Causes of Dementia

There are many causes of dementia. They can be classified into the following groups  

Degenerative Dementias. Far and away, the most common dementias in the United States are of the degenerative type. These result from gradual deterioration of the brain and include Alzheimer s disease (AD). AD accounts for about 60% of dementias. Vascular dementia, another degenerative dementia, is the second most common form and accounts for another 10%. 

The cause of Alzheimer s disease is unknown, but genetic factors clearly play a role. One clue supporting this view is provided by the observation that individuals with Down syndrome, a common cause of mental retardation, frequently develop a dementia similar to Alzheimer s disease during early adulthood. Vascular dementia, which is also called multi-infarct dementia, results from the accumulation of tiny strokes. Individually, these strokes or infarcts are too small to cause any noticeable problem, but as they accumulate, they produce deficits similar to Alzheimer s disease. Other neurological diseases such as Parkinson s disease, Pick s disease, and Huntington s disease cause slow deterioration of the brain that ultimately leads to a degenerative dementia. 

Infectious Dementias. One hundred years ago, the most common cause of dementia was an infection syphilis. Today, syphilis is well treated and seldom left to linger long enough to infect the brain and cause dementia, but a blood test for syphilis remains a routine part of the assessment for patients newly diagnosed with dementia. Today, the most common infectious cause of dementia is HIV/AIDS. Other, rare forms of infection-caused dementia include Creutzfeld-Jakob disease (spongiform encephalopathy) and subacute sclerosing panencephalitis (SSPE), the latter caused by the measles virus in unvaccinated children. 

Substance-Induced Dementias. Substances of abuse can also cause dementia. The most common is alcohol-related dementia. Chronic alcoholism leads to dementia in several ways. The poor diet of the alcoholic causes a deficiency of certain essential nutrients such as thiamine. The alcoholic often suffers recurrent head injuries from falls or altercations. Alcohol-induced liver failure can expose the brain to toxic injury. Finally, the direct toxic effects of alcohol itself on the brain can lead to dementia. In addition to alcohol, the abuse of inhalants such as paint thinner and 

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Dementia with Lewy bodies (DLB) is considered the second most common cause of dementia after AD. The disorder is characterized by progressive fluctuating cognitive impairment, visual hallucinations and motor features of Parkinsonism. Neocoitical cholinergic activity is more severely depleted in DLB than in AD, and DLB also affects the caudate nucleus, the thalamus and the brain stem. Tolerability of ChEI in DLB appears similar to AD, with some gastrointestinal effects and muscle cramps. 

A diagnosis can be made only at autopsy therefore the diagnosis is established following an extensive history and physical examination, and by ruling out other potential causes of dementia. 

Tests to exclude possible causes of dementia include a depression screen, vitamin B12 deficiency, thyroid function tests [thyroid-stimulating hormone (TSH) and free triiodothyronine and thyroxine], complete blood cell count, and chemistry panel.21... 

Alzheimer s disease (AD) is the most frequent cause of dementia (50-70%), followed by vascular dementia (30 0%) and mixed dementia (15-20%). These prevalent forms of age-related neurodegeneration represent a major problem of health in developed countries, with more than 25 million people affected and probably more than 75 million people at risk during the next 20-25 years worldwide. The prevalence of dementia increases exponentially, from approx. 1% at 60-65 yr to more than 30-35% in people older than 80yr. It is very likely that in those patients older than 75-80 yr most cases of dementia are mixed in nature (degenerative plus vascular), whereas pure AD cases are very rare after 80yr (1-3). 

Too Little Neurotransmission. In some cases, disease appears to damage or cause the death of nerve cells, a process called neurodegeneration. These diseases cause problems by stopping normal neurotransmission altogether. One example of this disease process is Alzheimer s disease, the major cause of dementia in the elderly. In this common and devastating illness, acetylcholine-containing nerve cells, and others, die prematurely. 

Despite these clues, a definitive diagnosis often cannot be made. In that case, a prudent course is to treat what would be treatable. The initial evaluation should carefully look for treatable medical causes of dementia or depression. These include vitamin deficiency and hypothyroidism among others. If no medical causes are found, then treatment for depression should be started. If the patient is depressed and suffering from a pseudodementia, the patient can expect full recovery of memory as the depression resolves. But if the patient has a progressive dementia such as Alzheimer s disease, then treatment for depression has done no harm and may still provide some benefit. 

The overall rate of dementia in persons over 65 years of age is 5-10%. As many as 4 million people in the United States suffer from dementia, and these numbers will undoubtedly rise as the population ages. In fact, dementia increases exponentially with age—the rate doubling every 5 years from age 65 to age 90. By the year 2050, we believe that more than 10 million Americans will have Alzheimer s disease, the leading cause of dementia. 

Table 10.1 shows the proposed risk factors for Alzheimer s disease, the most common cause of dementia. Heading this list is of course old age. But be careful how you... 

The course of illness depends on the cause of dementia. As a rule, the degenerative dementias are slowly progressive, taking several years to run their course from initial diagnosis to death. Vascular dementia, like other degenerative dementias, is slowly progressive but in a stepwise fashion. A patient with vascular dementia will function at a particular plateau until another small infarct causes a small but noticeable and sudden decline. 

Dementia reversal represents attempts to treat the underlying cause of the so-called reversible dementias. Although only a few causes of dementia are to any... 

Since that time, we ve found that some causes of dementia can be treated. In addition, other treatable conditions as noted earlier cause cognitive impairment that resembles dementia (pseudodementia). Treatment aimed at dementia reversal depends on a careful assessment to identify those patients who have these potentially reversible conditions. 

TABLE 10.4. Potentially Treatable Causes of Dementia or Pseudodementia... 

C F]Fluoro-2-deoxy-D-glucose ([ F]FDG) is the most commonly used PET radiopharmaceutical, and it has also proven to be valuable in the early detection of AD and in the differentiation of AD from other causes of dementia. F-Labeled radiopharmaceuticals have also successfully been used to study various components of the serotonergic brain... 

Bowden CL, Brugger AM, Swann AC, et al Efficacy of divalproex vs lithium and placebo in the treatment of mania. JAMA 271 918-924, 1994b Bowen DM, Davison AN Biochemical studies of nerve cells and energy metabolism in Alzheimer s disease. Br Med Bull 42 75-80, 1986 Bowen DM, Smith CB, White P Accelerated ageing or selective neuronal loss as an important cause of dementia Lancet 1 11-14, 1979 Bowen DM, Smith CB, White P, et al Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer s disease. J Neuro-chem 41 266-272, 1983... 

It is progressive neurodegenerative disorder and mainly affects older individuals. It is the most common cause of dementia which is a impairment of intellect, memory and personality in the absence of gross clouding of motor involvement. 

A large number of epidemiology and case-control studies have examined the potential association between oral aluminum exposure and Alzheimer s disease. A number of these studies have been criticized for flawed patient selection, poor comparability of exposed and control groups, poor exposure assessment, poor assessment of health outcomes, and weak statistical correlations (Nieboer et al. 1995 Schupf et al. 1989). Studies conducted by Martyn et al. (1989), McLachlan et al. (1996), and Michel et al. (1990) have found an association between oral exposure to aluminum and an increased risk of Alzheimer s disease. In a survey study conducted by Martyn et al. (1989), the incidence of Alzheimer s disease in individuals under the age of 70 was estimated from computerized tomographic (CT) records. The 1,203 subjects lived in 88 county districts within England and Wales. Data on aluminum concentrations in the municipal water over a 10-year period were obtained from water authorities and water companies. The subjects were classified as having probable Alzheimer s disease, possible Alzheimer s disease, other causes of dementia, or epilepsy. The relative risks of Alzheimer s disease were elevated in the subjects living in districts with aluminum water concentrations of >0.01 mg/L. However, the relative risk exceeded unity only in the subjects with aluminum water concentrations of >0.11 mg/L (relative risk of 1.5, 95% confidence interval of 1.1-2.2). 

Dementias cause a loss of previously normal intellectual functions (in mental retardation such functions are not attained). Major causes of dementia are Alzheimer s disease and multiple strokes or infarcts. 

There is no blood test or X-ray to diagnose Alzheimer s-type dementia per se, but there are tests for causes of dementia syndromes that may at first look like Alzheimer s disease, and often those causes are treatable. 

TABLE 6.2. Causes of Dementias That Are Reversible or Treatable... 

Abstract Alzheimer s disease (AD) is the most common cause of dementia in the elderly and is characterized by senile plaques, neurofibrillary tangles, synapse loss, and progressive neuronal deficits. There is an abundance of evidence suggesting that oxidative stress is involved in the pathogenesis of Alzheimer s disease. Several investigations have revealed the presence of oxidation products of proteins, lipids, and DNA in postmortem tissue from AD patients, indices that are indicative of increased oxidative stress. In the present review we discuss the role of protein oxidation in the brain of subjects with AD and MCI. 

In addition, other possible causes of dementia also need to be excluded, especially the treatable forms of cognitive impairment, such as that due to depression, chronic drug intoxication, chronic central nervous system infection, thyroid disease, vitamin deficiencies (i.e.. Bn and thiamine), central nervous system angitis, and normal-pressure hydrocephalus (Bird, 2008). Individuals who do not meet these criteria but have short-term memory loss and have only minimal impairment in other cognitive abilities and are not functionally impaired at work or at home are considered to have mild cognitive impairment (Petersen et al., 2001). 

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