Diagnostic impact of CSF biomarkers in a local hospital memory clinic.

BACKGROUND: CSF biomarkers amyloid-beta 1-42 (Abeta42), total tau (tau) and tau phosphorylated at threonine 181 (ptau-181) are useful diagnostic markers for Alzheimer's disease (AD). We examined the impact of these biomarkers in the diagnostic process in a non-academic memory clinic. METHODS: One hundred and nine patients with available CSF were included from the local hospital memory clinic. Initially, patients were clinically diagnosed, and the clinician indicated their confidence in the diagnosis. Next the CSF results were presented, and the clinician re-evaluated his initial diagnosis. The main outcomes were changes in initial diagnosis and diagnostic confidence. RESULTS: Forty-seven patients were initially diagnosed with AD, 26 were diagnosed with another type of dementia, 18 were diagnosed with mild cognitive impairment, and 18 received a non-dementia diagnosis. All biomarkers distinguished between AD and non-dementia (p < 0.01); tau and ptau-181 also distinguished AD from other types of dementia (p < 0.001). After CSF biomarker levels were revealed, 11 diagnoses changed. In 31% of the diagnoses, the clinician gained confidence, while in 10% confidence decreased. CONCLUSION: We found that knowledge of CSF biomarker profiles changed the diagnosis in 10% of the cases, and confidence in the diagnosis increased for one third of the patients.

Fragmentation of the rest-activity rhythm correlates with age-related cognitive deficits.

Aging affects both cognitive performance and the sleep-wake rhythm. The recent surge of studies that support a role of sleep for cognitive performance in healthy young adults suggests that disturbed sleep-wake rhythms may contribute to 'age-related' cognitive decline. This relationship has however not previously been extensively investigated. The present correlational study integrated a battery of standardized cognitive tests to investigate the association of mental speed, memory, and executive function with actigraphically recorded sleep-wake rhythms in 144 home-dwelling elderly participants aged 69.5 +/- 8.5 (mean +/- SD). Multiple regression analyses showed that the partial correlations of the fragmentation of the sleep-wake rhythm with each of the three cognitive domains (r = -0.16, -0.19, and -0.16 respectively) were significant. These associations were independent from main effects of age, implying that a unique relationship between the rest-activity rhythm and cognitive performance is present in elderly people.

Transcranial Doppler blood flow assessment in patients with mild heart failure: correlates with neuroimaging and cognitive performance.

Cardiac output and cerebral perfusion are reduced in patients with advanced stages of heart failure. Our aim was to determine whether cerebral blood flow velocity measured by transcranial Doppler ultrasonography was reduced in outpatients with mild heart failure in comparison to controls and, if so, whether this reduction was related to cognitive performance and abnormalities of the brain diagnosed by magnetic resonance imaging.

The role of white matter hyperintensities and medial temporal lobe atrophy in age-related executive dysfunctioning.

Various studies support an association between white matter hyperintensities (WMH) and deficits in executive function in nondemented ageing. Studies examining executive functions and WMH have generally adopted executive function as a phrase including various functions such as flexibility, inhibition, and working memory. However, these functions include distinctive cognitive processes and not all may be affected as a result of WMH. Furthermore, atrophy of the medial temporal lobe (MTA) is frequently observed in ageing. Nevertheless, in previous studies of nondemented ageing MTA was not considered when examining a relationship between white matter and executive function. The goal of the present study was to examine how WMH and MTA relate to a variety of executive functions, including flexibility, fluency, inhibition, planning, set shifting, and working memory. Strong correlations were observed between WMH and MTA and most of the executive functions. However, only MTA was related to flexibility and set shifting performance. Regression analysis furthermore showed that MTA was the strongest predictor of working memory, after which no further significant association with WMH was noted. Alternatively, both MTA and periventricular hyperintensities independently predicted inhibition performance. These findings emphasize the importance of MTA when examining age-related decline in executive functioning.

Cognitive impairment in heart failure: a systematic review of the literature.

BACKGROUND: Heart failure (HF) and cognitive impairment are common medical conditions that are becoming increasingly prevalent in the aging Western population. They are associated with frequent hospitalisation and increased mortality, particularly when they occur simultaneously. Evidence from a number of studies suggests that HF is independently associated with impairment in various cognitive domains. AIMS: This systematic literature review evaluates the relation between cognitive deterioration and heart failure. METHODS: We searched electronic databases from 1966 to May 2006 for studies that investigated cognitive function in HF patients. Twenty-two controlled studies that met the inclusion criteria were selected for analysis. Study characteristics and data on global cognitive performance, memory scores, psychomotor speed and depression scores were extracted and analysed using the Cochrane Review Manager software. RESULTS: Pooled analysis shows diminished neuropsychological performance in HF patients, as compared to control subjects. In a pooled sample of 2937 heart-failure patients and 14,848 control subjects, the odds ratio for cognitive impairment was 1.62 (95% confidence interval:1.48-1.79, p<0.0001) among subjects with HF. CONCLUSION: This review confirms the relationship between HF and cognitive impairment, but it also stresses the need for additional systematic neuropsychological data and adequate neuro-imaging from representative populations of HF patients.

Brain magnetic resonance imaging abnormalities in patients with heart failure.

BACKGROUND: Although heart failure (HF) is a common cardiovascular disorder, to date little research has been conducted into possible associations between HF and structural abnormalities of the brain. AIMS: To determine the frequency and pattern of magnetic resonance imaging (MRI) abnormalities in outpatients with chronic HF, and to identify any demographic and clinical correlates. METHODS: Brain MRI scans were compared between a sample of 58 HF patients, 48 controls diagnosed with cardiovascular disease uncomplicated by HF (cardiac controls) and 42 healthy controls. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated. RESULTS: Compared to cardiac and healthy controls, HF patients had significantly more WMH, lacunar infarcts and MTA, whereas cardiac controls only had more MTA, compared to healthy controls. Age and left ventricular ejection fraction (LVEF) were independently associated with total WMH. Age and systolic hypotension were associated with MTA in HF patients and cardiac controls. CONCLUSION: Our results suggest that cardiac dysfunction contributes independently to the development of cerebral MRI abnormalities in patients with HF. Age and low LVEF are the principal predictors of cerebral WMH in patients with HF and in cardiac controls.

Neuroimaging and correlates of cognitive function among patients with heart failure.

BACKGROUND/AIMS: We purposed to investigate the relationship between cerebral abnormalities detected by magnetic resonance imaging (MRI) and cognitive performance in nondemented outpatients with heart failure (HF). METHODS: In 58 patients with HF neuropsychological assessment was performed including tests of mental speed, executive functions, memory, language and visuospatial functions. Deep, periventricular and total white matter hyperintensities (WMH), lacunar and cortical infarcts, global and medial temporal lobe atrophy (MTA) were investigated on MRI of the brain. Correlations between MRI findings and the cognitive measures were calculated. RESULTS: MTA correlated with memory (r = -0.353, p < 0.01), with executive functions (r = -0.383, p < 0.01) and the Mini Mental State Examination (r = -0.343, p < 0.05). Total WMH and deep WMH were found to correlate with depression and anxiety scores, but not with cognitive measures. Age, estimated premorbid intelligence and MTA were independent predictors of diminished cognitive performance. CONCLUSIONS: In HF patients, MTA was related to cognitive dysfunction, involving memory impairment and executive dysfunction, whereas WMH was related to depression and anxiety.

Assessing mental flexibility: neuroanatomical and neuropsychological correlates of the Trail Making Test in elderly people.

The Trail Making Test part B (TMT-B) is highly sensitive to age-related changes in the brain and cognitive function. However, the precise contribution of periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), and medial temporal lobe atrophy (MTA) to task performance remains unspecified. Similarly, diminished performance may be due to deficient flexibility functions, but also to other age-related cognitive decline (e.g., mental slowing). The aim of the present study was to determine neuroanatomical (PVH, DWMH, MTA) and neuropsychological (working memory, executive function, speed and attention, episodic memory) predictors of TMT-B performance in elderly people. Results showed that MTA was the strongest predictor of TMT-B performance. The predictive value of the neuropsychological scores differed among the various TMT-B variables. For example, all neuropsychological domains predicted the TMT-B total completion time, whereas only executive function predicted the ratio score (TMT-B/A). We conclude that MTA is a very important predictor of TMT-B performance in elderly people. Furthermore, multiple cognitive functions are involved in TMT-B performance and a mild decline in any of these functions may result in diminished TMT-B performance. Therefore it is crucial to use the ratio score when one wishes to examine executive function ability.

Profile of cognitive impairment in chronic heart failure.

OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates. DESIGN: Case-control study. SETTING: Outpatient clinic in a community hospital. PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated. MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z-scores for five cognitive domains and mean z-score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z-score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis. RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent (P=.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E epsilon4 allele. CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF.