WHAT IS A NEURODEGENERATIVE DISEASE (NDD)?
A Neurodegenerative Disease is a condition that affects neurons in the brain, causing symptoms such as memory loss, moodiness, anxiety, depression, and agitation. Treatment for each neurodegenerative disease varies, and incorrect treatment may not be helpful or could be detrimental. Consulting experts in the field with specialized training is necessary to ensure the correct diagnosis.
NDD Terminology
Dementia – Typically refers to a broad category of neurodegenerative diseases. However, not all causes of dementia are degenerative. For example, a single stroke may result in cognitive difficulties, but the symptoms remain largely stable over time and do not progress. Most commonly, the term is used in context with progressive neurodegenerative disease.
Memory disorder – Several conditions that can affect memory. These disorders may also affect language, decision making, attention, and visual perception. Alheimer’s disease is most familiar NDD, or “memory disorder.”
Mild cognitive impairment (MCI) – Cognitive change but with no decline in daily function. The individual and others around them may notice subtle change. MCI is a broad category of cognitive difficulty in one or more areas (language, concentration, judgment & planning, memory, and visual perception). MCI is not necessarily progressive, but it can be the first stage in a neurodegenerative disorder even when only mild symptoms are present.
MCI indicates an increased risk of a future diagnosis of dementia. Severe depression, medications, poor sleep, pain, and other concomitant medical issues can be risk factors for MCI.
Normal age-related cognitive changes – The mind and brain change as we age.
Typical cognitive changes include:
- Slower thought process
- Taking longer to learn something new
- Decreased ability to multitask
- Occasional temporary difficulty remembering a word or name
- Occasional misplacing an item such as glasses or keys
- Occasionally walking into a room and forgetting why
Warning signs that cognitive changes may be more serious than those caused by normal aging: Frank difficulty retrieving information from memory. An individual may forget that a conversation occurred and have difficulty managing finances. These types of cognitive changes indicate that an individual should consult with an expert for a comprehensive evaluation.
Prodormal Neurodegenerative disease – A disease state at a microscopic and cellular level that is not yet observable with MRI scans or neuropsychological testing. The term has become increasingly important as the disease processes of many neurodegenerative diseases become better understood. Understanding the prodromal state is increasingly useful in understanding disease intervention.
Outdated terms: Senile dementia, senility, and demented are outdated, have negative connotations, and are no longer used.
What Causes NDDs?
Most NDDs begin years or decades before symptoms are present. Research shows that, in every neurodegenerative disease, there is an abnormal protein involved which becomes toxic to the nerve cells, resulting in cell death and cognitive decline. As the disease progresses, additional nerve cells can become overstimulated and die as well. Furthermore, with cell death, inflammation ensues, causing further cell death. Ultimately many factors contribute to disease progression in its later stages.
Proteins involved in neurodegenerative diseases:
Beta-amyloid – A major protein involved in Alzheimer’s disease, but can also be present in Dementia with Lewy Bodies
Tau – Along with beta-amyloid it comprises Alzheimer’s disease pathology. However, it is can also be present in other NDDs such as Progressive supranuclear palsy, Croticobasal syndrome, types of Frontotemporal Lobar Degeneration and Chronic Traumatic Encephalopathy
Synuclein – A protein commonly seen in Parkinson’s disease (with or without cognitive changes), Dementia with Lewy Bodies and Multiple System Atrophy
TDP-43 – Present in Amyotrophic Lateral Sclerosis (ALS), types of Frontotemporal Lobar Degeneration, Hippocampal Sclerosis (progressive scarring of hippocampus)
Huntington – A mutated protein present in Huntington’s disease
PrPSc – Primary protein in Creutzfeldt-Jakob disease (CJD)
Risk Factors for NDD
Several conditions increase the risk for developing future NDDs, including:
- Cardiovascular disease
- Cerebrovascular disease
- Smoking
- Prior head injury (ranging from concussion to severe brain damage)
- Age
- Genetics
- Diet
- Sleep deprivation
- Alcohol use
- Depression
- Poor fitness
- High blood pressure
- Uncontrolled diabetes
Diagnosis
An experience and subspecialized physician obtains a thorough and detailed timeline of symptoms and their progression. Cognitive testing is used to evaluate for cognitive changes. Occasionally, more involved testing is required in the form of formal neuropsychological testing, which evaluates each cognitive area in detail. MRI is part of a routine evaluation for diseases of the central nervous system and will allow the physician to evaluate for strokes, bleeding, tumors and brain shrinkage.
Treatments
At present there are no drugs that can alter the underlying disease state. Just as Tylenol will only alleviate the symptoms of arthritis for a period of time, the available medications can simply delay symptom progression for a period. However, many lifestyle factors can be enhanced to stave off symptoms and increase quality of life.
While a cure to most NDDs remains elusive, strategies can be taken to slow down symptom progression and provide higher quality of life. In addition, for patients with MCI, Transcranial Magnetic Stimulation (TMS) may turn back time on symptoms by up to two years.
Kaizen Brain Center Treats the Following Neurodegenerative Diseases
Late-Onset Alzheimer’s disease (AD) – The most common neurodegenerative disease (approximately 60-70% of all neurodegenerative diseases). Late onset refers to symptom onset after 65 years of age. AD is the prototypical memory disease, most commonly presenting with short term memory loss. Caused by abnormal accumulation of beta-amyloid and tau proteins in the brain.
Common symptoms include:
- Forgetting recent conversations
- Repetitive questioning
- Getting lost in familiar places, particularly while driving
- Difficulty with planning and organization
- New difficulty managing bills or finances
- New difficulty with electronic equipment
Young-Onset Alzheimer’s disease/Early-Onset Alzheimer’s disease (AD) – A rare type of dementia in individuals 65 and younger. It is frequently misdiagnosed. Unlike late-onset Alzheimer’s disease, young-onset AD can present with a broad variety of symptoms, which may include delusional thoughts (paranoia, false beliefs), difficulty with decision making and using judgment, and language difficulty.
Frontotemporal lobar degeneration – A behavioral-variant of Frontotemporal Degeneration (FTD). It is the most common type of dementia in 40-50 year-old individuals. Common symptoms include changes in food preferences toward sweets and overeating, impaired judgment, lack of empathy, apathy, repetitive complex rituals, and loss of socially appropriate behavior. Most commonly caused by TDP-43 and tau.
Primary Progressive Aphasia – A primary disorder of language. Difficulties extend to reading, writing, speech, and any other form of communication. Common symptoms include prominent and frequent difficulty finding the correct words, pauses in speech, and difficulty naming objects. Speech is strained and slow with abnormal grammar. The individual has difficulty understanding conversations and directions, and difficulty understanding the meanings of words. Age of onset varies greatly. Caused by tau and beta-amyloid, tau only, or TDP-43.
Posterior Cortical Atrophy – Also known as a ‘visual variant” of AD, as it is caused by the same abnormal proteins. It is a disorder of visual perception and processing. It often begins with subtle symptoms of difficulty reading, navigating, recognizing objects and faces, and bumping into objects. The individual has difficulty perceiving or reaching an object directly in front of them. The underlying cause is most often Tau and Beta-amyloid.
Parkinson’s disease and Parkinson’s disease dementia – Parkinson’s disease is classified as a primary movement disorder with progressive difficulty with movement and walking. Classic symptoms consist of a coarse and relatively slow tremor in one or both hands and/or legs that is most pronounced when the limb is at rest. As the disease progresses, a characteristic shuffling gait develops, and the natural swinging of arms while walking diminishes. There is also notable stiffness called ‘rigidity’ that develops in the arms and legs. Facial expressions are often decreased, a feature described as a “masked” face. A stooped posture is also common.
Cognitive changes can also occur in Parkinson’s disease; however typically motor symptoms predate cognitive changes by 10-20 years. REM sleep behavior disorder is also common. Loss of REM sleep paralysis, called “REM sleep behavior disorder (RBD),” often accompanies DLB where individuals act out their dreams, sometimes in a violent manner resulting in injuries to their bed partner. Common cognitive changes include slowness of thought, difficulty concentrating, memory difficulties, delusions, hallucinations, and impaired judgment. Similar to Dementia with Lewy Bodies, Parkinson’s disease is caused by the accumulation and propagation of synuclein forming Lewy Bodies seen in microscopy.
Dementia with Lewy Bodies (DLB) – Falls under the umbrella term “Parkinson’s plus syndromes” because some symptoms of Parkinson’s disease are required for the diagnosis. Although controversy exists as to whether DLB is a variant of Parkinson’s disease (PD) or its own entity, there are distinguishing features of DLB that set it apart from classic PD. DLB shows symptoms of cognitive decline either before or concurrently with Parkinson’s-like symptoms. Recurring visual hallucinations can be seen early in the disease which are very vivid and commonly consist of people or small animals.
Significant fluctuation in alertness and confusion can be seen throughout the day with extremes ranging from staring spells, poor responsiveness, extreme confusion, and near normal clarity. Difficulty with visual processing may also be present with individuals experiencing early difficulty finding their way in new locations. Memory can be relatively preserved in contrast to Alzheimer’s disease. Loss of REM sleep paralysis, called “REM sleep behavior disorder (RBD),” often accompanies DLB where individuals act out their dreams, sometimes in a violent manner resulting in injuries to their bed partner. DLB is caused by propagation of synuclein which form the characteristic Lewy Bodies seen in microscopy.
Progressive Supranuclear Palsy (PSP) – Categorized as a Parkinson’s plus syndrome as it shares features of Parkinson’s disease while being its own distinguishable entity. Characteristic symptoms include falls early in the course of the disease, difficulty walking, and shuffling; however, unlike with Parkinson’s disease, the posture in this disorder is often over extended rather than stooped. As the disease progresses, voluntary eye movements, especially looking downward, may become difficult.
Cognitive symptoms typically accompany PSP, and there are many subtypes of the disease. Common cognitive changes include changes in behavior and frontal lobe dysfunction presenting with impaired judgement, slow thought process, and difficulty shifting between tasks. Responses to question can be slowed, and slurred speech is very common. PSP is caused by accumulation and propagation of Tau, but with little or no beta-amyloid deposition.
Multiple system atrophy (MSA) – A rapidly progressive Parkinson’s plus disease with prominent symptoms of autonomic nervous system dysfunction such as slow or fast heart rate, position-dependent drop in blood pressure, urinary difficulties, erectile dysfunction, and breathing difficulties while sleeping, with a high pitched wheezing sound during inspiration. As in Parkinson’s disease and Dementia with Lewy bodies, individuals may experience loss of REM sleep paralysis and act out their dreams, sometimes violently. MSA is sometimes divided into two subtypes: MSA-C and MSA-P. MSA-C shows prominent difficulty with coordination and a wide-based ‘drunken’ walk. MSA-P has more classic Parkinson’s disease symptoms, though they are more symmetric, and tremor is often absent. Cognitive impairment is not a prominent presenting feature but may occur later in the disease process. It is caused by the accumulation and propagation of synuclein, but unlike in Parkinson’s disease and Dementia with Lewy bodies, the synuclein does not form Lewy bodies.
Vascular cognitive impairment – Large strokes or numerous small strokes over time can cause cognitive decline and ultimately dementia. While vascular cognitive impairment is not progressive in the same sense as a neurodegenerative disease, vascular damage is irreversible. Unlike neurodegenerative disease, progression of vascular disease can be slowed down by treating vascular risk factors such as diabetes, high cholesterol, and high blood pressure.
Corticobasal syndrome – Corticobasal syndrome, formerly called corticobasal degeneration is a heterogeneous condition that can be caused by multiple different pathologies, including TDP-43, synuclein, beta-amyloid and tau. The syndrome typically presents with loss of dexterity and clumsiness in the hands. Similar to Parkinson’s disease, stiffness is often present, but tremors are less common. In addition, sudden jerks of the limbs may be seen. A unique symptom called “alien limb phenomenon”may be present, in which the individual will feel that one of their limbs has a will of its own and seemingly moves on its own. Cognitive impairment is a prominent part of the CBS and commonly includes language impairment and behavioral changes, though various other impairments may be seen as well. CBS may represent an overlap syndrome with multiple underlying pathologies presenting a heterogeneous clinical entity.
Creutzfeldt-Jakob disease – Creutzfeldt-Jakob disease is a rapidly progressive neurodegenerative disease with life-expectancy less than 1 year and often only a few months. The disease is most commonly referred to as “mad cow disease,” and while that disease is a subtype of CJD, only an exceedingly small fraction of the disease is caused by contaminated meat. The cause of Creutzfeldt-Jakob disease is the protein PrPSc, which causes exponentially more and more misfolding of the normal protein present in the brain. Common symptoms are clumsiness, abnormal movement of the arms and legs, loss of balance, and slurred speech.
Subspecialty Training
The subtleties of neurodegenerative disease are easy to miss, and indeed many are misdiagnosed before an individual seeks a specialized expert opinion. More often that not, symptoms are thought to be psychiatric when the individual is young or the disease is rare. Subspecialty training is of paramount importance for an accurate diagnosis and the correct treatment. Understanding the progression of the disease help improve quality of life and avoid complications of disease related comorbidities.
Early Prevention and Treatment
Evidence shows that the molecular process of Alzheimer’s disease and other dementias starts at least 15-20 years before the onset of memory complaints. Kaizen providers use evidence-based strategies to help prevent, diagnose, or treat Alzheimer’s disease at very early stages to help change the illness trajectory.