In determining whether dementia is due to a general medical condition, according to the DSM-IV-TR, there must be a temporal association between the onset or exacerbation of the underlying medical condition and the cognitive impairment. The cognitive deficits must also not be solely accounted for by Alzheimer’s disease, vascular dementia, substance-induced persisting dementia, or another psychiatric illness such as major depression (e.g., pseudodementia). The DSM-IV-TR diagnostic criteria for dementia due to other general medical conditions are identical to those for other dementias (see table 1) except for Criterion C, which states that there must be evidence that cognitive deficits are etiologically related to a confirmed general medical condition other than Alzheimer’s or cerebrovascular disease. In addition, similar to the criteria for Alzheimer’s dementia, separate codes are available to specify the presence or absence of behavioral disturbance. The underlying general medical condition must also be coded on Axis III.
The presence of a separate category for dementia due to other general medical conditions represents an advance from previous criteria in that they provide the clinician with the opportunity to better delineate different etiological categories of dementia. The DSM-IV-TR specifically identifies six general medical conditions as etiological causes of dementia: HIV disease, head trauma, Parkinson’s disease, Huntington’s disease, Pick’s disease, and Creutzfeldt-Jakob disease. In addition, there is a seventh category, called dementia due to other general medical conditions, which includes various other etiologies, such as normal pressure hydrocephalus, hypothyroidism, and vitamin B12 deficiency.
Normal pressure hydrocephalus (NPH) is characterized by the clinical triad of gait disturbance, cognitive impairment, and urinary incontinence. It is a fairly rare cause of dementia, with prevalence rates that vary according to the study, clinical setting, and the diagnostic methods employed. The incidence has been estimated at 2.2 per million per year, and the prevalence has been estimated at 5000-10,000 patients in the United States. NPH typically occurs during the sixth or seventh decade of life, although it has been reported in children and young adults. Intraventricular CSF pressure increases due to impaired CSF flow, yet lumbar puncture does not reveal increased pressure. The etiology of the clinical deterioration is thought to be due to compression of small vessels by the dilated ventricles with resultant impairment in ventricular blood flow and perfusion deficits. This may be related to a reversal of CSF flow through the ependymal lining of the ventricle into the extracellular space of the white matter, as a compensitiory mechanism for an often idiopathic obstruction to normal CSF flow. Patients with normal pressure hydrocephalus have also been shown to have an increased prevalence of arterial hypertension and cerebral arteriosclerosis.
Cognitive impairments are usually characterized by memory problems, difficulty with information processing and manipulation, and generally slowed thinking. Patients tend not to demonstrate aphasia, apraxia, or agnosia, and if present, Alzheimer’s disease should be suspected. Unfortunately, the presentation of normal pressure hydrocephalus is easily confused with other dementia syndromes because ataxia and urinary incontinence can also be found in vascular dementia, Alzheimer’s disease, and Parkinson’s disease. Chronic alcohol abuse with subsequent frontal and cerebellar atrophy may also present with mental status changes (alcohol related dementia) and ataxia. The urinary incontinence is a late sign and may be due to damage to the periventricular pathways extending to the bladder control center.
Enlarged cerebral ventricles on CT or MRI that are out of proportion to cerebral atrophy and lumbar puncture are diagnostic. The treatment of normal pressure hydrocephalus is accomplished with shunt placement to reduce intraventricular pressure. Serial taps may also result in transient, but significant clinical improvement. However, dementia is less likely to improve with treatment than are the other associated symptoms. A retrospective review of patients with NPH, found that 30% of patients who underwent shunting procedures showed significant improvement. Approximately 35% of patients with shunts had surgical complications, and approximately 10% of these resulted in death or severe residual morbidity.
The prevalence of vitamin B12 deficiency has been estimated to be 15% to 44% in the elderly. Particularly in the population over 70 hypochlorhydria or achlorhydria is frequently present (in 25–50%) and leads to inadequate release of protein-bound B12. The prevalence of B12 deficiency in patients with dementia varies significantly, but the incidence of reversible B12 deficiency as the primary etiology is probably less than 1 percent. As a comorbid illness with dementia, however, B12 deficiency is a frequent finding, and several studies have documented a correlation between serum B12 levels and cognitive functioning in elderly patients. Some evidence also suggests that B12 deficiency may be more common in Alzheimer’s disease. Despite this, other studies have contradicted the correlation between dementia and serum B12 levels, and also questioned the potential reversibility of dementia with B12 replacement. One of the proposed mechanisms by which low levels of vitamin B12 may influence cognition is through the disruption of methylation reactions in the central nervous system that could increase homocysteine levels and may result in direct neurotoxic effects. Elevated homocysteine is also an independent risk factor for cerebrovascular disease and AD.
In addition to the megaloblastic hematological changes associated which may be associated with vitamin B12 deficiency, there are a several well-characterized neurological complications. The most consistently observed neurological complications are peripheral neuropathy, myelopathy, paresthesia, impaired vibratory and position sense, and symmetrical weakness. Cognitive deficits may include poor spatial copying skills, diminished episodic memory, and impaired abstract thinking. Some studies have demonstrated a worsening of cognitive functioning in dementia accompanied by B12 deficiency, and others have also shown impaired global cognition in subjects with B12 deficiency in the absence of frank dementia.
Vitamin B12 deficiency is traditionally diagnosed using serum cobalamin levels, although the additional measurement of methylmalonic acid and homocysteine is more reliable and sensitive than B12 alone. Methylmalonic acid and homocysteine are metabolites whose levels will be elevated in B12 deficiency and have been shown to fall with replacement therapy. Although pernicious anemia is not a common cause of B12 deficiency in the elderly, the schilling test may be used to evaluate the presence of intrinsic factor. The most effective treatment is parenteral substitution with cobalamin. The initial recommended dosage is 1000 micrograms daily for one week, then weekly for one month, and then monthly.
Thyroid gland dysfunction is a well-recognized cause of cognitive impairment. Hypothyroidism can lead to memory problems, psychomotor slowing, and visuoperceptual and construction deficits. Cognitive deficits in hypothyroidism may be mistaken for Parkinson’s dementia, Alzheimer’s disease, or depression (pseudodementia) because patients may be lethargic, with flattened affect, psychomotor retardation, and decreased appetite. Studies have demonstrated clinically significant impairments on the MMSE that persist even after patients return to euthyroid states with replacement therapy. Recent evidence has led researchers to question the classic categorization of hypothyroidism as a potentially reversible cause of dementia. Given the risk of potentially irreversible dementia, and because the prevalence of hypothyroidism increases with age, routine screening in the elderly is of particular importance. The relative contributions of comorbid neurodegenerative diseases in influencing cognitive decline must also be considered. Nevertheless, it seems clear that although the cognitive changes may be only partially reversible, proper treatment of hypothyroid states with replacement therapy will provide likely benefit and possibly slow or stop progressive decline.