening. Results: Relations of SBP, DBP and pulse pressure (PP) (and their interactions with age) to each MRI component were examined in multiple regression analyses adjusted for age, sex, fasting plasma glucose and cholesterol, and antihypertensives. For component 1, results indicated significant interactions of SBP and PP with age (P < 0.05); higher levels of SBP and PP were associated with greater white matter disease and brain infarction at younger ages (⩽68 years). Significant interactions of SBP and DBP with age were also noted for component 2 (P < 0.05); higher levels of BP were associated with greater brain atrophy at younger ages (⩽63 years). Conclusion: Higher BP and PP are associated with greater subclinical cerebrovascular disease most prominently in the ‘young old’. Appropriate management of hypertension and arterial stiffening may be critical to the preservation of brain structure with ageing.

Cerebral blood flow and anxiety in older men: An analysis of resting anterior asymmetry and prefrontal regions

Asymmetric resting blood flow in prefrontal and hemispheric regions, assessed by single photon emission computed tomography (SPECT), was examined as a potential biological marker for enhanced trait and state anxiety in 30 older men (ages 55-81). Average and asymmetric perfusion in dorsolateral, medial, and orbital regions of the prefrontal lobes was also assessed. Results indicated a significant association between lower levels of resting dorsolateral blood flow and greater state anxiety responses to a series of stressful provocations (measured on a separate occasion). A significant curvilinear (U-shaped) relation between asymmetric dorsolateral perfusion and state anxiety was also identified; increased asymmetric blood flow favoring either the right or the left dorsolateral region related to higher levels of state anxiety. However, this association was attenuated by age and systolic blood pressure. Resting perfusion in the dorsolateral region may represent a more reliable biological marker for state anxiety than trait anxiety in older men.

Association of fasting glucose with subclinical cerebrovascular disease in older adults without Type 2 diabetes.

To examine how fasting glucose and glucose tolerance are related to magnetic resonance imaging‐assessed indicators of subclinical cerebrovascular disease and brain atrophy and their variation according to age, sex and education.