Alzheimer disease: Clinical sciences

Alzheimer disease, which is a neurodegenerative condition with slowly progressive cognitive and functional decline, is the most common cause of dementia in the developed world. Its pathology is characterized by extracellular deposits of amyloid plaques and abnormal intracellular accumulations of tau protein in neurofibrillary tangles.

There’s also a degeneration of cholinergic neurons in the nucleus basalis of Meynert, with a decrease in acetylcholine levels throughout the cortex. Now, the four main stages of this condition include mild cognitive impairment and mild, moderate, and severe Alzheimer disease.

Now, if your patient presents with a chief concern suggesting Alzheimer disease, several exams need to be done. First, obtain a focused history and physical exam. Be sure to perform a standardized screening cognitive exam, along with a depression screen, because many patients with Alzheimer disease or dementia have coexisting depression. Next, check vitamin B12 and TSH levels to rule out vitamin B12 deficiency and hypothyroidism, which are conditions that can cause cognitive impairment. Finally, order brain imaging with CT or MRI to ensure no structural processes are causing cognitive impairment.

History typically reveals slowly progressive cognitive decline, such as memory loss and difficulty with visuospatial tasks and executing tasks. In particular, these patients tend to forget specific events, like appointments, important dates such as birthdays, or where they just placed an item, which is known as episodic memory loss.

Also, they have difficulty with performing usual daily activities like self-care. Next, history will be negative for the use of medications or substances that can cause cognitive side effects, such as anticholinergics or excessive alcohol intake; and there will be no other medical conditions that could affect cognition, such as hepatic encephalopathy. Finally, your patient might be a known carrier of the apolipoprotein e4 allele, which is associated with an increased risk of Alzheimer disease.

Depending on the stage of the disease, your physical exam findings may vary. Early in the disease, the physical exam might be completely normal. Later, your patient might present with frontal release signs, which are primitive reflexes that are normally present in a newborn and disappear soon after infancy; however, these 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. You might also find rigidity and hyperreflexia.

Next, the screening cognitive exam, such as the Mini-Mental State Examination or the Montreal Cognitive Assessment, will be abnormal; while the depression screen may or may not be positive. Labs will reveal normal vitamin B12 and TSH levels. Finally, brain imaging might show atrophy of the bilateral hippocampi, temporal lobes, or the cortex diffusely. With these findings, suspect Alzheimer disease.

Your next step is to obtain an amyloid PET scan, which detects amyloid deposition in the brain parenchyma. Alternatively, you can order CSF or plasma biomarker assays. These biomarkers include plasma phosphorylated-tau 217, or the ratio of amyloid-beta 42 peptides to amyloid-beta 40 peptides in the CSF.

If the amyloid PET is positive for amyloid deposition or if the biomarker assays are abnormal, diagnose Alzheimer disease. Keep in mind that these diagnostic methods are not yet readily accessible for many patients, so their use is limited in clinical practice, and the diagnosis of Alzheimer disease currently primarily relies on clinical manifestations.

Once you diagnose Alzheimer disease, use the cognitive testing results to assess the clinical stage of the disease. If your patient is still able to perform daily activities independently despite some difficulties, such as with less efficiency, the patient has mild cognitive impairment. At this stage, the patient does not yet have dementia, which is the loss of ability to function independently due to cognitive impairment.