DEMENTIA

DEMENTIA:

A 67-year-old woman is brought to the clinic complaining of forgetfulness. She states that recently she has been forgetting common phone numbers and the name of her mailman, whom she has known for 25 years. Her past medical history is significant for hypertension, coronary artery disease, and high cholesterol. Her physical examination is unremarkable.

Definition. Cognitive function is measured by various mental functions, including mem- ory, concentration, language, praxis, visuospatial functioning, and executive functions. “Dementia” refers to loss of memory with impairment of any other cognitive function suf- ficient to interfere with social or occupational functioning.

Etiology. There are more than 100 identifiable causes of dementia in the elderly. Among the many reversible causes of dementia, you should consider hypothyroidism, vitamin B12 defi- ciency, hepatic or uremic encephalopathy, CNS vasculitis, syphilis, brain abscess, brain tumor

(primary or metastatic), medications (especially anticholinergics), obstructive sleep apnea, central sleep apnea, trauma, subdural hematoma, normal pressure hydrocephalus (NPH), and depression. Irreversible causes of dementia include progressive multifocal leukoencephalopa- thy, Alzheimer disease, dementia with Lewy bodies, frontotemporal degeneration including Pick disease, vascular dementia including multi-infarct dementia and Binswanger disease, and Creutzfeldt-Jakob disease (CJD). Alzheimer disease accounts for 60 to 80% of all causes.

The prevalence of dementia is 1–5% between ages 65–69, rising to 45% by age 100. Only 5% of Alzheimer disease is inherited.

Clinical Presentation. The most common cause of dementia is Alzheimer disease. Typically, patients will present with problems in memory and visuospatial abilities that generally occur early in the course of the disease. Social graces can be retained despite significant loss of cognitive decline. Hallucinations and personality changes typically occur late in the course of the disease.

Mild cognitive impairment refers to memory loss without dysfunction of other cognitive domains. These patients have a higher risk of developing Alzheimer disease later in life but do not have Alzheimer disease. The rate of progression is 15–20% per year.

Alzheimer disease is, by definition, the loss of memory as well as other cognitive disturbances, such as aphasia, agnosia (the failure to identify entities despite intact sensory function), apraxia, or the loss of the ability to make plans and execute them. There is no single diagnostic test for Alzheimer disease.

Patients with frontotemporal dementias such as Pick disease will typically present with per- sonality changes early in the course of their disease, with relative sparing of their visuospatial function. Social, interpersonal, and emotional abnormalities precede memory impairment. Frontotemporal dementia is often noted primarily by the family because the patient lacks insight into their condition. There is no proven therapy for this condition.

Dementia with Lewy bodies (DLB) can be confused with delirium and is characterized by

fluctuating cognitive impairment.

Dementia secondary to Parkinson disease should be accompanied by clinical findings consis- tent with that disease. Recurrent visual hallucinations are also characteristic.

Dementia secondary to CJD is characterized by a shorter (weeks to months), more aggressive course than Alzheimer disease. Patients with CJD will present with dementia and myoclonus. Variant CJD is bovine spongiform encephalopathy (BSE). BSE is from the ingestion of prions from affected cattle. The diagnosis of CJD is by rapidly progressive dementia, myoclonus, ataxia, and the presence of 14-3-3 protein in the CSF. EEG may also help diagnose. These criteria can eliminate the need for brain biopsy.

Vascular dementia is divided into multi-infarct dementia, which typically has a stepwise pro- gression associated with discrete cerebrovascular events, and Binswanger disease, involving the subcortical white matter, which presents with a slowly progressive course.

Normal pressure hydrocephalus will present with prominent gait abnormalities early in the course of the disease that usually precede the onset of cognitive impairment. There will also be associated urinary incontinence.

Diagnosis. All patients with cognitive impairment should be assessed with a Mini Mental Status Examination (MMSE) to identify the areas of cognitive impairment.

Initially, the workup should focus on ruling out reversible causes of the dementia. If a revers- ible cause is identified, it should be treated, with the hope that cognitive function can be recovered. Laboratory studies should include a complete blood count (CBC), electrolytes, calcium, creatinine, liver function studies, glucose, thyroid-stimulating hormone (TSH), vitamin B12, RPR, and HIV.

Brain imaging is most useful for patients who have a focal neurologic exam, seizures, gait abnormalities, and an acute or subacute onset of their symptoms. EEG and CSF evaluation are not necessary except for NPH-opening pressure. No CSF marker is proven beneficial with the exception of 14-3-3 protein in CJD.

Treatment. Treatment of dementia revolves around insuring that the family and the patient have the proper medical and emotional support to cope with the disease. Caregivers are at an increased risk for depression and anxiety. Their concerns and frustrations should be addressed at frequent intervals.

Raising the level of acetylcholine in CSF benefits patients with Alzheimer disease. Pharmacotherapy with donepezil has been shown to improve cognitive function in mild to moderate dementia. Other anticholinesterase inhibitors (rivastigmine, galantamine) appear  to have similar efficacy.

Memantine is a disease-modifying drug used in advanced disease either alone or with a cholinesterase inhibitor. Memantine seems to be neuroprotective and reduces the rate of progression of disease.