|Year : 2015 | Volume
| Issue : 1 | Page : 30-37
Reversible dementia in elderly: Really uncommon?
Damodar Chari, Ramjan Ali, Ravi Gupta
Department of Psychiatry, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
|Date of Web Publication||23-Jul-2015|
Dr. Ravi Gupta
Department of Psychiatry, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun - 248 016, Uttarakhand
Source of Support: None, Conflict of Interest: None
There has been a steady rise in the prevalence of dementia all over the world. Our understanding of the illness, as well as its etiopathology, has also improved. Dementias due to degenerative and vascular pathology form the most common types of dementias resulting in cognitive impairment. However, these conditions usually lead to irreversible impairment and cause significant morbidity and mortality among patients. On the other hand, there is a group of conditions among elderly, where dementia follow a reversible course provided these conditions are picked and managed early. Few common causes of reversible dementias are Vitamin B12 deficiency, normal pressure hydrocephalus, thyroid dysfunction, anticholinergic medications, depression, etc. This review will discuss all these conditions with reference to their presentation, diagnosis, and management.
Keywords: Dementia, elderly, reversible
|How to cite this article:|
Chari D, Ali R, Gupta R. Reversible dementia in elderly: Really uncommon?. J Geriatr Ment Health 2015;2:30-7
| Reversible Dementia in Elderly: Really Uncommon?|| |
Dementia is characterized by gradual decline in cognitive functioning. DSM-5 defines major neurocognitive disorder as a significant cognitive decline from previous level of functioning in one or more cognitive domains: Complex attention, executive function, learning and memory, language, perceptual motor, or social cognition. This decline should represent a significant decline in cognitive functioning along with its significant impairment and cannot be accounted for by other psychiatric conditions such as depression, other mood disorders, or psychosis.  It is considered to be an irreversible illness with a chronic debilitating course resulting in high morbidity and mortality. 
Alzheimer's dementia and Vascular dementia are two of the most common causes of dementia accounting for about 70% of total cases.  The prevalence of dementia in general of is around 23% in the 85-89 years and 40% in the 90-94 years.  However, a great number of studies state that a significant proportion of individuals suffers from dementias that are treatable. ,
What are reversible dementias?
"Reversible dementias" are conditions that may well be associated with cognitive or behavioral symptoms that can be resolved once the primary etiology is treated.  A vast number of potential causes have been identified that can result in reversible impairment of neurocognitive function in an elderly individual. There is, however, some confusion over the term "reversible dementia" as many metabolic causes of dementia have overlap with delirium [Table 1].  Moreover, cases of so called treatable dementias may be untreatable after a delay in diagnosis.  The common feature among all the possible causes of dementias for them to be called reversible is that the treatment of offending agent results in improvement in cognitive functioning. 
It is difficult to know the exact rate of occurrence of reversible dementias in the general population. This could be due the confusion regarding the terminology used to define reversible dementia as we have discussed earlier; due to the difference in population under study; or due to the presence of subclinical cases that are not readily identified.  Prevalence is highly variable, with a number of studies reporting a range between 8% and 40%. ,,,,,,,, In general, approximately 12% of patients presenting to a variety of specialist services with symptoms of dementia have treatable/reversible causes. ,
The rate of occurrence of reversible dementias varies according to the age of the population under study. Whereas they are more common among individuals younger than 60 years age, their prevalence is fairly less in older individuals aged 65 years and above. The prevalence of potentially reversible disorders has been reported 18% in patients under the age of 65 years but only 5% in those over 65 years. 
Although 5% may seem insignificant, however, it is important to know that it has implication in the overall management of patients. If these patients are not identified properly, this may lead to their faulty treatment with drugs like cholinesterase inhibitors. The side effects of these medications can add to the morbidity of patients. Furthermore, correct identification of this condition can help reduce sufferings of the patients and improve their quality of life.
Depression, Alcohol-induced cognitive impairment, normal pressure hydrocephalus (NPH), Vitamin B12 deficiency account for more than half of causes of reversible dementias. Among all causes of dementia in elderly population hypothyroidism accounted for (2.6%), B12 deficiency (1.7%), NPH (0.9%), depression (0.9%), folate deficiency (0.4%), reactive Venereal Disease Research Laboratory (0.4%), and chronic subdural hematoma ((CSH); 0.4%). 
In an Indian study, the prevalence of dementia was found to be 18% in all cases of dementias. Three most common causes identified were central nervous system (CNS) infections such as chronic meningitis, NPH, and Vitamin B12 deficiency. 
Common causes of reversible dementia
Central nervous system infection
Various CNS infections are known to cause reversible cognitive impairment, which in some cases may meet diagnostic criteria for dementia. Few of the common infectious causes of reversible dementias are chronic bacterial meningitis, neurosyphilis, chronic infections such as tuberculous meningitis or tuberculoma, Herpes encephalitis, AIDS dementia complex, and neurocystecerosis. 
Once upon a time, neurosyphilis was a major concern; however, it is usually not that prevalent these days. Neurosyphilis is an infection of brain and meninges caused by Treponema pallidum.  Neurosyphis can present in different forms, commonly as early and late syphilis. Late syphilis presents as dementia, tabes dorsalis, general paresis, sensory ataxia, and bladder/bowel disturbances.  Although cognitive impairment can be irreversible in some cases at times, mild cognitive impairment can be reversed following adequate treatment. These cases can be taken for reversible dementias. 
HIV-associated neurological condition can produce symptoms ranging from mild asymptomatic cognitive impairment to severe dementia.  These include AIDS-dementia complex, HIV encephalopathy. HIV-associated dementia may present as difficulties in concentration and memory followed by apathy, social withdrawal, and motor dysfunction.  Few studies have found that many of these conditions are reversible if treated early.  Highly active antiretroviral therapy treatment, in particular, is effective. ,
Neurocysticercosis (NCC) is one of the most common helminthic infection of CNS. It involves infestation of the cerebral parenchyma by the larval form of Taenia solium. Its usual presentations are seizure and signs of raised intracranial pressure. Racemose cysticercosis is a less frequent presentation of NCC as such they are larger, appear as multiloculated cysts and lack scolex. This is a clinically more aggressive form that can present as reversible dementia in some cases.  A study done on patients of NCC found that 15.5% of them had dementia. Of which 78.5% had a reversal of symptom 6 months following treatment of NCC. 
Normal pressure hydrocephalus
NPH is an idiopathic condition radiologically characterized by progressive ventricular dilatation with a clinical triad of ataxia, urinary incontinence, and dementia. It is usually demonstrated by raised cerebrospinal fluid (CSF) pressure, despite its name being "NPH".  One of the important feature is the dramatic improvement of symptoms following the trial of CSF removal.  The prevalence of NPH in the general population is in the range of 0.2-2.9%. However, among in individuals above 80 years, the prevalence rises to more than 5.9%. ,,
The patients of NPH usually present with impairment of attention, executive function, and memory.  Frontal and subcortical deficits such as psychomotor slowing and impaired attention, executive, and visuospatial dysfunction can be the earliest cognitive signs of NPH. A differentiating feature from Alzheimer's dementia is severe impairment of frontal lobe function while memory disturbance and orientation are relatively spared. ,,,,
Diagnosis of NPH is essentially clinical. It can be however aided by the use of specific scales and neuroimaging. , The important characteristic feature is a rapid reversal of symptoms following CSF tap. 
Treatment of NPH depends on the severity of illness. Mild to moderate cases can be treated symptomatically. However, the ventriculo-peritoneal shunt remains the treatment of choice. Various guidelines are available to decide the ideal treatment.  Older individuals who present with the full triad of symptoms are less likely to improve following CSF removal, and the condition may not be entirely reversible. 
Central nervous system tumors and space occupying lesions
There have been some reports of chronic subdural hematoma (SDH) giving rise to reversible dementia. The initial trauma to the bridging veins results in hemorrhage into the subdural space. As this vessels are very fragile in elderly even trivial trauma to them results in subdural bleed in them. Hence, it is commonly seen in elderly. The clinical presentation can vary from case to case. Usual clinical features include altered sensorium, focal neurological deficits, and memory disturbances. However, in many cases the diagnosis is often missed in early stages. , About 50% of individual reach premorbid level of functioning following surgery. 
CNS tumors in some cases can produce symptoms mimicking dementias. A case report mentions about a patient who developed reversible neuro-cognitive symptoms following intraspinal carcinoma metastasis.  Other common causes are meningiomas, metastasis, and prolactinomas. Symptom profile of these patients depends upon the site of involvement. Some cases are reversible following the surgical removal of tumors. ,
Thiamine has been known to have an important role in memory and emotion.  Deficiency of thiamine can result in Wernicke-Korsakoff Syndrome More Details is usually seen in chronic alcoholics and severely malnourished individuals. Wernicke's encephalopathy is characterized by triad of ophthalmoplegia, ataxia, and acute confusion. Korsakoff amnesia then follows with cognitive impairment in the form of retrograde and anterograde amnesia. Confabulation is a typical symptom. , Korsakoff's syndrome is difficult to treat in the majority of patients even with adequate doses of thiamine. However, early detection and treatment of Wernicke's can reverse cognitive impairment. 
Vitamin B12 deficiency is a common cause of macrocytic anemia and can result in a plethora of neuropsychiatric symptoms.  It is usually common following poor dietary intake, in pure vegetarians and in various mal-absorption syndromes such as celiac disease, gastric and ileal resections, blind loop syndrome, fish tapeworm infestation, etc.  These patients usually present with complaints of ataxia, paresthesia, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision among them.  Some studies have focused on cognitive symptoms in Vitamin B12 deficiency. According to a study, low Vitamin B12 levels are associated with neurodegenerative conditions and cognitive impairment some of which may meet criteria for dementia, as well. In a study, about 5.7% of elderly individuals in the general population were found to have low Vitamin B12 levels.  In another study, however, only 1.7% cases had reversible dementia due to cobalamin deficiency.  Hence, it is difficult to say whether Vitamin B12 is actually associated with reversible dementia or whether individuals with dementia have associated Vitamin B12 deficiency. This being said many studies have fairly established that a significant number of cases of dementia are reversible following supplementation of Vitamin B12. ,, According to a review article, treatment with Vitamin B12 and folic acid can reduce the rate of cortical atrophy and improvement in cognitive function in individuals with preexisting vitamin deficiency. 
Other vitamin deficiencies that can result in cognitive impairment in elderly are niacin and folic acid deficiency. Although there is limited evidence about the reversibility of dementias caused by them, some studies have mentioned that a folic acid replacement can improve symptoms of memory impairment. ,,
Iron deficiency is the most prevalent nutritional abnormality in the world. The common causes of iron deficiency anemia are poor intake, a chronic iron loss like in GI ulcers and malignancies, mal-absorption due to drugs such as proton pump inhibitors or due to the irritable bowel syndrome or worm infestation.  Iron deficiency has been known to cause cognitive impairment in elderly which is independent of anemia.  Iron deficiency can promote reductions in systemic and CNS concentrations of growth factors and alter expression and function of IGF-I/II and brain-derived neurotrophic factor in specific areas of the brain resulting in cognitive deficits.  Some studies have mentioned that correction of iron deficiency can reverse the cognitive impairment, but the evidence is limited. 
Patients treated with steroids can develop dementia-like cognitive symptoms that occur without the occurrence of psychosis. Dementia may be characterized by deficits in memory retention, attention, concentration, mental speed and efficiency, and occupational performance.  A case report mentions about a 70-year-old individual who presented with reversible dementia following treatment with steroids for emphysema.  The condition is rapidly reversible following tapering and omission of the drug.
Many medications in general practice have anticholinergic effects. Commonly used drugs with anticholinergic properties are antidepressants, antipsychotics, atropine, carbamazepine, first generation antihistamines, and bladder antimuscarinics, etc.  In a population based study involving 3,434 individuals above 65 years of age on treatment with drugs with anticholinergic effect about 797 participants (23.2%) developed dementia. In this, around 21% of total cases of dementia are reversible in nature.  Elderly people taking anticholinergic drugs are at increased risk for cognitive decline and dementia. Discontinuing anticholinergic treatment is associated with a decreased risk. 
Benzodiazepines (BZD) are one of the most common drugs to be prescribed for indications ranging from insomnia to anxiety and depression. BZD were considered to be safe drugs, but recent research indicates that they cause a variety of side effects in addition to obvious issues of dependence and abuse potential.  It is been found that 84% of patients attending psychiatric clinic use BZD daily for more than 6 months. BZD are known to cause variety of behavioral and neurological symptoms such as drowsiness, ataxia, confusion, dizziness, vertigo, syncope, reversible dementia, depression, impairment of intellectual, psychomotor and sexual function, psychotic symptoms, delirium, and insomnia.  Prolonged use of BZD has an adverse effect on cognition specially in the elderly population.  According to a study new use BZD is more likely to cause dementia with 50% increase in the risk.  Long-acting BZD with a half-life of 20 hours or more were also associated with higher risk than short-acting benzodiazepines. 
Various other drugs that can produce reversible dementias are valproate,  chemotherapeutic agents  Thalidomide,  although the evidence is limited.
Thyroid disorders are common in general population. Many patients with thyroid disorders may present with initial neurological complaints.  Thyroid hormones play an important role in processes involved in the development of brain such as neurogenesis, gliogenesis, myelination, synaptogenesis.  Disturbance in thyroid function has been known to cause reversible cognitive impairment.  Both low and high thyroid-stimulating hormone (TSH) levels were associated with an increased risk of developing dementia.  Hypothyroidism is one of the common causes of reversible dementia. There have been many studies, which state that hypothyroidism can result in cognitive impairment. , TSH level has been used as a standard screening test for the routine evaluation of patients with suspected dementia. In a study, it was found that even subclinical hypothyroidism can produce significant impairment of cognition in elderly individuals with TSH level as a sensitive marker. 
Similarly, even hyperthyroidism or elevated levels of thyroid hormones are known to cause dementia or increase the risk of developing Alzheimer's dementia. In a community based study, people with subclinical hyperthyroidism had significantly more likelihood to have cognitive dysfunction. Older participants with subclinical hyperthyroidism had lower Mini Mental State Examination scores than euthyroid subjects.  The exact mechanism behind this is not known. One possibility is that elevated thyroid hormones may cause oxidative damage leading to neuronal death  or due to effect on Acetylcholine metabolism. 
The chronic administration, as well as production of steroids like in Cushing's syndrome, can cause cognitive impairment. This could be due to hippocampal atrophy following hypercortisolemia.  Similarly, a recurrent episode of hypoglycemia can lead to cognitive impairment. In some cases, this may lead to dementia. 
Among other metabolic causes of reversible dementia are hypo-hyperparathyroidism, Wilson's disease, Paraneoplastic syndromes. ,
Although not entirely a true dementia, this condition is worth mentioning as many cases of depression may be mistaken for dementia. Pseudo-dementia, as it is called, occurs in patients with a history of depression. These patients usually report of memory disturbance with particular impairment of episodic memory related to personal life. There may be patchy memory loss at times. Other clinical signs of depression may be present such as low mood and lack of interest. Clinical testing may reveal memory impairment that is far less than what is reported by the patient. Treatment with antidepressants will lead to a reversal of symptoms. 
Obstructive sleep apnea (OSA) is a common clinical sleep disorder that affects cognition in few patients. This may be due to effect on attention and working memory.  It is also been suggested that OSA induced hypoxia with sympathetic vasoconstriction may produce the final effects. Patients with OSA had reduced hippocampal volume when associated with cognitive impairment. Treatment with continuous positive airway pressure produces reversibility of pathological findings in hippocampal volume. 
For proper diagnosis of a case of dementia, there is no supplement to the detailed history and clinical examination of the patient. Clinicians should have a clinical suspicion about the possibilities of reversible dementia. Any atypical case such as early age of onset, disproportionate symptoms that do not fit in a definite syndrome, the presence of a comorbid medical condition that are known to cause reversible dementia should raise the probability of reversible dementia. Clinical examination may be aided by a variety of laboratory investigations.
- Urinalysis and microscopy.
- Complete blood cell count.
- Serum electrolyte levels.
- Liver/renal function tests.
- Thyroid function tests.
- Serum Vitamin B.
- Erythrocyte sedimentation rate.
- Serologic tests for syphilis (or similar).
- Chest radiography.
- Brain imaging.
- Lumbar puncture.
- HIV screening.
- Auto antibody screening.
| Conclusions|| |
Although degenerative and vascular etiologies form a major group of dementias in elderly, quite a few of them do present with reversible causes. A great deal of clinical suspicions is needed to identify them.  Nutritional deficiencies, NPH, endocrine problems are the more common causes of reversible dementias. This being said some controversy remains whether most of condition listed as having reversible course may be actually progressive in nature. At times, patients may be misdiagnosed as having dementias when they maybe actually having delirium.  Despite this, some researchers believe that many dementias do in fact have reversal potential.  Hence, these conditions are worth knowing for neurologist and psychiatrist alike as early detection and treatment of them can improve the quality of life of patients.
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Conflicts of interest
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