Dementia is one of the most frequent and disabling health problems of our times. During the past twenty years, we have witnessed growing public and professional interest in dementia, its diagnosis and causes. This has led to the introduction of better methods of detection of cognitive impairment, coupled with early diagnosis of Alzheimer's disease and, to a lesser degree, of other forms of dementia. However, if the clinical presentation of patients does not follow the typical pattern of progressive memory loss starting in later life, then currently available diagnostic methods are less likely to be useful and patients with dementia may go unidentified for prolonged periods of time. Some of the less frequent causes of dementia may initially present with psychological or behavioral disturbances, others are associated with prominent neurological signs and symptoms. Patients may also present with marked deficits in cognitive domains other than memory, such as impaired language, which makes the diagnostic workup more difficult and onerous.

The search for the possible causes of common and uncommon forms of dementia has a long and interesting history. This paper presents a brief review of how the concept of dementia has evolved over time and an historical outline of the causative factors associated with these disorders. Currently available evidence leads to the conclusion that there is only one common cause of dementia: Alzheimer's disease with or without other overlapping pathological processes (such as cerebrovascular disease, traumatic brain injury, etc.). All other forms of dementia are, in isolation, uncommon.

A brief review of classification in psychiatry from Kraepelin to ICD-10 and DSM-IV reveals that the categorical paradigm inherent in these nosological systems has certain inadequacies when applied to dementia specifically and cognitive impairment in general. There are “outcasts” from these two systems that, with the rapid advances in an understanding of cognitive disorders, expose significant limitations in them. As and when they are revised, serious consideration of a different view, accepting a dimensional paradigm, would contribute to a more inclusive and clinically relevant nosology for dementia and cognitive disorders.

When patients present with a dementia syndrome at a young age, the experienced clinician will automatically include uncommon dementias in the diagnostic considerations, as familial uncommon dementias due to genetic mutations frequently present as early-onset dementias. This paper highlights why uncommon dementias due to genetic mutations, although marginal in terms of prevalence numbers in the total population, are of significance in the quest to unravel the underlying cause of common dementias such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementias (FTD) and vascular dementia (VaD).

A group of neurodegenerative diseases is outlined that affect cortical and subcortical areas of the brain. These diseases give rise to atypical forms of dementia and, unlike Alzheimer's disease (AD), are often associated with neurological symptoms. Clinical symptoms reflect the localization of the degenerative process rather than the nature of the underlying histopathology. Degeneration of the frontal and anterior temporal lobe presents initially with behavioral alterations, but later in the course, impairment of cognition and activities of daily living develops. Posterior cortical atrophy affects the parietal and occipital association cortices and causes complex visual disturbances. In corticobasal degeneration (CBD) the focus of pathology includes the frontoparietal cortex and several subcortical nuclei, causing symmetrical rigidity, bradykinesia, myoclonus and dystonia. Progressive supranuclear palsy (PSP) involves the frontal, temporal and parietal cortex as well as parts of the brain stem. Clinical features include a hypokinetic rigid syndrome with nuchal dystonia and vertical gaze palsy. Huntington's disease is a prototypical autosomal dominant disorder that affects the extrapyramidal system and causes choreatic movements in combination with personality changes and cognitive deterioration. Amyotrophic lateral sclerosis (ALS) with dementia is a neurodegeneration of the frontotemporal cortex and of the anterior horn of the spinal cord. Behavioral change similar to frontotemporal dementia (FTD) is paralleled or followed by the classic features of motor neuron disease.

Background: The concept of Binswanger's disease (BD) remains unclear and may not constitute a useful diagnostic category. However, cognitive decline may be present in a proportion of patients with subarachnoid hemorrhages (SAH) or subdural hematomas (SH).

Method: We provide a critical review of the concept of BD and summarize the main findings on the association between SAH, SH and cognitive decline.

Results and conclusions: BD was originally identified as a type of dementia different from neurosyphilis and with characteristic white matter atrophy. The phenomenology of BD is currently construed around the concept of frontosubcortical dementia, but the validity of this construct is unclear. Patients with SAH frequently develop a variety of cognitive and behavioral problems that usually result in poor psychosocial adjustment and poor quality of life. SH is a rare cause of progressive cognitive impairment. A proportion of patients (particularly functionally impaired old individuals) are at a high risk for cognitive deficits after surgical drainage of the hematoma.

At the turn of the last century, infectious diseases represented an important cause of health morbidity and behavioral changes. Neurosyphilis, for example, was relatively common at the time and often led to the development of cognitive impairment and dementia. With the advent of effective antibiotic treatment, the association between infectious diseases and dementia became increasingly less frequent, although a resurgence of interest in this area has taken place during the past 15 years with the emergence of acquired immunodeficiency syndrome (AIDS) and variant Creutzfeldt–Jakob disease (vCJD). This paper reviews the most frequent infectious causes of dementia, including prion diseases, as well as infections caused by herpes virus, human immunodeficiency virus (HIV), toxoplasmosis, cryptococcus, cytomegalovirus, syphilis, borrelia and cysticercosis.

Deficiencies of vitamins B12, B3 and folate, abnormalities of cortisol metabolism, Wilson's disease, renal and hepatic failure, chronic obstructive pulmonary disease, hypo- and hypernatremia, thyroid and parathyroid dysfunction, hyper- and hypoglycemia and Marchiafava–Bignani disease are metabolic and endocrinological abnormalities that may be associated with cognitive impairment. In some cases these abnormalities may be causative of impaired cognition and in other situations merely associated with cognitive impairment. The existence of these conditions provides some justification for routine investigations commonly performed on patients presenting with possible early dementia.

Early retrospective studies suggested that individuals with a history of a traumatic brain injury (TBI) had a higher risk for dementia than those without a history of TBI. Two meta-analyses demonstrated that the risk for dementia is higher among men, but not women, with a history of TBI. More recent prospective studies, however, are providing discrepant findings, probably due to important methodological differences. TBI is usually associated with significant neuropsychological deficits, primarily in the domains of attention, executive functioning and memory. These deficits may not improve with time. TBI may also lower the threshold for the clinical expression of dementia among predisposed individuals, and the onset of Alzheimer's disease (AD)-like neuropathological and biochemical changes immediately after severe TBI may play an important role in this mechanism.

The acute use of alcohol and several other licit and illicit drugs can affect mental state and cognitive function. The chronic use of certain drugs may also increase the risk of cognitive impairment and perhaps dementia in later life. This paper focuses on the long-term cognitive consequences of using alcohol, benzodiazepines, tobacco and cannabis. Currently available evidence indicates that mild to moderate alcohol consumption is not associated with increased risk of cognitive decline and may in fact have a protective effect against dementia, although heavy, long-term consumption is likely to have a negative impact on cognitive function. The degree that alcohol-related cognitive impairment must reach to be classified as dementia is currently obscure. Longer-term smoking is associated with increased risk of cognitive impairment and possibly dementia. The chronic use of benzodiazepines has been associated with increased risk of cognitive impairment but information relating to dementia remains inconclusive. The chronic use of cannabis may impair intellectual abilities but data on this topic remain sparse and difficult to interpret. In conclusion, there is evidence that some drugs contribute to the causal pathway that leads to the development of cognitive impairment but currently available data do not support the introduction of a separate diagnostic category of drug-induced dementia (such as alcohol-related dementia). Health promotion programs designed to decrease tobacco smoking and “harmful” alcohol use (and possibly other drug use) may decrease the burden of cognitive impairment and perhaps dementia in later life.

Toxic causes of dementia include exposure to heavy metals such as lead, mercury and aluminum as well as to carbon monoxide and solvents. Autoimmune conditions include such entities as multiple sclerosis, systemic lupus erythematosus, Behçet's disease and Sjögren's syndrome. These conditions share broadly similar cognitive effects giving rise to impairments with subcortical features. Individuals are often affected at a relatively young age. Optimal preventative strategies include avoidance of toxic substances. Comprehensive neuropsychological assessment is valuable not only diagnostically and for monitoring but also to identify the patients' strengths and weaknesses, so that compensatory strategies can be recommended.

Several genetic disorders, though rare, are associated or present with dementia. Developments in the field of genetics are contributing to clarify and expand our knowledge of the complex physiopathological mechanisms leading to neurodegeneration and cognitive decline. Disorders associated with misfolded and aggregated proteins and lipid, metal or energy metabolism are examples of the multifarious disease processes converging in the clinical features of dementia, either as its predominant feature, as in cases of Alzheimer's disease (AD) or frontotemporal dementia (FTD), or as part of a cohort of accompanying or late-developing symptoms, as in Parkinson's disease (PD) or amyotrophic lateral sclerosis with dementia (ALS-D). Awareness of these disorders, allied with recent advances in genetic, biochemical and neuroimaging techniques, may lead to early diagnosis, successful treatment and better prognosis.

In this review, we explore the relationship between epilepsy and cognition and between epilepsy and dementia. Chronic epilepsy, particularly mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, may be associated with impaired cognition, which can be secondary to uncontrolled seizures, to adverse effects of antiepileptic drugs (AEDs) or to the underlying biological abnormality. The choice of an adequate AED with an appropriate dose regimen may lead to a favorable outcome. This feature is especially relevant in elderly patients with dementia and associated epilepsy, a vulnerable population in which the diagnosis of seizures can be difficult and for whom treatment guidelines are not yet available. Based on available information and on data derived from studies with other populations, recommendations for the management of these patients are presented.

Functional psychiatric disorders are associated with a variety of cognitive deficits and, in some instances, severe cognitive impairment. This paper reviews the cognitive profile of patients with schizophrenia, depression, bipolar and anxiety disorders, as well as the longitudinal course and clinical outcome of the cognitive impairment associated with these conditions. The paper also discusses some of the mechanisms that may contribute to the expression of the cognitive deficits in these disorders and their potential relationship with common causes of dementia.

There is much caregiving literature describing factors that affect carer burden, and interventions that may be useful for carers of those with common dementias such as Alzheimer's disease (AD). By contrast, relatively little information and few data are available on potentially diverse issues facing carers of those with uncommon dementias, such as frontotemporal dementia (FTD), Huntington's disease (HD) and human immunodeficiency virus (HIV) dementia. This paper highlights particular characteristics of caregiving for those with uncommon dementias, and the unique needs that may arise for this group of carers who often “fall between the net” of services and supports available. Further research into this area is required.