WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Iatrogenic amnesia is one of the main aetiologies of transient amnesia.• Benzodiazepines and anticholinergic drugs are considered to be the drugs most often responsible for iatrogenic amnesia.• The impact of drugs in memory disorders is particularly pronounced in elderly people, especially due to polymedication.WHAT THIS STUDY ADDS• An association between memory disorders and some drugs, such as benzodiazepines, antidepressants and older anticonvulsants, was found as expected.• A strong association was found with unexpected drugs, such as benzodiazepine‐like hypnotics (zopiclone and zolpidem), serotonin reuptake inhibitor antidepressants and newer anticonvulsants.• Non‐neurotropic drugs, such as isotretinoin and ciclosporin, were also associated with memory disorders.AIMS To investigate putative associations of reports of memory disorders and suspected drugs.METHODS We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of memory loss in the FPVD between January 2000 and December 2009. Noncases were all other reports during the same period. To assess the association between memory impairment and drug intake, we calculated an odds ratio with its 95% confidence interval.RESULTS Among the 188 284 adverse drug reactions recorded, we identified 519 cases of memory loss. The sex ratio was 0.6 and the median age was 54 years (range 4–93). The maximal number of cases occurred between 40–49 and 50–59 years. Evolution was favourable in 63% of the cases. We found significant odds ratios for benzodiazepines (alprazolam, bromazepam, prazepam, clonazepam etc.), benzodiazepine‐like hypnotics (zolpidem and zopiclone), antidepressants (fluoxetine, paroxetine and venlafaxine), analgesics (morphine, nefopam and tramadol), anticonvulsants (topiramate, pregabalin, levetiracetam etc.), antipsychotics (aripiprazole and lithium) and other drugs, such as trihexyphenidyl, ciclosporin and isotretinoin.CONCLUSIONS Our study confirmed an association between memory disorders and some drugs, such as benzodiazepines and anticonvulsants. However, other drugs, such as benzodiazepine‐like hypnotics, newer anticonvulsants, serotonin reuptake inhibitor antidepressants, isotretinoin and ciclosporin were significantly associated with memory disorders, although this was not described or poorly described in the literature.Taking account of the limits of this study in the FPVD (under‐reporting, notoriety bias etc.), the case/noncase method allows assessment and detection of associations between exposure to drugs and a specific adverse drug reaction, such as memory disorders, and could thus generate signals and orientate us to further prospective studies to confirm such associations.

Alzheimer's disease (AD), the most common form of dementia in the older people, is a multifactoral pathology, characterized by cognitive deficits, increase in cerebral deposition of the ␤-amyloid (A␤) peptide, neurofibrillary tangles, and neurodegeneration. Studies currently support a central role of neuroinflammation, through production of proinflammatory cytokines including excess tumor necrosis factor ␣ (TNF-␣) in the pathogenesis of AD, especially in A␤-induced cognitive deficits. Imipramine, a tricyclic antidepressant, has potent anti-inflammatory and neuroprotective effects. This study investigates the effect of imipramine on alterations of long-term and short-term memories, TNF-␣ expression, and amyloid precursor protein (APP) processing induced by intracerebroventricular injection of A␤25-35 in mice. Mice were treated with imipramine (10 mg/kg i.p. once a day for 13 days) from the day after the A␤25-35 injection. Memory function was evaluated in the water-maze (days 10 -14) and Y-maze (day 9) tests. TNF-␣ levels and APP processing were examined in the frontal cortex and the hippocampus (day 14). Imipramine significantly prevented memory deficits caused by A␤25-35 in the water-maze and Y-maze tests, and inhibited the TNF-␣ increase in the frontal cortex. Moreover, imipramine decreased the elevated levels of A␤ both in frontal cortex and hippocampus with different modulations of APP and C-terminal fragments of APP. So, imipramine prevents memory impairment through its intrinsic property to inhibit TNF-␣ and A␤ accumulation and may represent a potential candidate for AD treatment.Alzheimer's disease (AD), the most common form of dementia in older people is associated with cognitive deficits. Indeed, brains of individuals who have AD manifest massive neuronal and synaptic loss in certain areas that result in memory impairment and disorientation associated mainly with late stages of the disease. However, in the early stages, the etiology of these cognitive dysfunctions is unclear. AD is a multifactoral pathology, characterized not only by an increase in cerebral deposition of the ␤-amyloid (A␤) peptide, the major constituent of senile plaques that can potentially cause cognitive impairments, but also by neuroinflammation, oxidative damage, and neurodegeneration in critical brain regions (hippocampus, frontal cortex) also involved in memory and cognition

Parkinson's disease (PD) is characterized by a triade of motor symptoms due to the degeneration of nigrostriatal pathway. In addition to these motor impairments, cognitive disturbances have been reported to occur in PD patients in the early stage of the disease. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin widely used to produce experimental models of PD. In a previous work, we showed that MPTP altered the expression of proteins involved in mTOR antiapoptotic and PKR apoptotic pathways of translational control (TC) in neuroblastoma cells. In the present study, the results indicated that a subchronic MPTP intoxication in mice decreased the dopaminergic neuron number, produced an activation of PKR way and an inhibition of mTOR way of TC especially in striatum and frontal cortex associated with a great activation of PKR in hippocampus. Moreover, in parallel to biochemical analysis, the mnesic disturbances induced by MPTP were characterized in C57Bl/6 mice, by testing their performance in three versions of the Morris Water Maze task. Behavioral results showed that the MPTP lesion altered mice learning of a spatial working memory, of a cued version and of a spatial reference memory task in the water maze. Furthermore, we previously demonstrated that the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) could counteract the MPTP toxicity on TC factors in neuroblastoma cells. Thus, the second objective of our study was to assess the PACAP effect on MPTP-induced TC impairment and cognitive deficit in mice. The pretreatment with PACAP27 by intravenous injections partially protected TH-positive neuron loss induced by MPTP, prevented the MPTP-induced protein synthesis control dysregulation and mnesic impairment of mice. Therefore, our results could indicate that PACAP may be a promising therapeutic agent in Parkinson's disease.

No abstract

We suggest that renal lesions that develop before birth may persist after withdrawal of the causative drugs and normalization of blood and renal perfusion pressure. Their persistence could explain the severe long-term outcome of some of these patients. Long-term study of children exposed to RAS blockers during fetal life is strongly recommended.