Conditions We Treat
Alzheimer’s disease, sometimes abbreviated as AD, is the most common cause of dementia in older people living in North America and Europe. It was discovered in the early 20th century by Dr. Alois Alzheimer, and people found to have this condition often – not always – show forgetfulness of recent events and conversations early in the course of their disease. The forgetfulness generally gets worse over time, and new symptoms impacting orientation, language, or decision making can appear.
Alzheimer’s disease vs Dementia
The usage of “Alzheimer’s disease” can be confusing. Sometimes, it is used to describe the abnormalities doctors and scientists see in the brain of someone who has passed away. It can also be used to describe dementia in general, especially in the media or other non-medical settings. While Alzheimer’s disease is the most common cause of dementia in Western societies, there are other causes of dementia not related to Alzheimer’s disease. It is therefore most appropriate to use these terms in the following way:
- Dementia – a clinical condition in which new cognitive difficulties – memory loss, struggling to find the word, poor decision making – are interfering with their ability to work, live, and function independently.
- Alzheimer’s disease dementia or Alzheimer’s dementia – dementia caused specifically by Alzheimer’s disease and not something else.
Dementia vs. Mild Cognitive Impairment
Unlike strokes or heart attacks, people do not develop Alzheimer’s dementia overnight. Older adults often have brain changes of Alzheimer’s disease for years before the first symptoms appear, and these first symptoms are very mild. While mild changes in thinking and memory can be a part of normal aging, they can also herald the earliest stage of dementia. Some people with these more subtle memory symptoms (which are generally not interfering with function) are diagnosed with “mild cognitive impairment” or MCI. A few studies suggested that up to 80% of people diagnosed with MCI will go on to develop Alzheimer’s dementia within 5 years, but most studies have found that about 40-60% of people with MCI progress to develop Alzheimer’s dementia.
Biological diagnosis of Alzheimer’s dementia and MCI due to Alzheimer’s disease
For a long time, doctors could only confirm the diagnosis of Alzheimer’s dementia when neuropathologists examined people’s brains under the microscope after they had passed away. Key features of Alzheimer’s disease include plaques and tangles, and it was found that about 25-35% of people diagnosed with Alzheimer’s dementia while they were still living ended up not having plaques and tangles in their brains. Because we cannot easily biopsy the brain, doctors and scientists had to come up with creative solutions to confirm the presence of plaques and tangles even when forgetfulness is mild.
After a lot of research including work done by Rutgers faculty, we are now able to measure levels of key proteins which make up plaques and tangles in people’s spinal fluid to diagnose Alzheimer’s disease, and visualize plaques in the brain on PET scan to exclude Alzheimer’s disease. People with MCI and abnormal spinal fluid markers are considered to have MCI due to Alzheimer’s disease, and they are most likely to progress to Alzheimer’s dementia within 5 years following diagnosis. These diagnostic approaches are especially important with new drugs targeting plaques and tangles on the horizon.
Frontotemporal dementia (FTD) or behavioral variant FTD is the second most common cause of dementia for those under the age of 65. People often develop prominent personality and behavioral changes from their baseline that get worse over time. These changes can sometimes be misdiagnosed as depression, late-life bipolar disorder, late-life schizophrenia, or even mid-life crisis. Memory is often preserved early in the disease. People with FTD can also demonstrate significant restlessness which makes sitting through a medical appointment challenging; constant pacing or picking behaviors; excessive eating or new addictions (alcohol drinking, smoking).
A set of conditions related to FTD are collectively called Primary Progressive Aphasia (PPA). A key feature shared by the different PPA forms is impaired language function. People with PPA can have difficulties with finding the right words, speak the words they know how to say, or understanding what others are saying. With further testing, doctors are often able to provide a more detailed diagnosis such as a semantic, non-fluent/agrammatic, or logopenic variant of PPA.
Causes of FTD/PPA
About 15-20% of people with FTD or PPA diagnosis actually have Alzheimer’s disease changes in their brains, and these can be reliably diagnosed by a spinal fluid test. In the majority of the cases, FTD and PPA are caused by one of two changes in the brain: TDP-43 or Tau. TDP-43 is also a key feature in AMYOTROPHIC LATERAL SCLEROSIS (ALS, also known as Lou Gehrig’s disease), and people with FTD/PPA due to TDP-43 may develop ALS. Tau is a key feature in movement disorders such as PROGRESSIVE SUPRANUCLEAR PALSY (PSP) and CORTICOBASAL DEGENERATION (CBD). The same spinal fluid test to identify atypical cases of Alzheimer’s disease can distinguish between TDP-43 and Tau causes of FTD/PPA.
Genetic forms of FTD/PPA
FTD and PPA have a greater heritable component than Alzheimer’s disease, and a number of genetic mutations have been identified to cause familial FTD/PPA. Mutations are changes in the DNA which can be passed from a parent to a child, and each child of a parent with familial FTD/PPA has a 50% chance of inheriting the gene responsible for the disease. While there are no treatments which can arrest brain changes linked to TDP-43 or Tau, there are on-going research studies to design treatment trials for genetic forms of these diseases.
Dementia with Lewy bodies (DLB), also known as Lewy body dementia or Lewy body disease, is a common cause of dementia in older people. People with DLB usually have symptoms which resemble both Alzheimer’s disease and Parkinson’s disease. These include forgetfulness, troubles with directions, balance issues with increased frequency of falls, slowed walking, and tremors. If someone experiences hallucination (seeing or hearing something that is not there) early in the course of memory decline, DLB is often the cause. Other associated symptoms can include acting out dreams while asleep, passing out when standing up, and worsening constipation.
DLB has been linked to abnormal clumps of alpha-synuclein (alpha-syn or α-syn) in the brain. DLB can be difficult to diagnose because not everyone is known to have the same symptoms. For example, acting out dreams at night may only be noticed if someone undergoes a sleep study, and some people report seeing dead relatives while others report seeing just shadows out of the corner of their eye. Similarly, a detailed neurological examination is necessary to identify mild changes in balance.
People with DLB usually respond very favorably to a class of drugs used to treat Alzheimer’s disease. At the same time, people with DLB are extremely sensitive to some medications commonly prescribed by primary care doctors. If you have been diagnosed with DLB, it is important to make sure you are not exposed to these medications.