Dementia

Dementia is not a normal part of aging and is characterized by chronic, progressive, and often irreversible memory loss. Dementia affects three domains: cognition, function, and behavior. Cognitive impairment can affect executive function, short-term memory, and language ability (both expressive and received). Behavior can be affected by auditory or visual hallucinations, delusions, depression, and anxiety as co-morbidities with dementia. Functional status is affected due to ADL and IADL impairment or dependence as well as potential caregiver burden. Patients with dementia are typically unaware that they have a memory problem and will often deny this when asked.

Important questions to ask a patient (or caregiver) when presenting with a concern of memory loss include:

• What is the baseline mental status?
• What is the baseline (ADL/IADL) functional status?
• Does the patient feel they have a problem with their memory?
• Any depression symptoms?
• Any recent medication changes? (New or stopped?)
• Any history or recent drug or alcohol use?
• Any history of brain injury, stroke, seizure, or sleep apnea?
• Any changes in ambulation ability?

As part of the physical exam, in addition to heart, lungs, and abdomen assessments, one should also evaluate cognitive assessment using the MOCA instrument as well as a detailed neurological exam including described in Chapter 4 (included here for convenience):

Nervous (central and peripheral) system:

• Cranial nerves: assess each level vs. gross function
• Muscle strength of upper and lower extremities
• Deep tendon reflexes of upper and lower extremity of biceps, brachialis, triceps, patellar, Achilles reflexes
• Coordination:
  • Finger-to-nose
  • Heel-to-shin
  • Tandem walking (i.e. heel-to-toe)
• Timed get up and go test
• Cognitive testing: MOCA (or part of it, i.e. digit span)

As described previously, the timed get up and go test is used to assess a person's mobility and requires both static and dynamic balance. It uses the time that a person takes to rise from a chair without assistance, walk three meters, turn around, walk back to the chair, and sit down. If the total time to perform this time is less than 10 seconds, the risk of falling in this patient is considered low. If the time is between 10-20 seconds, the risk of falling is intermediate. If the time required is greater than 20 seconds, the patient is at a high risk of falling. The usefulness of the timed get up and go test is to assess a patient with memory loss for normal pressure hydrocephalus; these patients present with memory loss, impaired gait, and urinary incontinence. This will be discussed in more detail shortly.

Workup for dementia should include cognitive assessment (i.e. MOCA), laboratory studies to rule out reversible causes of dementia (such as B12, folate, TSH, and RPR), as well as CT or MRI of the brain. In addition, neuropsychological testing (performed by a neuropsychologist) is useful to further determine the neurocognitive deficits a patient may be experiencing or developing.

Six causes of dementia among geriatric patients include:

1. Alzheimer’s disease (ca. 60%-70% of cases)
2. Vascular dementia (ca. 20%-30% of cases)
3. Normal pressure hydrocephalus
4. Lewy body dementia
5. Parkinson’s disease dementia
6. Frontotemporal dementia

Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common cause of dementia (>50%) among persons aged 65 and older. Prevalence of Alzheimer’s disease is approximately 3-4 millions people globally, with a triplicate increase in incidence each decade above 65. The onset is often insidious and not recognized until patients are in the moderate stages of the disease.

Risk factors for Alzheimer’s disease include patients over the age of 65, female sex, low education, Down syndrome (trisomy 21, produces excessive amyloid), low socioeconomic status, family history of Alzheimer’s disease, cardiovascular disease (i.e. hypertension and hyperlipidemia), and head trauma. Genetic factors include apolipoprotein E4 gene expression, mutations in amyloid precursor proteins resulting in the production of excess amyloid, trisomy 21 (as amyloid is produced by chromosome 21), and mutations in the genes that produce amyloid precursor protein (the presenilins).

Neuropathologic findings include brain atrophy, beta amyloid plaques/tangles, tau protein deposition, an inflammatory response in the brain to the presence of disruptive beta amyloid plaques/tangles, and a deficiency in acetylcholine. Summarizing, the mechanism of disease is due to extra-cellular beta-amyloid deposition.

From the pathophysiology, pharmacologic approaches are tailored and include acetylcholine esterase inhibitors including donepezil, rivastigmine, and galantamine as well as NMDA-receptor antagonists such as memantine; utilization of donepezil and memantine has a synergistic effect. It should be noted that these medications delay progression but do not stop it and are only appropriate for mild-to-moderate disease. Common side effects of donepezil include bradycardia and GI bleeds. Non-pharmacologic treatment measures include maximizing function, maintaining adequate nutritional status, disimpaction of cerumen, wearing glasses and hearing aids, and to encourage physical activity as well as intellectual stimulation. Treatment plans should be developed using an interdisciplinary approach and involve the family and caregivers as well as the patient in its development.

Alzheimer’s disease is a clinical diagnosis, as a definitive diagnosis requires autopsy and sampling of brain tissue to identify the features listed above. Clinical signs and symptoms/typical behaviors: amnestic memory deficit (short term memory shows worse decline than long term memory), progressive aphasia/word finding difficulty, visuo-spatial disturbances (such as being unable to draw a cube or interlocking pentagons on cognitive assessment exams), and executive function deficits (reckless spending, for example). Symptoms will progressively worsen and patients may not be aware of them. Patients or family members may anecdotally provide accounts of concerning behaviors including getting lost while driving in familiar areas or being unable to operate television remotes or other devices which have been extensively used by patients.

Vascular Dementia

Vascular dementia (abbreviated VD; often interchangeably used with multi-infarct dementia) arises as a result of decreased cerebral blood flow. This is a direct result of trauma or medical disease, including hypertension, hyperlipidemia, cerebrovascular disease with history of transient ischemic attacks or cerebrovascular accidents (i.e. strokes), or atrial fibrillation, among others. A stroke may be precipitated by atrial fibrillation due to the formation of a thrombus from the irregular beating of the atria leading to coagulation that ultimately makes its way to the cerebral circulation. As the net result of these pathologic processes often results in brain damage, a co-morbid seizure disorder is not uncommon. Summarizing, the mechanism of disease is decreased cerebral blood flow. Unlike Alzheimer’s disease, there is not an associated acetylcholine deficiency or the presence of extra-cellular protein deposition. The goal of treating vascular dementia is to prevent further cardiovascular disease progression. Medications can include a statin (to decrease low-density lipoprotein (LDL) cholesterol), clopidogrel (an anti-platelet aggregator), anticoagulation (to prevent thrombus formation), and other means of preventing further cerebral infarcts from occurring. Clinical presentation and extent of memory loss depend on the severity of underlying diseases and the parts of the brain that are affected.

Normal Pressure Hydrocephalus

Normal pressure hydrocephalus (NPH) occurs due to the abnormal buildup of cerebrospinal fluid (CSF) in the lateral ventricles of the brain due to obstruction of CSF flow, causing the ventricles to enlarge and pressure to be put on the brain. Symptoms associated with normal pressure hydrocephalus include cognitive impairment (i.e. dementia), shuffling or “wobbly” gait, and urinary incontinence. The mnemonic “wet, wacky, and wobbly” is often used to describe the symptoms of normal pressure hydrocephalus. Diagnosis is made either using CT of the head or MRI of the brain. Both will show enlargement of the lateral ventricles in the brain. Treatment of normal pressure hydrocephalus involves the surgical placement of a ventriculoperitoneal shunt (a VP shunt) that facilitates drainage of the cerebrospinal fluid into the abdomen. Upon return of the ventricles to normal size, many of the symptoms of normal pressure hydrocephalus resolve. However, if not treated for long periods of time, symptoms may worsen and be irreversible. With early diagnosis and treatment, most symptoms resolve and the patient will return to their prior baseline functional and cognitive status.

Lewy Body Dementia and Parkinson’s Disease Dementia

Parkinson’s disease is clinically identified by the presence of symptoms including micrographia (small handwriting), cogwheel rigidity with joint movement (most easily appreciated by assessing pronation and supination and monitoring the radial head), resting tremor, and a short-stepped shuffling gait. First line treatment should involve initiation of carbidopa/levodopa to replete central nervous system dopamine.

In Lewy body dementia, cognitive impairment is a presenting feature at the time of diagnosis of Parkinson’s disease. In Parkinson’s disease dementia, cognitive impairment typically occurs in the last half of the Parkinson’s disease clinical course. Hallucinations are a hallmark feature of Lewy body dementia. Rivastigmine is indicated for Parkinson’s disease-related dementias.

Frontotemporal Dementia

Frontotemporal dementia (FTD) is a collective term for disorders that affect the frontal and temporal lobes of the brain. These areas are associated with executive function (such as personality and behavior; frontal lobe) and language (temporal lobe). The mechanism of disease involves portions of these lobes which undergo atrophy. Signs and symptoms vary, depending upon the portion of the brain affected. Frontotemporal dementia causes dramatic changes in personality and patients are observed to become socially inappropriate (cursing and making sexually inappropriate remarks), impulsive, or emotionally indifferent. Others lose the ability to use language. Though characteristics of the clinical presentation often overlap those of Alzheimer’s disease, the age of onset is much sooner (i.e. fifth decade of life for FTD versus seventh decade for AD). Pick’s disease is a subtype of FTD.

Behavior Disturbances in Dementia

Behavioral disturbances are common and prominent characteristics of dementia and occur in anywhere between 30-90% of patients. Behavior disturbances include depression, anxiety, psychosis, agitation, aggression, disinhibition, and sleep disturbances. Any use of antipsychotics for agitation in patients with Alzheimer’s disease is considered off-label and also carry black box warnings for risk of increased mortality. Behavior changes from a patient’s baseline are often due to an underlying physical (not mental) illness and may be due to underlying infection leading to superimposed delirium. Delirium will be discussed in more detail in Chapter 6. Clozapine is indicated for Parkinson’s patients with psychosis and agitation in the setting of Lewy body dementia but its use is restricted due to the need for weekly CBC monitoring for agranulocytosis. Physical restraints should be avoided as they can cause physical deconditioning and muscle weakness.

Review Questions

Questions 1-5: A 75-year-old female presents to her primary care physician’s office for evaluation of worsening memory. She was brought to the office by her son, who notes that her memory has continued to progressively decline over the last several months. Her medical history is notable for hypertension, atrial fibrillation, hyperlipidemia, two transient ischemic attacks, and osteoporosis. She is a daily tobacco smoker and has a 50-pack year history. She follows regularly with her primary care physician, but lives alone, and her son reports that she is not compliant with taking her medications as directed. She last saw her primary care physician six months ago as directed. On physical examination, her vital signs are found to be unremarkable, but her heart rate is noted to be irregular. She has no recorded history of falls. Her laboratory studies are unremarkable. Her medications include atorvastatin, metoprolol tartrate, alendronate, lisinopril, and hydrochlorothiazide.

1. What is the most likely diagnosis of her cognitive impairment?

A. Alzheimer’s disease
B. Vascular dementia
C. Lewy body dementia
D. Frontotemporal dementia
E. Acute delirium

2. What is the mechanism of disease in this patient?

A. Infection
B. Ischemia
C. Infarction
D. Normal age-related changes in cognition

3. What dementia-delaying medication is most appropriate for this patient?

A. donepezil
B. memantine
C. galantamine
D. rivastigmine
E. There are no dementia-delaying medications indicated for this patient.

4. What medication could she most benefit from slowing further progression of her cognitive impairment?

A. rivaroxaban
B. escitalopram
C. bupropion
D. amlodipine
E. No additional medication

5. Which of the following diagnostic modalities would be useful in diagnosing her cognitive impairment?

A. 2D echocardiogram
B. CT of the head without contrast
C. Carotid ultrasound
D. X-ray of the cervical spine
E. None of the above

6. Which of the following blood tests should be ordered to rule out reversible causes of dementia?

A. B12 level, folate level, thyroid stimulating hormone, rapid plasma reagin (RPR)
B. complete blood count, basic metabolic panel, lipid panel, hemoglobin A1c
C. B12 level, folate level, thyroid stimulating hormone, hemoglobin A1c
D. complete blood count, thyroid stimulating hormone, rapid plasma reagin, lipid panel
E. basic metabolic panel, lipid panel, hemoglobin A1c, B12, folate

7. Which of the following medications is the most appropriate for psychosis and agitation in a Parkinson’s disease patient with Lewy body dementia?
A. clozapine
B. quetiapine
C. haloperidol
D. aripiprazole
E. ziprasidone

8. When are physical restraints an acceptable treatment for agitation?

A. Physical restraints should be used when the resident is at an increased risk of falls.
B. Physical restraints should be used when the resident has wandering behaviors.
C. Physical restraints should be used at the discretion of the nursing staff.
D. Physical restraints should be avoided as they can cause physical deconditioning and muscle weakness.
E. Physical restraints should be used in addition to bed rails because when both are used together it is more effective than using either on its own.

9. Which of the following is a side effect of donepezil?

A. constipation
B. bradycardia
C. tachycardia
D. weight gain
E. polycythemia

10. Which medication is often combined with memantine due to a synergistic effect?

A. galantamine
B. rivastigmine
C. atorvastatin
D. donepezil
E. lisinopril

11. Which of the following medications is indicated for the treatment of agitation in patients with Alzheimer’s disease?

A. risperidone
B. quetiapine
C. haloperidol
D. lorazepam
E. None of the above are indicated for the treatment of agitation in patients with Alzheimer’s disease

Answers to Review Questions

1. B
2. C
3. E
4. A
5. B
6. A
7. A
8. D
9. B
10. D
11. E