Attention and brain function in Alzheimer's disease: A review.

Cognitive and neuroscience studies point to a selective impairment of attentional functions in Alzheimer's disease (AD). Prominent deficits occur in the shifting and division of attention, whereas phasic arousal and focused attention to stimulus features are only minimally affected in the early stages of AD. Macroscopic processing interpretations of these results—global cognitive impairment, generalized cognitive slowing, processing resource deficit, and failure of central executive control ("dysexecutive" syndrome)—are discussed. An alternative approach is based on the identification of component attentional operations and their mediation by corticocortical and subcortical networks. This analysis suggests that attention represents the first cognitive indicator of neocortical dysfunction in early AD. Disconnection between frontal and posterior parietal areas may mediate the selective disruption of attentional functions in AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conceptual implicit memory performance in Alzheimer's disease.

Alzheimer's disease (AD) patients often exhibit deficits on conceptual implicit memory tests such as category exemplar generation and word association. However, these tests rely on word production abilities, which are known to be disrupted by AD. The current study assessed conceptual implicit memory performance in AD patients and elderly control participants using a conceptual priming task that did not require word production (i.e., semantic decision). Memory performance was also examined using a category exemplar generation test (i.e., a conceptual priming task that required word production) and a recognition memory test. AD patients exhibited deficits on the semantic decision task, the category exemplar generation task, and the recognition memory task. The results indicate that the conceptual memory deficits observed in AD patients cannot be attributed completely to word production difficulties. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials

The cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) is used as an efficacy measure in clinical drug trials of Alzheimer's disease (AD). We used data from 1,648 AD participants in two identical 26-week multicenter drug trials to examine the distribution of baseline ADAS-Cog scores in relation to selected demographic and clinical variables, Mini-Mental State Exam (MMSE), Global Deterioration Scale (GDS), and Geriatric Evaluation by Relative's Rating Instrument (GERRI) scores. At baseline, the mean (+/-SD) MMSE score was 18 +/- 4, the ADAS-Cog score was 28 +/- 11, and most subjects were in GDS stage 4 or 5. The ADAS-Cog score was statistically significantly correlated with MMSE (R = -0.76, p < 0.0001) and GERRI (R = 0.40, p < 0.0001) total scores. Correlations among the ADAS-Cog items ranged from 0.19 to 0.59 and all were statistically significant (p < 0.0001). In a multiple regression model, younger age, male gender, older age at onset of dementia, use of concurrent estrogen, and use of concurrent anti-inflammatory agents were statistically significantly associated with superior cognitive performance. We also present data on the distribution of ADAS-Cog scores in relation to subjects' age, level of education, MMSE score, and GDS stage. Because age, MMSE score, and GDS stage (and not the ADAS-Cog) are commonly used to select subjects for AD clinical trials, our data should improve the ability of sponsors to predict ADAS-Cog scores of the subjects in their trials on the basis of the inclusion criteria used. Our data also suggest that age, gender, age at onset of dementia, level of education, and use of estrogen (in women) or anti-inflammatory drugs are related to cognitive abilities in AD. Further studies are needed to assess how and when cognitive differences related to these variables arise.     

Cognitive and neuropathologic correlates of Stroop Color-Word Test performance in Alzheimer's disease.

The Stroop Color-Word Test (SCWT; C. Golden, 1978) was examined in 59 patients with probable Alzheimer's disease (AD) and in 51 demographically comparable normal control (NC) participants. AD patients produced significantly larger Stroop interference effects than NC participants, and level of dementia severity significantly influenced SCWT performance. Principal -components analyses demonstrated a dissociation in the factor structure of the Stroop trials between NC participants and AD patients, suggesting that disruption of semantic knowledge and speeded verbal processing in AD may be a major contributor to impairment on the incongruent trial. Results of clinicopathologic correlations in an autopsy-confirmed AD subgroup further suggest the invocation of a broad network of integrated cortical regions and executive and language processes underlying successful SCWT performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavior and affect in Alzheimer's disease

The behavioral symptoms associated with AD are a critical aspect of the disease. They provide an additional avenue not only for understanding AD but for implementing interventions. The nature of behavioral disorders in AD is complicated by a number of factors that interact and contribute to the development of problematic behavior. It is difficult to determine whether the behavior is the result of neurodegeneration, cognitive dysfunction, previous experiences, current stressors, independently coexisting psychopathology, or a combination of these factors. In any case, behavioral disturbances need to be more clearly defined and objectively measured. To understand and treat behavioral disturbances in AD, all biopsy-chosocial factors must be examined simultaneously. Currently, there is little that can be done to treat the cognitive components of AD. Consequently, our most successful and beneficial interventions may focus on the remediable behavioral manifestations of the disease. The most valuable treatment approach for patients with AD and their caregivers interweaves medications, psychosocial services, environmental strategies, and caregiver education.     

Time of day variations in driving performance

A 25-year-old woman complained of anasarca and was admitted to Sakura National hospital on the presumptive diagnosis of nephrotic syndrome with 10.7 g of 24-hour urinary protein. At first, lupus nephritis with antiphospholipid antibody syndrome was suspected because of prolongation of APTT, existence of lupus anticoagulant and elevation of serum anticardiolipin antibody titer (IgM) in addition to positive ANA, lymphocytopenia and the biologically false positive test for syphilis (BFPTS). On day 28 of hospitalization, renal biopsy findings revealed severe endocapillary cell damage, such as swelling and proliferation of endothelial cells, fragmentation and double contour of the basement membrane walls, which were located only in the capillary lumens with a few thrombi. Immunofluorescent micrography revealed the absence of specific immunoglobulin or complement deposit. Therefore, the diagnosis of lupus nephritis was negated as these findings were suggestive of characteristic glomerulopathy due to primary antiphospholipid antibody syndrome. She was treated initially with oral prednisolone 60 mg and intravenous infusion of heparin 20,000 units daily. Moreover, cyclophosphamide 750 mg was administered intravenously as pulse therapy on day 13 as her serum level of CH50 had fallen suddenly, and hemodialysis was necessary because her renal function had deteriorated and she was suffering from cough and orthopnea with overhydratin. After the combined therapy, BFPTS disappeared and APTT returned to the normal range: dialysis treatment was not required further after the 4th hemodialysis. Thereafter, renal function improved and complete remission of nephrotic syndrome was obtained. This patient was a case of primary antiphospholipid antibody syndrome in which endothelial cell damage was located exclusively in the capillary lumens and pulse cyclophosphamide therapy in addition to prednisolone and anticoagulant was effective. We present this instructive case to promote understanding of the pathogenesis of primary antiphospholipid antibody syndrome.     

Affective disorders in Alzheimer's disease

The links between depressive syndrome and Alzheimer's disease are problematic concerning the diagnosis and the therapeutic choice. The concepts of pseudo-dementia and late onset depression are shortly discussed. The hypothesis concerning the relationship between depression and Alzheimer's disease are summarized. The clinical data relevant for the diagnosis and the therapeutic guidelines are discussed.     

Mental-behavioral disorders in Alzheimer's disease

Behavioural and psychological disorders are often observed in Alzheimer's disease. Some are common, such as symptoms of depression, apathy, aggressivity, agitation, psychotic disturbances, disorders of sleep rhythm, etc. Many factors contribute to the aetiology of these disorders, mainly cerebral lesions, environmental changes, somatic illnesses, iatrogenic factors and psychological reaction mechanisms. Management must take each into account. Treatment comprises medication (symptomatic treatment of the various disorders, cholinergic treatment) and other means (adaptation of the inhabitation, informing family and friends, psychotherapy, etc.).     

Alzheimer's disease and depression.

Reviews the empirical literature available on the phenomenon of depression in Alzheimer's disease (AD). Although not extensively studied, there is accumulating evidence to suggest that depression affects a large number of patients with AD and can have profound effects on both the long-term functioning of these patients and the well-being of their caregivers. Thus far, the field is dominated by studies of prevalence. Considerably rarer are studies investigating etiology, association with other aspects of the disease, impact on patients and caregivers, assessment, and treatment. The conceptual issues, methodological differences, and implications of the studies that exist thus far are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blood pressure and Alzheimer's disease

To fulfill criteria for probable Alzheimer's disease (AD), patients must be free of cerebrovascular lesions that may explain the cognitive decline. These criteria probably lead to an underestimation of the links between risk factors for stroke and AD. However, the association between stroke and AD is probably more frequent than expected. Arterial hypertension is the most important risk factor for stroke. The aim of this study is to evaluate, from the literature, the possible relationship between blood pressure and AD. Cognitive performances are usually lower in patients with arterial hypertension. A longitudinal study revealed that patients with AD aged 79-85 are more likely to have had higher values of blood pressure 10 to 15 years earlier, and they usually have a spontaneous decline of blood pressure beginning 1 or 2 years before the onset of AD. The relationship between arterial hypertension and AD is probably due to the summation of Alzheimer pathology, white matter changes and cerebrovascular lesions. A possible consequence of these findings would be to prevent, or to postpone, AD by an early treatment of arterial hypertension. This is currently evaluated in drug trials.     

Oxidative alterations in Alzheimer's disease

The expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGF receptor ligand, was investigated in rat forebrain under basal conditions and after kainate-induced excitotoxic seizures. In addition, a potential neuroprotective role for HB-EGF was assessed in hippocampal cultures. In situ hybridization analysis of HB-EGF mRNA in developing rat hippocampus revealed its expression in all principle cell layers of hippocampus from birth to postnatal day (P) 7, whereas from P14 through adulthood, expression decreased in the pyramidal cell layer versus the dentate gyrus granule cells. After kainate-induced excitotoxic seizures, levels of HB-EGF mRNA increased markedly in the hippocampus, as well as in several other cortical and limbic forebrain regions. In the hippocampus, HB-EGF mRNA expression increased within 3 hr after kainate treatment, continued to increase until 24 hr, and then decreased; increases occurred in the dentate gyrus granule cells, in the molecular layer of the dentate gyrus, and in and around hippocampal pyramidal CA3 and CA1 neurons. At 48 hr after kainate treatment, HB-EGF mRNA remained elevated in vulnerable brain regions of the hippocampus and amygdaloid complex. Western blot analysis revealed increased levels of HB-EGF protein in the hippocampus after kainate administration, with a peak at 24 hr. Pretreatment of embryonic hippocampal cell cultures with HB-EGF protected neurons against kainate toxicity. The kainate-induced elevation of [Ca2+]i in hippocampal neurons was not altered in cultures pretreated with HB-EGF, suggesting an excitoprotective mechanism different from that of previously characterized excitoprotective growth factors. Taken together, these results suggest that HB-EGF may function as an endogenous neuroprotective agent after seizure-induced neural activity/injury.