Gary W. Small, MD

Age is the greatest risk factor for memory loss and dementia, defined as a cognitive decline that interferes with independent functioning. By age 45, the objective memory performance of average individuals is lower than it was during their twenties, but for most, these mental slips are minimal and do not progress.

For those with a family history of Alzheimer disease (AD), these agerelated memory complaints cause considerable anxiety: patients worry that their normal aging symptoms are the initial indication of a progressive cognitive impairment that they have observed in their relatives.

AD is the most common cause of dementia. It has a gradual onset and progression and leads to abnormal protein deposits-amyloid plaques and tau tangles-that accumulate in the brain regions that control thinking and memory. However, many other conditions can cause dementia, such as depression, adverse effects of medications, thyroid imbalances, and other medical illnesses. Treating these underlying medical conditions may cure a reversible dementia or lead to partial symptom improvement.

Other irreversible neurodegenerative diseases that cause dementia include Lewy body disease, vascular dementia, and frontotemporal degeneration. Even if there is no cure for the underlying cause of a dementia, treatments are available that stabilize symptoms and help people remain healthier longer.

A clinical assessment of cognitive issues includes a search for risk factors, such as smoking history, lack of sleep, prior head trauma, or history of untreated high blood pressure or high cholesterol. A detailed inventory of the patient’s medications is essential. Many prescription and over-thecounter drugs for allergies (diphenhydramine) or sleep (eg, Sominex, which also contains diphenhydramine) can impair cognition. Sedating medicines, narcotic agents, histamine H2-receptor antagonists (eg, famotidine, cimetidine) for gastrointestinal problems, cardiac medications such as digoxin and beta-blockers, corticosteroids, NSAIDs (eg, naproxen, ibuprofen), and antibiotics are all among the list of medicines that may contribute to symptoms.

A mental status assessment will help determine the patient’s degree of cognitive impairment, as well as the presence of depression or anxiety that can worsen memory. A brief evaluation of cognitive abilities will determine degree of cognitive impairment, and neuropsychological cognitive testing may be ordered to detail these deficits through neuropsychological testing.

A physical and neurological examination and screening blood tests for thyroid, metabolic, and other possible abnormalities are recommended to uncover medical causes of confusion. To ensure that a tumor, stroke, or other brain abnormality is not present, a computed tomography (CT) or magnetic resonance imaging (MRI) scan is performed.

For patients with a diagnosis of Alzheimer dementia, symptomatic medications temporarily stabilize symptoms but do not cure the disease. These medicines help patients remain at a higher functional level longer than if they did not take the medicine and may benefit patients with other forms of dementia such as Lewy body disease and vascular dementia.

Patients are often started on a cholinergic medicine, such as donepezil or a rivastigmine patch (if patients have adverse effects from the former). Cholinergic medicines are thought to exert their effects by increasing availability of acetylcholine, which is important for normal cognitive functioning.

Once the patient is stabilized on one of these cholinergic drugs, the clinician often adds a second symptomatic medication, the 

-methyl-D- aspartate (NMDA) receptor antagonist memantine. We know that combining a cholinergic drug with memantine leads to a better outcome than using either type of medication alone. In addition to helping with cognitive symptoms of dementia, these symptomatic medicines have been shown to delay the emergence of agitation and other behavioral symptoms associated with dementia.

It is important for clinicians to manage patient and family expectations about medication benefits. One strategy is to explain that if the patient tolerates the drug, then that patient will do significantly better than without the medication after a year, but some patients do experience temporary improvement. However, if there is an expectation of definite improvement and it does not emerge, patients and family members may become discouraged and prematurely discontinue the medicine.

It is also helpful to inform patients and families that symptoms eventually progress. However, remaining on the medicine when that occurs will lead to a slower rate of cognitive decline than discontinuing the medication.

Recent research has shown that a healthy lifestyle can protect brain health as people age. A healthy brain lifestyle includes regular physical activity, balanced nutrition, stress management, and mental stimulation.

Healthy lifestyle programs that seem most effective include three elements: educating patients about the association between daily habits and brain health; setting reasonable goals that are not too daunting; and providing feedback of initial success to motivate participants.

Many families express interest in volunteering for research protocols involving new dementia interventions. Usually patients can remain on their symptomatic treatments while participating in research.

A variety of interventions are currently being tested, including new medications, vaccines, supplements, antibody blood infusions, nasal insulin spray (diabetes increases dementia risk), and focused ultrasound waves targeting the brain’s hippocampal memory center in attempts to activate these neural circuits. Most of the clinical trials are testing disease-modifying treatments, which would lead to an enduring change in the clinical progression of AD by interfering with the underlying pathophysiological mechanisms of the disease.

Dr Small is Parlow-Solomon Professor on Aging, Professor of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA; Director of the UCLA Longevity Center; and Director, Geriatric Psychiatry Division at Semel Institute for Neuroscience and Human Behavior, Los Angeles. 

Dr Small spoke at the 2019 Psych Congress in San Diego, CA, in a presentation titled “Age-related cognitive decline: clinical applications of new research.”

This article was originally published on 10/7/19 and has since been updated.

The author reports that he is Consultant/Advisor: Acadia, Actavis/Allergan, Avanir, Forum, Genentech, GlaxoSmithKline, Herbalife, Handok, Otsuka, RB Health, Roche, Theravalues Speakers Bureau: Acadia, Actavis/Allergan, Avanir, Forum, Herbalife, Handok, Otsuka, RB Health, Theravalues, Board Member: CereMark; and Stockholder: CereMark.

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Patients with a family history of Alzheimer disease worry that normal aging symptoms are the initial indication of a progressive cognitive impairment that they have observed in their relatives. A variety of interventions are discussed.

Gary W. Small, MD

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