Cognitive-behavioral profiles of neurodegenerative dementias: beyond Alzheimer's disease.

The neurocognitive and behavioral profiles of vascular dementia and vascular cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia, and dementia syndromes associated with frontotemporal lobar degenerations are compared and contrasted with Alzheimer's dementia (AD). Vascular dementia/vascular cognitive impairment is characterized by better verbal memory performance, worse quantitative executive functioning, and prominent depressed mood. Dementia with Lewy bodies and Parkinson's disease with dementia are equally contrasted with AD by defective processing of visual information, better performance on executively supported verbal learning tasks, greater attentional variability, poorer qualitative executive functioning, and the presence of mood-congruent visual hallucinations. The frontal variant of frontotemporal lobar degeneration (frontotemporal dementia) differs from AD by better multimodal retention on learning tasks, different patterns of generative word fluency, defective qualitative executive functioning, and by markedly impairment of comportment. For temporal variants of frontotemporal lobar degenerations, progressive aphasia and semantic dementia, worse language performance relative to AD is typically characteristic.

Stability of CSF beta-amyloid(1-42) and tau levels by APOE genotype in Alzheimer patients.

BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42 )and tau differ between patients with Alzheimer's Disease (AD) and elderly normal controls. The effect of time and APOE genotype on these biomarkers continues to be elucidated. METHODS: We assessed CSF beta-amyloid(1-42) and tau in 20 mild-to-moderate AD patients, 11 APOE epsilon4+ and 9 APOE epsilon4-, over a mean time of 3.8 years (range 1-11.1 years). RESULTS: Over the period measured, CSF beta-amyloid(1-42) levels were lower in APOE epsilon4+ compared to APOE epsilon4- patients, and the levels decreased over time. Tau levels were stable over time and did not show an effect of APOE allele. CONCLUSIONS: While this is a limited clinical sample, the further decrease in CSF beta-amyloid(1-42 )(i.e., more abnormal) combined with the CSF tau stability over a mean period of almost 4 years suggests that beta-amyloid(1-42 )and tau maintain their potential usefulness as diagnostic biomarkers over time. These findings should be taken into account if CSF beta-amyloid(1-42) and tau are used as measures of treatment response.

Prevalence of echocardiographic left ventricular hypertrophy in persons with systemic hypertension, coronary artery disease, and peripheral arterial disease and in persons with systemic hypertension, coronary artery disease, and no peripheral arterial disease.

Echocardiographic left ventricular (LV) hypertrophy was present in 120 of 160 patients (75%) (mean age 72 +/- 8 years) with systemic hypertension, coronary artery disease, and peripheral arterial disease (PAD) and in 43 of 94 age- and gender-matched patients (46%) with systemic hypertension, coronary artery disease, and no PAD (p<0.001). Echocardiographic LV hypertrophy was present in 63 of 68 patients with PAD (93%) with ankle-brachial indexes (ABIs) of <0.60 and in 57 of 92 patients (62%) with ABIs of 0.60 to 0.89 (p<0.001).

Circadian preference and cognitive functioning among rehabilitation inpatients.

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n=28) and noncognitive (n=28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta2 .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e/g/. complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, and index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.

Effects of previous major depressive illness on cognition in Alzheimer disease patients.

OBJECTIVE: Major Depressive Disorder (MDD) may be a risk factor for subsequent development of irreversible dementia; however, the influence of a premorbid history of MDD on the clinical course of patients diagnosed with probable Alzheimer disease (AD) has not been fully explored. METHODS: Forty-three AD patients with mild-to-moderate cognitive impairment were screened for a life-long history of MDD with the Clinical Assessment of Depression in Dementia Scale. Twenty-two subjects had a history of MDD before onset of cognitive impairment, but none was suffering from an MDD episode at time of cognitive assessment. RESULTS: After controlling for age, education, duration of illness, gender, and medication status, subjects with a history of MDD had significantly lower scores, as a group, on cognitive performance tests, including the Mini-Mental State Exam, WAIS Full-Scale and Verbal Scale I.Q., and the Initiation/Perseveration subscale of the Mattis Dementia Rating Scale. These subjects also developed symptoms of dementia at a significantly earlier age than the subjects who had no premorbid history of MDD. CONCLUSIONS: Although previous studies have shown that late-onset MDD may increase risk for subsequent dementia, the current results suggest that premorbid MDD is associated with more severe cognitive deficits during the actual course of dementia.

Association of right ventricular dilatation with bilateral pulmonary embolism, pulmonary embolism in a main pulmonary artery and lobar, segmental and subsegmental pulmonary embolism in 190 patients with acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) may result in right ventricular (RV) pressure overload with a dilated RV which can be diagnosed by two-dimensional echocardiography. METHODS: A retrospective analysis was performed in 190 unselected patients who had acute PE documented by contrast-enhanced spiral computed tomographic scanning. The 190 patients included 104 women and 86 men, mean age 58 +/- 15 years. RESULTS: RV dilatation was present in 45 of 70 patients (64%) with bilateral PE, in 19 of 120 patients (16%) without bilateral PE, in 42 of 47 patients (89%) with main pulmonary artery embolism, in 34 of 84 patients (40%) with lobar PE, in 16 of 70 patients (23%) with segmental PE and in 6 of 36 patients (17%) with subsegmental PE; p < 0.001 comparing bilateral with no bilateral PE and main pulmonary artery embolism with no main pulmonary artery embolism, with lobar, segmental and subsegmental PE; p < 0.025 comparing lobar with segmental PE, and p < 0.02 comparing lobar with subsegmental PE. CONCLUSION: The prevalence of RV dilatation is highest in patients with main pulmonary artery embolism or bilateral pulmonary artery embolism; furthermore, the prevalence of RV dilatation is higher in patients with lobar PE than in patients with segmental or subsegmental PE.

Association of right ventricular dysfunction with in-hospital mortality in patients with acute pulmonary embolism and reduction in mortality in patients with right ventricular dysfunction by pulmonary embolectomy.

Twenty-one of 64 patients (33%) with pulmonary embolisms with right ventricular (RV) dilation and 6 of 126 patients (5%) with pulmonary embolisms without RV dilation died during hospitalization (p <0.001). In the 64 patients with RV dilation, in-hospital mortality occurred in 2 of 18 hemodynamically unstable patients (11%) who underwent pulmonary embolectomy, in 2 of 6 hemodynamically stable patients (33%) treated with thrombolytic therapy plus intravenous heparin, and in 17 of 40 hemodynamically stable patients (43%) treated with intravenous heparin (p <0.025 comparing pulmonary embolectomy with no pulmonary embolectomy).

Cerebrospinal fluid beta-amyloid1-42 and tau in control subjects at risk for Alzheimer's disease: the effect of APOE epsilon4 allele.

BACKGROUND: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau are linked with the known neuropathology of Alzheimer's disease (AD). Numerous lines of evidence have also suggested that individuals with at least one APOE epsilon4 allele on chromosome 19 are at increased risk of developing AD. We tested these CSF markers in groups of subjects with AD and healthy older control subjects, using the absence or presence of the APOE epsilon4 allele as a predictive variable in the search for possible prognostic biomarkers of AD. METHODS: We assessed the levels of beta-amyloid(1-42) and total tau in the CSF of 292 subjects (142 control subjects and 150 subjects with mild-to-moderate AD), who were research participants at the National Institute of Mental Health. The group of control subjects was enriched with a high percentage of subjects with a positive family history of AD. All subjects underwent extensive global cognitive testing. RESULTS: When divided according to the absence or presence of the APOE epsilon4 allele, the control subjects with at least one epsilon4 allele had significantly lower CSF beta-amyloid(1-42) but not tau levels than control subjects without an APOE epsilon4 allele (p < .01). As expected, the AD patients had lower levels of CSF beta-amyloid(1-42) and higher CSF tau levels than the normal control group (p < .01). CONCLUSIONS: The association of APOE epsilon4 allele and lower, more AD-like levels of CSF beta-amyloid(1-42) in older control subjects is consistent with previous studies showing possible neuroimaging and cognitive abnormalities with epsilon4 carriers and suggests that CSF beta-amyloid(1-42) decreases might represent an early biomarker of AD. Longitudinal follow-up is of course required to verify whether this biomarker is indeed predictive of clinical conversion to AD.

Context-specific memory and apolipoprotein E (ApoE) epsilon 4: cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease.

The aim of the study was to determine whether the epsilon 4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the epsilon 4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale-Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of epsilon 4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an epsilon 4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative epsilon 4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies.