Dementia Function Research Articles

Paying attention to acetylcholine: the key to wisdom and quality of life?

Publisher Summary This chapter focuses on attention and its important role in cognition. The chapter discusses the relationship between attentional mechanisms and higher order cognitive processes such as frontal lobe functions in health and disease, and speculates about the relationship between attention and wisdom. The higher order cognitive abilities depend on attention. In particular intimately related to arousal and attention are executive functions, also called frontal lobe functions, although their biological substrates involve many brain regions. The chapter reviews the cholinergic hypothesis particularly as it relates to the role of nicotine in attention. The effects of cholinergic drugs in Alzheimer's disease (AD) and other dementias are also discussed. The chapter presents data on the effects of cholinergic drugs in normal individuals and discusses the implications for cholinergic cognitive enhancement. Several cholinesterase inhibitors are available around the world, and are of relatively comparable efficacy although they vary somewhat in their side effects. Clearly, these drugs are only the first efforts to improve the cognitive function in dementias and represent some modest success for rational drug development.

Dawn–dusk simulation light therapy of disturbed circadian rest–activity cycles in demented elderly

We investigated whether low intensity dawn–dusk simulation (DDS), a ‘naturalistic’ form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest–activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85 yr old±5 yr, MMSE 14±5; n=9 DDS versus n=4 ‘placebo’ dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest–activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14 h earlier during treatment ( p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened ‘sleep latency’, longer ‘sleep duration’, more nocturnal immobility and less nocturnal activity than the dim red group ( p<0.1). In parallel, nighttime light exposure tended to be reduced ( p=0.07). These promising findings—after only 3 weeks of light treatment in elderly patients with advanced dementia—suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.

Flash Visual Evoked Potentials of Various Derivations in Dementia of the Alzheimer Type and Vascular Dementia

Background: Recently, evoked potentials have been used for objective monitoring of the cortical function in dementia. The aim of this study was to distinguish dementia of the Alzheimer type (DAT) from vascular dementia (VaD) using flash visual evoked potentials of various derivations. Methods: A total of 70 patients consulting Tachikawa Medical Center Kashiwazaki Kosei Hospital were divided into four groups, normal adult (29.5 ± 8.5 years, n=16), normal elderly (77.2 ± 4.7 years, n=17), VaD (81.1 ± 8.1 years, n=17) and DAT (77.4 ± 5.6 years, n=20). Red flash stimulation was provided by a pair of goggles. Visual evoked potentials (VEPs) to flash were recorded in accordance with the International 10–20 Electrode System. Results: The latencies of N130 and P190 of frontal and central derivations were significantly reduced in DAT compared with all other groups (p&lt;0.05). The N130 and P190 latencies were markedly delayed in the normal elderly group compared with the normal adult group (p&lt;0.05). The P3 (P100) latency of occipital derivation was significantly delayed in normal elderly, VaD and DAT groups compared with the normal adult group (p&lt;0.05). In the DAT group, the P190 latency was shortened at central and frontal derivations compared with that at occipital derivation (p&lt;0.05). Conclusions: The N130 and P190 latencies decreased at frontal and central derivations in DAT. While the reason is still unclear, dysfunction in the central visual system induced by the degeneration of neuronal populations in DAT may cause the apparently reduced latency. Flash VEPs of frontal and central derivations may be useful for the differential diagnosis of DAT from VaD.

Effects of Rivastigmine on Cognitive Function in Dementia with Lewy Bodies: A Randomised Placebo-Controlled International Study Using the Cognitive Drug Research Computerised Assessment System

This study was designed to assess the effects of rivastigmine (Exelon^®) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.

Examining neurochemical determinants of inspection time: Development of a biological model

Inspection time (IT), an information-processing correlate of psychometric intelligence, has been extensively studied. Previous research has shown that IT is a reliable correlate of psychometric intelligence across different developmental periods, mirroring developmental trends of fluid intelligence. Despite this extensive previous literature, very little is known about the biological basis of IT. In the present review, we discuss recent results from our laboratories examining the neurochemical determinants of IT. In this review, we outline the significance of several studies in which performance on the IT task is measured before and after modulating key human central nervous system (CNS) neurotransmitters and receptor systems (e.g., cholinergic, serotonergic, noradrenergic, and dopaminergic systems). The results of these studies indicate a primarily cholinergic basis for IT, although other aspects of psychometric intelligence may have serotonergic and dopaminergic determinants in addition to a cholinergic basis. The results are consistent with data reporting cholinergic depletion and impaired IT performance in dementia of the Alzheimer's type (DAT). Speculatively, we propose that compounds that enhance the release of the neurotransmitter acetylcholine (Ach) will improve IT and the variance that IT shares with IQ test performance.

Relationship of psychosis to aggression, apathy and function in dementia

Relationship of psychosis to aggression, apathy and function in dementia

Relationship of psychosis to aggression, apathy and function in dementia.

Psychosis has been associated with aggression in dementia, but the nature of this relationship has been unclear. There has been very little research into the relations between apathy and functional status to psychosis in dementia. The purpose of this study is to investigate the relationship between psychosis and aggression, apathy, and functional status in outpatients with dementia. The presence of psychosis was assessed by clinical interview and two scales: the Neuropsychiatric Inventory and the Columbia University Scale for Psychopathology in Alzheimer's Disease. The maximum likelihood estimation technique was used to determine the best estimate of the presence of psychosis. Aggression, apathy, and functional status (activities of daily living: ADLs) were measured using structured instruments. Sixty-one subjects were included. The CUSPAD and NPI provided low false positive and negative rates. ANCOVA analyses showed that psychosis was significantly associated with aggression, even when controlling for apathy, depression, and ADLs. Psychosis was related to apathy only when depression was controlled for. Hallucinations were related to impaired basic ADLs, even when depression and apathy were controlled for. Relationships were found between psychotic symptoms in dementia and aggression as well as apathy and impaired functional status. These relationships suggest pathophysiologic mechanisms and have possible treatment implications.

Improving Function in Dementia and Other Cognitive-Linguistic Disorders: A Guide and Resource Book

Improving Function in Dementia and Other Cognitive-Linguistic Disorders: A Guide and Resource Book

Intellectual, Mnemonic, and Frontal Functions in Dementia with Lewy Bodies: A Comparison with Early and Advanced Parkinson’s Disease

Both Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share a common neuropathological marker, the presence of Lewy bodies in brain stem and basal forebrain nuclei. DLB, in addition, is associated with Lewy bodies in the neocortex, and, in it's more common form, with Alzheimer-type pathological markers, particularly amyloid plaques. Published neuropsychological studies have focused on the differential profiles of DLB and Alzheimer's disease (AD). However, it is presently unclear whether DLB should be classified as a variant of AD or PD. In the present study we compare a healthy age-matched control group with three groups of patients, one with DLB, and two with PD. One of the PD groups was early in the course (PD-E) and the second, more advanced group (PD-A), was matched on severity of cognitive impairment with the DLB group. The results show that DLB was associated with a different pattern of neuropsychological impairment than the PD-A group, particularly in tests believed to be mediated by prefrontal cortical regions.

Subjective appraisals of memory functioning in dementia: Validity and cautions

Subjective appraisals of memory functioning in dementia: Validity and cautions

Predictors of Longitudinal Changes in Memory, Visuospatial, and Verbal Functioning in Very Old Demented Adults

Longitudinal changes in memory, visuospatial and verbal functioning in a sample of demented persons were examined. The role of several demographic, psychometric, and biological indices in predicting the rate of cognitive deterioration was also investigated. The sample consisted of 31 very old (mean age at entry = 83.5 years, range = 75–95) persons with Alzheimer’s disease (n = 22) and vascular dementia (n = 9) from a community-based study. Subjects were tested on two occasions separated by approximately 2.5 years. Results indicated significant longitudinal decline in verbal fluency and visuospatial ability, but only on 1 of 3 measures of episodic memory. Results from regression analyses indicated that a variety of putatively important variables, including age, gender, education, digit span, as well as a number of biological (vitamin B₁₂, TSH), dementia etiology, and psychometric (digit span) indicators, exhibited no relationship to rate of memory, visuospatial, or verbal decline. The results suggest that the rate of cognitive deterioration in dementia is highly variable, and this variability in change appears to include a variety of characteristics. A possible reason thereof may be that the role of individual-difference variables for cognitive functioning in dementia is overshadowed by the pathogenetic process itself.

Quantitative Evidence for Neuroanatomic and Neuropsychological Markers in Dementia of the Alzheimer's Type

Meta-analytic methods were used to determine the sensitivity of neuropsychological, structural, and physiological measures to temporal-hippocampal system function in dementia of the Alzheimer's type. Effect sizes are reported for the California Verbal Learning Test, the Wechsler Memory Scale-Revised, structural (i.e., magnetic resonance imaging [MRI]), and functional (i.e., positron emission tomography [PET], single photon emission computed tomography [SPECT]) neuroimaging methods. Overall, effect sizes from MRI studies are larger than those obtained from SPECT and PET, respectively, but not as large as those obtained from the neuropsychological measures. On the basis of this finding, the neuropsychological and gross pathologic similarities between Alzheimer's disease, other dementing conditions, and mixed dementias, warrants the coupling of neuropsychological evaluation for its sensitivity with neuroimaging visualization for its specificity in improving diagnostic and differential accuracy.

A Snapshot of Psychogeriatric Research in Australia

A survey of academic departments specialising in psychogeriatrics was undertaken in order to provide a picture of current research in this area. Reports from departments in seven universities demonstrate strong performance in dementia, depression and care research, and burgeoning interest in nursing home and biological areas.

Loss of high-frequency brain electrical response to thiopental administration in alzheimer's-type dementia

Abnormal brain regions generate proportionately less high-frequency (beta) activity than nonpathological regions, a phenomenon accentuated by barbiturate administration. Using quantitative electroencephalography we examined power in the 20- to 28-Hz band in patients with dementia of the Alzheimer's type (DAT), vascular dementia (VaD), and normal elderly controls (CON) following an IV bolus of thiopental (0.5 mg/kg). Compared to both CON and VaD subjects, DAT subjects showed a marked loss of beta power elicited across the cortex, with largest differences noted in the frontal region. Losses were most significant for the peak response recorded at 30 to 90 s postinjection and persisted during the 5-minute follow-up period. We hypothesize that differences in this electrocerebral response reflect differences in the underlying neuropathology of DAT and VaD subjects. A thiopental challenge may be well suited for the in vivo assessment of brain function in dementias characterized by prominent cortical pathology.

The role of selective attention in driving and dementia of the Alzheimer type.

This paper examines the relationship between cognitive processes and driving in aging and dementia of the Alzheimer type. Several studies that have explored the relationship between neuropsychological test performance and various indicators of driving safety are reviewed. It is argued that deficits in selective attention are specific to impaired driving performance in dementia of the Alzheimer type. Results from a recent study supporting this notion are presented. It is suggested that screening measures that emphasize the ability to selectively attend to relevant information and inhibit irrelevant information should be used to identify mildly demented individuals who are at risk for unsafe driving.

Quantitative magnetic resonance imaging and neuropsychological functions in dementia of the Alzheimer type.

The aim of the present study was to investigate neuropsychological functions in dementia of the Alzheimer type (DAT) with respect to morphological changes that were revealed by quantitative magnetic resonance imaging (MRI). Twenty patients with DAT (NINCDS-ADRDA criteria) and 10 healthy age and sex matched controls were included. The neuropsychological function was evaluated on a test battery covering the severity of dementia, verbal and visual memory, concentration and attention, language skills and general intelligence as well as activities of daily living. 3D MRI sequences were acquired using a 1.5 T Siemens MAGNETOM. Whole brain volume, total intracranial volume (TIV), volume of the frontal and temporal lobes and volumes of the amygdalahippocampus complex (AHC) were assessed using the newly developed software NMR Win. Apart from TIV all morphometric parameters differed significantly between the diagnostic groups. AHC volumes discriminated best between the groups, with only a small overlap. AHC atrophy exceeded generalized atrophy. These findings were confirmed when the data were reanalysed after dividing the DAT patients into a mildly and moderately affected group. The severity of dementia was significantly correlated with the volumes of the AHC and the volumes of the temporal lobes bilaterally, but not with the whole brain volume and the volumes of the frontal lobes. These results underline the important role of the temporal substructures for aetiology and progression of DAT. They indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.

Longitudinal examination of American National Adult Reading Test (AMNART) performance in dementia of the Alzheimer type (DAT): validation and correction based on degree of cognitive decline.

The American National Adult Reading Test (AMNART) was constructed to provide a valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals. However, recent studies have brought into question its validity in patients with dementia of the Alzheimer type (DAT). The present study was designed to longitudinally assess the validity of the AMNART in 40 DAT patients and 40 demographically matched normal control (NC) subjects. The results showed that VIQ estimates for patients with DAT were significantly lower than those of NC subjects and declined significantly over time with increasing dementia severity as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). An MMSE-based correction factor was derived for the DAT group which allows for the effective estimation of premorbid VIQ in these patients.

Issues in the Assessment of Cognitive Function in Dementia

The increasing prevalence of elderly patients presenting with disorders of cognitive functioning suggestive of dementia, coupled with limits in resources available to address these problems, is going to necessitate the development of new technologies to be used for assessment. These measures should be efficient, designed to reflect both the current knowledge of brain function and the developmental characteristics of older patients. Though few current measures of cognitive function meet these goals, neuropsychological “microbatteries” such as the DRS and NCSE may serve as models for a new generation of cognitively specific assessment instruments.

The effect of white matter low attenuation on cognitive performance in dementia of the Alzheimer type.

The effect of leukoaraiosis or white matter low attenuation (WMLA) on cognitive function is not fully understood. We compared the neuropsychological performance of 37 Alzheimer's disease patients with WMLA on CT brain scans with a similar group of 31 Alzheimer's disease patients with no evidence of white matter lesions. Patients with WMLA performed significantly worse on tests of visuospatial function (Cube Analysis test, p = 0.004), and cognitive speed (Kenrick Digit Copying test, p = 0.05) compared to those with no visible white matter lesions. Patients with widespread WMLA performed generally worse in tests of cognitive function than those with frontal or a mixture of frontal and occipital WMLA. This was most significant in the areas of attention (forward digit span, p = 0.003), visual recognition (p = 0.004), and cognitive speed (p = 0.03). There is an association between impaired cognitive performance and the presence of WMLA in Alzheimer's disease patients, with WMLA probably contributing to the cognitive impairment. This is most evident in patients with widespread white matter lesions.

202 Five-year follow-up study of demented residents tested with the Dementia Functioning in Daily Living (DFDL) scale

202 Five-year follow-up study of demented residents tested with the Dementia Functioning in Daily Living (DFDL) scale