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.     

Drugs used in Alzheimer's disease and neuroplasticity

Drugs indicated for use in Alzheimer's disease (AD) must clinically improve the cognitive symptomatology of the disorder, although nonexclusively. From a neurochemical standpoint, these drugs must oppose the multiple processes recognized as stigmata of AD. In these two ways, so-called AD drugs may be considered substances modifying cerebral plasticity. Long-term evaluation of anticholinesterases and of tacrine, in particular, provides arguments in support of this initially purely biologic, theoretical approach. This concept of neuroplasticity applied to dementia may modify the traditional pharmaceutical drug development programs.     

Alerting and orienting in Alzheimer's disease.

Recently, researchers (E. Festa-Martino, B. R. Ott, & W. C. Heindel, 2004, see record 2004-12990-007; A. Tales, J. L. Muir, A. Bayer, R. Jones, & R. J. Snowden, 2002; A. Tales, J. L. Muir, A. Bayer, & R. J. Snowden, 2002; see record 2002-06031-015) have found significantly abnormal spatial orienting together with the abolishment of the alerting effect in Alzheimer's disease (AD). However, these research groups differed in their interpretation of the results. A. Tales, J. L. Muir, A. Bayer, R. Jones, and R. J. Snowden (2002) and A. Tales, J. L. Muir, A. Bayer, and R. J. Snowden (2002) explained their data in terms of two independent processes, whereas E. Festa-Martino et al. (2004) interpreted their findings as indicative of an inverse association, namely that the increased spatial orienting effect in AD was the direct result of the abolition of the phasic alerting effect. In this further study examining exogenous spatial orienting and phasic alerting, the authors present evidence to suggest that the increased spatial orienting effect in AD is not the result of a decreased phasic alerting effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention and driving performance in Alzheimer's disease

The present study examined the relationship between visual attention measures and driving performance in healthy older adults and individuals with very mild and mild dementia of the Alzheimer type (DAT). Subjects were administered an on-road driving assessment and three visual attention tasks (visual search, visual monitoring, and useful field of view). The results indicated that error rate and reaction time during visual search were the best predictors of driving performance. Furthermore, visual search performance was predictive of driving performance above and beyond simple dementia severity and several traditional psychometric tests. The results suggest that general cognitive status may be useful for identifying individuals "at risk" for unsafe driving. However, measures of selective attention may serve to better differentiate safe versus unsafe drivers, especially in the DAT population.