Approach to gradual cognitive decline: Clinical sciences

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Introduction 0:00–0:30

Gradual cognitive decline refers to the slow and progressive cognitive impairment that can affect memory, behavior, personality, organizational and decision-making skills, and visuospatial awareness.
It can occur due to various neurologic conditions, including brain tumors, normal pressure hydrocephalus, Huntington disease, and different types of dementia.
Now, if a patient presents with gradual cognitive decline, you should obtain a focused history and physical exam. You should also obtain cognitive screens, such as the Montreal Cognitive Assessment or Mini-Mental State Examination.

Focused H&P, Cognitive impairment 0:30–2:57

Also, be sure to perform a depression screen because depression can sometimes present as cognitive impairment, which is also known as pseudodementia.
History typically reveals memory difficulties, like forgetting important appointments; behavior or personality changes, such as aggressiveness or impulsivity; and difficulties with organization and completing tasks, known as loss of executive function.
History might also reveal difficulty with visuospatial tasks, such as parking or using the stairs, resulting in accidents.
In addition, there might be a family history of cognitive decline. Depending on the underlying cause and the stage of the disease, the physical exam may or may not be normal.
On the flip side, the cognitive screen, which includes testing short-term memory, language, attention, and visuospatial skills, will be abnormal.
Lastly, the depression screen will be negative, but keep in mind that many patients with cognitive impairment will also have a mood disorder.
With these findings, diagnose cognitive impairment. Now, here’s a clinical pearl!
Some metabolic conditions, including hypothyroidism and vitamin B12 deficiency, can cause cognitive impairment, so the initial evaluation should also include labs, like thyroid stimulating hormone and vitamin B12 levels.
Time for a high-yield fact! If your patient has depressive symptoms prior to their cognitive decline, such as sad, depressed, or hopeless mood, lack of energy and motivation, and flat or tearful affect, think of pseudodementia.
This is very important as pseudodementia is reversible and should be treated as a depressive disorder. In this case, you’ll probably need to refer your patient for psychotherapy and prescribe an antidepressant, typically a selective serotonin reuptake inhibitor.
Alright, once you diagnose cognitive impairment, obtain brain imaging with a CT or MRI. Next, assess imaging findings and determine if there are any abnormalities other than brain atrophy.
If there are additional abnormalities, look for the presence of mass lesion. If you find it, diagnose a tumor as the likely cause of the cognitive impairment.

Brain tumor 2:57–3:25

Patients with tumors in the frontal or temporal lobes would be particularly at risk for cognitive impairment. Depending on the location of the tumor, they might also present with other signs and symptoms, like hemiparesis and seizures.
On the other hand, if there are imaging abnormalities but no mass lesion present, you should think of normal pressure hydrocephalus, vascular dementia, and HIV-associated neurocognitive disorder.

Normal pressure hydrocephalus 3:25–5:21

First, let’s focus on normal pressure hydrocephalus. In this case, the patient reports progressive difficulty with walking and urinary symptoms, such as urinary urgency and frequency, or in some cases, urinary incontinence.
On physical exam, you’ll notice significant gait abnormalities. In normal pressure hydrocephalus, the gait is slow, with small steps and a wide base.
Additionally, the patient has difficulty with turns, taking multiple steps to turn around. They might have gait apraxia, which is described as a magnetic gait because the feet look stuck to the ground as the patient shuffles around.
Lastly, perform a pull test to test postural stability. To do this, stand behind the patient and suddenly pull back on their shoulders.
Individuals who can maintain their balance will either not take any steps backwards or, at most, take one to two steps back.
However, individuals with normal pressure hydrocephalus have postural instability, meaning they will take multiple small steps backwards, and might even fall.
In that case, the pull test is positive. Finally, imaging reveals ventriculomegaly with minimal cortical atrophy and no evidence of CSF obstruction.
With these findings, consider normal pressure hydrocephalus and perform a lumbar puncture. If the lumbar puncture demonstrates a normal opening pressure, diagnose normal pressure hydrocephalus.
Here's a clinical pearl! Management of normal pressure hydrocephalus includes consideration of a permanent CSF shunt placement, such as a ventriculoperitoneal shunt, which can potentially improve cognition and gait.
Alright, now let’s take a look at vascular dementia. These patients have a medical history of cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and tobacco use.

Vascular dementia 5:21–6:13

Also, history will reveal multiple previous strokes. The patient or a loved one will describe that cognitive decline is occurring in a stepwise fashion that seems to correlate with the timing of prior strokes.
On the physical exam, you’ll typically notice focal neurologic deficits, such as visual field loss, weakness, or aphasia.
Also, you might note high blood pressure or an irregular heart rate. Finally, if the imaging shows multiple infarcts and extensive white matter microvascular disease, diagnose vascular dementia.
Next, let’s focus on HIV-associated neurocognitive disorder. Here, history reveals a known HIV infection.

HIV-associated neurocognitive disorder 6:13–7:12

The patient may or may not be compliant with highly active antiretroviral therapy. Their exam might demonstrate sensory loss in the distal limbs consistent with peripheral neuropathy.
You might also notice other signs of HIV-related conditions, such as oral candidiasis and lesions from Kaposi sarcoma. Finally, if brain imaging reveals confluent bilateral, symmetric, periventricular white matter disease, diagnose HIV-associated neurocognitive disorder, also known as HAND.
HAND can range from mild cognitive impairment to dementia. Despite normal or near-normal CD4 counts and compliance with antiretroviral therapy, many individuals will develop some degree of HAND.
Alright, let’s move on and discuss the causes of cognitive impairment with no abnormalities other than cerebral atrophy on brain imaging.

Dementia with Lewy bodies 7:12–8:43

In this case, you should first look for the presence of abnormal movements that are consistent with a movement disorder.
If present, think of dementia with Lewy bodies and Huntington disease. Individuals with dementia with Lewy bodies report slowness and stiffness of movement, as well as shaky hands at rest.
They also have fluctuations in level of alertness, visual hallucinations, and unpleasant, vivid dreams associated with kicking, punching, or screaming.
These unpleasant dreams are consistent with a REM sleep behavior disorder. On exam, the patient fluctuates in level of attention and alertness.
Additionally, the physical exam reveals rigidity and bradykinesia, which is a decrease in amplitude or speed with continued movement.
In most cases, you will notice a pill-rolling tremor, which is a hand tremor at rest with movements that look like the patient is rolling a pill between their thumb and index finger.
Finally, CT or MRI of the brain shows cortical atrophy. With these findings, diagnose dementia with Lewy bodies.
Now, here’s a clinical pearl to keep in mind! While dementia presents early on in dementia with Lewy bodies, patients with Parkinson disease develop cognitive impairment later in the disease course.
Switching gears and moving on to Huntington disease, which is associated with fidgety movements, usually of the face, arm, or leg; and trouble walking.

Huntington disease 8:43–10:11

History also reveals other family members with similar symptoms. In some cases, these patients might present with depression, aggressive behavior, and psychosis.
The physical exam reveals chorea, which are involuntary, irregular movements that can affect the face, limbs, or trunk; as well as athetosis.
Athetosis is similar to chorea but smaller in amplitude and more continuous, causing writhing movements of distal limbs.
When athetosis is present in the hand and fingers, it might look like the patient is playing the piano. Finally, you will notice motor impersistence, which is the inability to sustain a motor task, such as protruding the tongue or maintaining a hand grasp.
If brain imaging shows atrophy of the caudate and putamen, consider Huntington disease. Next, order genetic testing of the huntingtin gene.
If you identify a CAG trinucleotide repeat expansion in the huntingtin gene, diagnose Huntington disease. Remember that Huntington disease is an autosomal dominant disorder characterized by the phenomenon of anticipation, where following generations present with earlier and more severe symptoms.
Now, let’s look at individuals with cerebral atrophy on brain imaging with no signs of movement disorders. In this case, you should think of primary dementias, like Alzheimer disease and frontotemporal dementia.

Alzheimer disease 10:11–11:54

In Alzheimer disease, the patient or loved one reports slowly progressive changes in cognition over several years, particularly memory loss.
The patient tends to forget specific events, such as appointments, important dates such as birthdays, and where they just placed an item.
This is known as episodic memory loss. They also have visuospatial difficulties and trouble with executing tasks.
Finally, the patient might be a known carrier of the apolipoprotein E4 allele. On the exam, you might find frontal release signs, which are primitive reflexes that are normally present in a newborn but disappear after infancy.
However, these reflexes can reemerge in neurodegenerative conditions that affect the frontal lobe. For example, your patient could present with a positive palmomental reflex, in which stroking of the palmar muscles at the base of the thumb causes a contraction of the mentalis muscle of the chin.
Another important reflex is the grasp reflex, in which the patient will reflexively grasp an object gently placed in their palms, such as the examiner’s finger.
Also, you might notice rigidity and hyperreflexia. If imaging reveals hippocampal and temporal lobe atrophy, with or without diffuse cortical atrophy, highly suspect Alzheimer disease.
Lastly, let’s look at frontotemporal dementia, which is characterized by slowly progressive cognitive and behavioral changes over many years.

Frontotemporal dementia 11:54–12:56

The patient’s family usually reports disinhibition of behavior, such as being socially inappropriate and impulsive. Also, they might report that the patient is apathetic, has lost interest in usual hobbies and social events, and lacks concern for others.
On the exam, you might notice frontal release signs and aphasia. Finally, if the brain imaging reveals atrophy of the frontal and anterior temporal lobes, diagnose frontotemporal dementia as the likely cause of cognitive impairment.
Keep in mind that there are two variants of frontotemporal dementia. One is behavioral variant frontotemporal dementia, which has prominent progressive behavior and personality changes, while the other one is primary progressive aphasia, in which the patient has progressive loss of language.
Alright, as a quick recap... Once you diagnose cognitive impairment, order brain CT or MRI and assess if the brain atrophy is the only finding on imaging.

Review 12:56–13:38

If there are additional abnormalities, specifically a mass lesion, diagnose a brain tumor. On the other hand, if there are imaging abnormalities and no mass lesions, think of normal pressure hydrocephalus, vascular dementia, and HIV-associated neurocognitive disorder.
However, if brain atrophy is the only finding, you should consider movement disorders, such as dementia with Lewy bodies and Huntington disease; and primary dementias, like Alzheimer disease and frontotemporal dementia.