Vascular dementia is defined as the dementia resulting from ischemic, ischemic-hypoxic, or hemorrhagic brain lesions due to cerebrovascular or cardiovascular pathology. Clinical findings in vascular dementia are heterogeneous and depend to a great extent on the speed, total volume, and localization of the lesions. Typically, the onset is in later life, and the dementia syndrome is the result of small brain infarcts, which lead to cognitive deterioration when they have enough cumulative effects on critical areas of the brain. However, cognitive impairment and probably dementia also can be seen in chronic ischemia without frank infarction. Acute onset usually develops after stroke, either from thrombosis, from an embolism, or rarely from a single massive hemorrhage. Onset and course of dementia are often more gradual in so-called multi-infarct dementia, as a consequence of many minor ischemic episodes, which produce an accumulation of lacunae in the cerebral parenchyma.
Cortical dementia occurs when the infarcts affect primarily the cortex, with focal neurological signs being the norm. Subcortical dementia is typically seen in patients with a history of hypertension and foci of ischemic destruction in the deep white matter of the cerebral hemispheres. A variant of vascular dementia is Binswanger’s disease, or subcortical arteriosclerotic encephalopathy, which is associated with pseudobulbar palsy, spasticity, and weakness. In such cases, extensive, diffuse demyelination of white matter can be seen in peri-ventricular regions, and recent neuroimaging techniques have shown that the condition is more frequent than previously suspected. Mixed cortical and subcortical syndromes are also common in vascular dementia, with neuroimaging findings or autopsy findings suggesting the presence of lesions in both cerebral areas. Mild cognitive impairment of the vascular type also has been described, with an outcome worse than in nonvascular mild cognitive impairment.
The course of vascular dementia has classically been described as stepwise and patchy, but advances in brain imaging techniques have shown that patients with vascular dementia may have clinical courses as gradual and smooth as in patients with DAT. Poststroke depression, independent of the disability caused by the disease, is frequent. Emotional lability, with transient depressive mood, weeping, or explosive laughter, is also a classic finding in these patients. Personality is usually relatively preserved, but in a proportion of patients, personality changes may be evident, with apathy or disinhibition or the accentuation of previous traits such as egocentricity, paranoid attitude, or irritability.
Most studies have supported the view that the total volume of infarcted brain and the total number of infarctions with additive or multiplicative effects correlate well with the severity of dementia. However, the location of the infarctions also may be important. In more than two-thirds of vascular dementia patients, the pathological correlate is the lacunar state, characterized by multiple lacunar infarctions in subcortical structures such as the basal ganglia and thalamus. Other pathological findings include watershed infarctions due to reduction in brain perfusion, multiple embolic infarcts, diffuse demyelination of white matter in Binswanger’s disease, and a mixture of lesions. The term vascular cognitive impairment has been proposed to broaden the current definitions of vascular dementia to recognize the important part cerebrovascular disease plays in several cognitive disorders, including DAT and other degenerative dementias. It is now estimated that the prevalence of mixed cases of vascular dementia and DAT has been underestimated; that pure vascular dementia is rare; and that, in addition to simple coexistence, vascular dementia and DAT may share common pathogenetic mechanisms.
HIV-associated dementia, formerly called AIDS dementia complex, is now the most common dementia caused by an infectious disease. Cognitive deterioration is frequently observed in infection with HTV-1 and may be severe enough to fulfill criteria for dementia. Cognitive dysfunction may be the earliest or the only clinical manifestation of AIDS. The heterogeneity of psychopathological manifestations and the occurrence of both cortical and subcortical features suggest disseminated brain pathology in this condition. Noncognitive psychopathology — in particular depressive syndromes associated with the subcortical cognitive psychopathology — is also common in patients infected with HTV-1.
Creutzfeldt-Jakob disease is a dementia with an extremely rapid course, caused by a transmissible infectious agent, the prion. Cognitive deterioration is progressive, widespread, very severe, and accompanied by pyramidal and extrapyramidal signs, early characteristic myoclonic jerks, muscle rigidity, and ataxia. Death usually occurs in 6-12 months. Pathological findings are widespread in both the cortex and the subcortical structures. Spongiform change in neurons is characteristic, and neuronal loss and astrocytic proliferation occur.
Neurosyphilis may evolve into different types of dementia if left untreated. The most severe form is general paresis, which becomes evident 15-20 years after the original infection. The dementia may be easily recognized in the advanced state and is accompanied by characteristic signs, such as pupillary abnormalities, dysarthria, tremor of the tongue, and hypotonia. However, the onset is commonly insidious, and the diagnosis may be suggested when the initial memory difficulties are accompanied by indifference, facial quivering, tremor, and, sometimes, myoclonus. Intellectual deterioration is progressive and severe, with cortical deficits and often signs suggesting frontal lobe involvement, including disinhibited behavior. Psychotic phenomena, such as grandiose or hypochondriacal delusions, are common.
Chronic meningitis, caused by chronic bacterial, parasitic, or fungal infections, can eventually cause progressive dementia, with fluctuations in arousal and cognitive performance, apathy and lethargy, disorientation, and cranial nerve abnormalities.
Immunosuppressed or debilitated, chronically ill patients are at special risk. Herpes simplex encephalitis may cause major neurological and cognitive sequelae. Because herpes encephalitis has a predilection for the temporal lobes, amnestic and aphasic syndromes are common, but dementia also can be seen. Other cortical signs reflect damage to other cortical areas.
Progressive multifocal leukoencephalopathy (PML) is a rare complication of a common subacute viral disorder, most commonly seen in immunosuppressed patients. Clinical signs and symptoms are quite heterogeneous, and the dementia may include both cortical and subcortical signs and symptoms, reflecting widespread lesions in the central nervous system. PML is usually progressive, with motor dysfunction and blindness sometimes developing; death commonly follows in a few months.
Metabolic and Toxic Dementias
Metabolic and toxic dementias form a heterogeneous group of diseases (see Table 3) of special interest to the consultant psychiatrist because they are relatively frequent in medical settings and are potentially reversible. Dementia in these conditions has predominantly subcortical features but may have mixed characteristics. Psychomotor slowing may be severe in cases of hy-pothyroidism. Memory deficits are often accompanied by problems in executive function, with impaired attention and concentration also common. Whether the metabolic and toxic encephalopathies are best conceptualized as reversible dementias or as chronic deliria is unclear, and perhaps the distinction is primarily semantic, particularly in cases of hepatic, renal, and cardiopulmonary failure. Progression of the dementia is usually quite insidious, in relation to the chronicity of the metabolic or toxic condition, and the course tends to be disease-specific.
The neuropathology in these conditions is not well known. Hippocampal neurons are probably most vulnerable to anoxic injury but are also vulnerable to severe hypercholesterolemia and to repeated or severe episodes of hypoglycemia, such as may occur in type 1 diabetes mellitus. Hypothyroidism can produce subcortical damage through a mechanism of relative cerebral hypoxia. Vitamin B12 deficiency, as seen in pernicious anemia, has been associated with disseminated degeneration in areas of cortical white matter, the optic tracts, and the cerebellar peduncles. In pellagra, lack of nicotinic acid and probably other vitamin B deficiencies may lead to neuronal destruction.
Alcoholic dementia, one possible complication of chronic alcoholism, is more frequent after age 50 years and is likely multifactorial in etiology. Thiamine and other vitamin B deficiencies and multiple TBIs have been found in these patients. Pathological findings at autopsy suggest that this condition is probably underdiagnosed. The cognitive deficits are more global here than in pure amnestic syndrome (e.g., Korsakoff’s psychosis), and unlike those patients, alcoholic patients with dementia may complain of decreased efficiency of memory and intellectual functioning. Deterioration of visuoperceptual and executive functions is commonly found. Neuropatholog-ical changes include cortical atrophy and nerve fiber disintegration with dissolution of myelin sheaths. Dementing syndromes are also seen in distinct brain diseases related to chronic alcoholism, such as Marchiafava-Bignami disease, with degeneration of the corpus callosum and anterior commissure, or in acquired hepatocerebral degeneration.
Dementing syndromes also may occur in chronic intoxication with medications, which can be either prescribed or abused by patients. The onset is insidious, and the course is progressive; physicians should be alert to the possibility of this reversible dementia. Benzodiazepines, including those with high potency and a short half-life, are known to cause anterograde amnesia and impairment of memory consolidation and subsequent memory retrieval. Elderly patients are more vulnerable to developing the dementia syndrome. Syndromes of cognitive deterioration have been reported in cocaine users and also in heavy users of cannabis.
Neoplastic disease may affect any part of the brain and produce essentially any kind of neuropsychiatric symptoms, depending on tumor location and extent, as well as rapidity of tumor growth and propensity to cause increased intracranial pressure. Dementia is one such syndrome, and certain symptom clusters that occur with regularity may suggest the general location of lesions. Such clusters may be apparent before motor symptoms or a full dementia syndrome is suspected.
Initial symptoms of depression and some cognitive loss, with apathy, negativism, and akinesia, suggest the possibility of frontal lobe tumors such as meningioma or some forms of glioblastoma; a low performance on executive function tests further supports a frontal lobe site. Temporal lobe tumors are prone to produce seizures, and the psychiatric symptomatology may be complex and include features such as sexual disturbances, irritability, aggressiveness, and hallucinations. Tumors in the parietal region often cause characteristic language disorders when the location is in the dominant hemisphere. In the non-dominant hemisphere, they tend to produce signs such as unilateral neglect or apraxia. Tumors around the third ventricle, such as craniopharyngiomas and colloid cysts, may obstruct the flow of spinal fluid and cause hydrocephalic, subcortical dementia.
Dementia is one of the paraneoplastic syndromes that affect the brain. Limbic encephalopathy is a nonmetastatic complication of small cell lung carcinoma (and less commonly some other cancers) and may manifest with dramatic, sudden onset of memory loss. A full dementia syndrome may eventually develop. Mood disturbance, behavior change, and sometimes psychotic symptoms are also common. Pathological findings include neuronal loss, astrocytosis, lymphocytic perivascular infiltration, and glial nodules. The psychiatric symptoms may antedate the diagnosis of malignancy by several years. Early medical intervention might considerably improve the outcome of treatment in some cases.
Dementia Following Traumatic Brain Injury
A variety of cognitive difficulties are very frequent after TBI. Posttraumatic amnesia is the norm in cases of severe trauma with loss of consciousness. Cognitive deficits become permanent in more than half of the patients if they do not recover memory and orientation within 2 weeks after injury. Common difficulties include dysmnesia, organic personality disorder, dysphasia, attentional disturbances, and impairments suggestive of frontal lobe damage. Dementia also occurs and may be accompanied by seizures and neurological deficits, as well as secondary psychiatric syndromes, including depression, mania, and psychosis. Dementia in boxers (dementia pugilisticd) commonly starts with signs of ataxia, dysarthria, and Parkinson-like extrapyramidal signs before the global cognitive deficits are appreciated. Dementia due to subdural hematoma is notable because it is potentially reversible. In cases of dementia following TBI, diffuse axonal injury, with anatomic disruption and axonal tearing, has been described, and contusional foci in cortical areas and intracerebral hemorrhage also have been reported.
Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.