Dementia and depression are common psychiatric disorders in the elderly. Alzheimer's Disease (AD) is a progressive neurodegenerative disorder with specific histopathological hallmarks and characteristic clinical features such as progressive decline in cognition and daily living abilities. In addition, as in depression in the elderly, depressed mood, anxiety, agitation, irritability and restlessness frequently occur. Recent studies suggest that depression, cognitive impairment and degenerative dementia might be considered as intersecting continua. Five prototypical groups along these continua were proposed, among these were depressive dementia and the depression of degenerative dementia. Depressive dementia was described as a reversible major depressive disorder with clinically relevant cognitive impairments. This entity was related to dysfunctions in the limbic-thalamic-cortical circuit, consisting of the amygdala-hippocampus complex, the mediodorsal thalamus, the basal ganglia and the dorsolateral prefrontal cortex. Up to 30-40% of patients with dementia also show symptoms of a major depression. Here, dementia is the primary diagnosis and depression is secondary. The concomitant presence of dementia may impair the recognition and reporting of depressive symptoms. However, it remains still unclear whether depressed mood in the elderly is an early sign or a risk factor of dementia. Common overlapping pathophysiological mechanisms, such as biogenic amine deficiencies, may be associated with both disorders. A substantial loss of cortical cholinergic neurons in patients with AD has been considered to be the major pathophysiological correlate of cognitive impairment. Therefore, cognition enhancing therapies have focussed on activating this system and brain specific acetylcholinesterase inhibitors as well as selective muscarinic M 1 -agonists have been developed. However, transmitter deficiencies are not restricted to cholinergic pathways but include a variety of other neurotransmitters, such as serotonin and noradrenaline. Reduced concentrations of serotonin and of its major metabolite 5-hydroxyindole acetic acid (5-HIAA) in cerebral tissue and cerebrospinal fluid were reported in several psychopathological states and have been associated with serotonergic dysfunctions including irritability, suicide attempts, insomnia, aggressive behaviour and anxiety. In view of the multiple neurotransmitter deficiencies in AD, a single transmitter-based treatment strategy might not be sufficient. In addition, although the basic biochemical dysfunctions in depression are still not completely known, serotonin and noradrenaline have been considered to be crucially involved in the pathogenesis of affective disorders.In conclusion, antidepressants may be useful in the treatment of dementia because, first, a large number of patients with AD meet the criteria for a major depression (leading to an additional secondary impairment of cognitive functions), and, secondly, neurodegeneration in AD is associated with cholinergic as well as noradrenergic and serotonergic deficiencies. These considerations are in well agreement with improvements of cognition by particular antidepressants.Antidepressants in dementia: Pharmacological treatment in aged patient populations with traditional antidepressants may evoke difficult clinical situations. Altered pharmacokinetics and pharmacodynamics associated with ageing, accompanying physical disorders, such as cardiovascular disease or prostate hypertrophy, as well as common polypharmacy in the elderly, have to be considered. The recommendation start low, go slow should strictly be followed. Many of the classical antidepressants available today are of comparable clinical efficacy, but may differ in terms of tolerability. Compounds like tricyclic antidepressants (TCAs) are characterized by a high potential of anticholinergic side-effects including memory impairments, delirium, behavioural toxicity and cardiovascular dysfunctions. Demented patients appear particularly susceptible to these effects, probably due to diminished capacities in central regulatory systems.The sedative and anticholinergic properties of tricyclics may substantially impair performance of psychomotor skills, cognitive tasks and daily living abilities.In the search for new antidepressants with fewer adverse effects a large number of new compounds have been recently developed and introduced into the market. Selective serotonin reuptake inhibitors (SSRIs), and Moclobemide, a reversible monoamine oxidase-A inhibitor (MAOI), and Venlafaxine have been demonstrated to be as efficient as traditional TCAs in the treatment of depression.Currently, there are five SSRIs available in Europe: Citalopram, Fluoxetine, Fluvoxamine, Paroxetine and Sertraline. Their clinical efficacy and tolerability have been demonstrated in a large number of double-blind-controlled studies. The antidepressant, anxiolytic and antiaggressive effects, the lack of sedative and anticholinergic properties and the wide therapeutic window suggest that these compounds may be useful in the treatment of patients with both dementia and emotional disturbances. Studies with Citalopram in AD patients showed improvements in the GBS (Gottfries-Brane-Steen) ratings of confusion, irritability, anxiety, depressed mood and restlessness. On the basis of meta-analyses of 67 published randomized controlled clinical trials it can be concluded that SSRIs have a significant and clinically relevant advantage over classical TCAs with respect to tolerability, whereas the clinical efficacy is similar. In addition, SSRIs appear to improve clinically relevant cognitive functions, e.g. demonstrated in the GBS scale. Whether there are differences in this respect among the various SSRIs requires further clarification.The clinical efficacy of MAOIs has been demonstrated in a wide range of psychiatric disorders and psychopathological states such as agoraphobia, panic attacks, anergia and somatic anxiety, due to its anxiolytic, antiphobic and antidepressive properties. In addition, Moclobemide seems to be free of behavioural toxicity. It enhances cognition associated with a general stimulation in aged depressive patients. This effect might be due to its action on MAO-A, leading to an increase of noradrenergic, serotonergic and dopaminergic activity.Summary and Conclusions: Neuropathological and biochemical studies have clearly demonstrated multiple neurotransmitter dysfunctions in patients with AD involving cholinergic, serotonergic and noradrenergic pathways. These alterations have been associated with different psychopathological states, e.g. failing memory, anxiety, depression, agitation, irritability and aggressive behaviour. The new generation of antidepressants, in particular SSRIs and Moclobemide, may exert beneficial effects on cognition and behavioural disturbances in addition to the well-known antidepressive properties.