Dementia is one of the biggest global health crises of the 21st century, according to leading neurologists. More than 50 million people are living with the disease, and that number is expected to triple by 2050

Roughly 60-80 percent of dementia cases are Alzheimer’s disease. Specialists are raising awareness that neurodegeneration can begin years, and sometimes decades before a person becomes symptomatic. This is one reason early diagnosis is so crucial. 

In a recent PlatformQ Health CME program, Barrow Neurological Institute Professor Marwan Sabbagh, MD, FAAN and researcher at the Institute for Neurodegenerative Diseases, Florida Richard S. Isaacson, MD led a discussion about key steps for managing this challenging disease.

Alzheimer’s disease follows three phases:

  • Preclinical phase, where amyloid buildup may already be in progress
  • Mild cognitive impairment phase, where the patient has greater impairments than normal but can still care for themselves
  • Third phase, where more significant issues emerge, like memory loss and issues with everyday tasks such as driving or managing finances

Clinical signs of Alzheimer’s disease

Progressive neurodegeneration is characterized by loss of neurons, extracellular amyloid beta plaques, and intracellular neurofibrillary tangles (NFTs). These NFTs accumulate progressively in the neuron and are associated with its death. Abnormal accumulation of hyperphosphorylated-tau protein destabilizes neuronal microtubules and causes NFTs. Unlike amyloid beta plaques, formation of NFTs typically occurs in parallel to the progressive of cognitive decline. 

Risk factors for the disease include:

  • Advanced age
  • Certain medical conditions such as diabetes
  • Positive family history
  • History of head trauma
  • Loss of smell

Reducing the risk of Alzheimer’s disease

Although there is no magic fix to prevent Alzheimer’s disease, there are many modifiable risk factors, including:

  • Controlling blood pressure and cholesterol
  • Managing diabetes
  • Increasing exercise
  • Modifying sleep patterns
  • Continuing social engagement
  • Quitting smoking

Making an early diagnosis

“If a patient is 65 years old, the disease likely started in their brain at age 35-45,” explains Dr. Isaacson. “There’s a critical window of opportunity to try to work on primary or secondary prevention of cognitive decline, as well as delaying the progression of cognitive decline. We try to identify patients very early so we can figure out what’s treatable or reversible.”

Primary care practitioners (PCPs) can play an important role in early diagnosis by helping patients and their families talk about concerning symptoms. Patients often fear the stigma of Alzheimer’s disease, and may hide symptoms. Others may present with unusual behaviors or psychiatric symptoms. “It’s critical to build a relationship with a patient and take your own observations into consideration,” says Dr. Sabbagh. “If you have concerns, talk with their family member or other caregiver to ask if their mood or behavior has changed, and provide psychological support for the patient and family. Elder care case managers and attorneys can be helpful supports as well.”

Evaluating patients 

Evaluations include:

  • Detailed clinical history
  • Neuropsychological testing to determine which cognitive functions are impaired
  • CBC, basic metabolic panel, and liver function tests
  • Screening to exclude hypothyroidism
  • Screening to rule out neurosyphilis, if there is a family history
  • Brain scan if having any cognitive issues
  • Biomarker testing for Alzheimer’s disease
  • Serum B12 to exclude B12 deficiency
  • Genetic testing if there is a strong family history and/or early onset symptoms
  • Geriatric depression screen, if warranted 

“MRIs can be extremely valuable in the diagnostic process,” says Dr. Sabbagh. “If you look at the thin coronal cuts through the hippocampus memory center and there’s shrinkage, that’s pretty suggestive, when accompanied by symptoms.”

The neurologists noted that getting Alzheimer’s disease biomarker tests is also very important, and is the future of disease management. There is a disease-modifying agent that is now FDA approved, and more are in development. In clinical trials, biomarker blood tests are over 80 percent accurate in diagnosing the disease. 

Understanding Alzheimer’s disease treatment

There are three types of medications for Alzheimer’s disease:

  • Symptomatic medications. Oral medications such as Donepezil and Galantamine are prescribed for moderate-to-severe disease. These do not address the underlying disease or stop the rate of decline, but they can help with some symptoms. All of these have side effects such as weight loss and diarrhea, so it’s best to start at a low dose and titrate up to minimize these. Rivastigmine works similarly, but is available in a patch form. “None of these medications has shown efficacy in the mild cognitive stage but they are used off-label for that purpose,” says Dr. Sabbagh.
  • Behavioral targeting drugs. Although there are some drugs prescribed for behavioral symptoms of the disease, there are actually no on-label approved drugs for symptoms such as agitation, delusions, anxiety, and hallucinations.
  • Monoclonal therapies. “We’re starting to see these disease-modifying treatments emerge that are designed to provide meaningful slowing of decline,” says Dr. Sabbagh. “Amyloid is a huge driver of downstream pathology, and we should be targeting it early.” These medications include:
    • Aducanumab, which was the first such therapy, approved for mild cognitive impairment. It has been controversial, and has been used sparingly in the clinical setting. 
    • Lecanemab, the second approved therapy, which demonstrated the ability to slow cognitive decline in clinical trials. 
    • Gantenerumab, which is a shot that’s given to decreased amyloid beta.
    • Donanemab, which showed in clinical trials that it slowed cognitive decline by up to 30%. 

“These drugs work best in the earliest symptomatic phase,” says Dr. Sabbagh. He also cautions physicians to perform a baseline MRI to check for brain microhemorrhages prior to initiating any therapy. More than 10 microhemorrhages can placea patient at high risk of vasogenic edema and sulcal effusions (ARIA-E) and hemosiderin deposits (ARIA-H). If patients experience symptoms such as headaches or confusion, or imaging abnormalities emerge, it’s often advisable to stop dosing temporarily until the abnormalities resolve. 

A warning about antipsychotics

The greatest driver of morbidity as well as the top reason for long-term care placement of patients with Alzheimer’s disease is neuropsychiatric features such as agitation, anxiety, wandering, and aggression. There is no on-label drug for these behavioral symptoms. 

Antipsychotics are sometimes prescribed for paranoia or delusions, but they come with a black box warning. “They can increase mortality, and should be used with extreme caution,” says Dr. Sabbagh. “The biggest thing we can do instead of more medication is to teach caregivers to use redirection strategies. If we can redirect the patient without more medication, that is optimal.”

These medications have been studied thoroughly through the KDAD trial and only showed non-significant benefit. “We do not recommend prescribing these medications for patients with Alzheimer’s disease, yet it is still commonplace to do so. I would caution my fellow practitioners that there are risks of death and falls so be very careful when thinking of these.”

There is also strong data that music therapy offers many advantages for calming patients. Dr. Sabbagh recalled a patient who worked as an organist earlier in life. When he became agitated, the staff at his care center would sit him down at the organ and it helped relax him. 

A focus on prevention

When it comes to risk reduction, there is no one size fits all. People with diabetes are twice as likely to develop Alzheimer’s disease. Even moderate alcohol consumption increases risk. There are also differences in risks between men and women. For example, in women, the rapid loss of estrogen during perimenopause can accelerate amyloid buildup. 

There are steps people can take to lower their risk. One of the most important is blood pressure management. The Sprint Mind study demonstrated that controlling blood pressure can reduce the risk of cognitive impairment by 19%. 

Learn more about managing Alzheimer’s disease at our free CME program, now available on demand.