Description

Dementia is a medical term used to describe a syndrome of memory impairment that is severe enough to affect an individual’s daily functioning including social and occupational interactions. The cognitive impairments caused by dementia are not a normal part of aging. 

Many types of dementia have been identified including Alzheimer's disease (AD), vascular dementia (VasD), Lewy body dementia (LBD), Frontotemporal dementia (FTD) and Parkinson’s disease related dementia (PDD).  People can also develop mixed dementia which is a combination of more than one type of dementia.

AD was first described in 1907 by a German neuro-psychiatrist, Alois Alzheimer. People with this disease generally experience progressive memory loss, disorientation and language problems.

VasD occurs when a person experiences strokes that affect key portions of the memory pathway or has multiple strokes that affect their ability to process information. The characteristics of VasD vary depending on the location of the vascular events.

LBD was named after Dr. Frederich H. Lewy, the neurologist who discovered Lewy bodies while working in Dr. Alois Alzheimer's laboratory during the early 1900s. Alpha-synuclein, the chief component of Lewy bodies, is found widely in the brain, but its function is not known.  People with LBD may present with symptoms of sleep disturbances, well-formed visual hallucinations, slowness, gait imbalance, and other parkinsonian movement features such as rigidity (muscle stiffness). These features, as well as early visuospatial impairment, may occur in the absence of significant memory impairment.

FTD was first described in 1892 by Arnold Pick, but interest in this disease lagged until the 1990's. FTD generally presents with changes in behavior, language problems and/or difficulties with decision making. In contrast to AD, People with FTD do not have pronounced problems with memory until later in the disease.

PDD develops in people with Parkinson’s disease which presents with movement symptoms that include tremors and shakiness, muscle stiffness, a shuffling step, stooped posture, difficulty initiating movement and lack of facial expression. As brain changes caused by Parkinson’s gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task.

Alzheimer’s dementia is the most common type of dementia with an estimated 5.8 million Americans suspected to have the disease in 2019. Age is the main risk factor for Alzheimer's disease. Ten percent of people over the age of 65 have AD, while almost 32% of those over age 85 and older suffer from AD.  VasD accounts for 15 to 20% of dementias and can present at any time during an individual’s lifetime, but generally occurs later in life. LBD accounts for 10 to 25% of cases of dementia. FTD accounts for 5-7% of diagnosed dementias.  People with FTD tend to present in their 50's, which is earlier than people with AD.

As indicated, there are a number of dementing illnesses. The causes for several are not known.  Current research suggests that some forms of dementia are the result of build-up of protein in the brain that affects normal brain functions.  In some cases, dementia is caused by reversible causes, such as B12 deficiency and thyroid dysfunction, and prompt evaluation and treatment are crucial.

The genetic bases of some dementias are not completely clear due to variable penetrance and inheritance patterns.  It should be noted that predominantly genetic/heritable forms of dementia tend to present in earlier in life (before the age of 65) and are extremely rare. In AD, the most commonly associated genes are Presenilin-1, Amyloid precursor protein gene (APP) and Presenilin 2 gene. Most familial frontotemporal dementia is caused by mutations in three genes - C9ORF72, and genes for the proteins tau (MAPT) and progranulin (GRN). There are rare forms of genetic vascular dementia which usually involves mutation in the NOTCH3 gene causing cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).  Lewy Body dementia has a strong inheritance pattern but no mutations have been identified so far. The APOE e4 variant is thought to be the strongest genetic risk factor for DLB, as it is for Alzheimer's disease. Variants in two other genes, glucocerebrosidase (GBA) and alpha-synuclein (SNCA), also affect the risk of a person developing DLB. Alpha-synuclein is the main protein within Lewy bodies, which are found in both DLB and Parkinson's disease. 

The course of AD, FTD and Lewy body dementia vary considerably, but they are always progressive. VasD tends to be a more static disease unless an individual has recurrent strokes.

Symptoms

Early symptoms of Alzheimer's disease include short term memory loss and disorientation, which may be associated with difficulty navigating to familiar destinations. As the disease progresses, these symptoms increase and word finding problems (aphasia) may emerge. Many people also lose insight into their condition and are unable to understand that they have cognitive problems. Depression, agitation and paranoia may also be present. Eventually, people with may forget how to perform simple tasks of everyday life (activities of daily living including getting dressed, bathing, toileting, standing/walking, and eating). They may also lose the ability to recognize faces and objects. Twenty to thirty percent develop symptoms such as slow movement and trembling.  Seizures can occur in 10-20 percent of people with Alzheimier’s, often late in the disease.

The presentation of FTD varies depending on the part of the brain first affected. Marked changes in mood, behavior or personality are common symptoms, but some people first present with severe language problems (aphasia) or difficulties making decisions (executive dysfunction). Memory is generally not affected early in this disease. As FTD progresses, individuals may develop impairments similar to AD including memory loss and disorientation.

VasD may present with any of the symptoms seen in AD or FTD.

Lewy body dementia is associated with impairments in thinking and reasoning, fluctuating levels of alertness, and also disorientation from one time of day to another or from one day to the next. Symptoms typical of Parkinson disease are also evident including shuffling gait, imbalance and slowness in movement.  People may develop well-formed visual hallucinations and delusions as well as impairments in visual processing.  People with Lewy Body dementia may also develop REM (rapid eye movement) behavior disorder which is associated with, often violent, dream reenactment and kicking/punching while asleep.  Memory loss is usually less prominent than in AD.

Parkinson’s disease related dementia may present with impaired short-term memory, concentration and judgment with additional impairments in visual processing, visual hallucinations, and delusions. People may also develop anxiety, irritability and sleep disturbance such as REM sleep disorder.  An estimated 50 to 80 percent of People with Parkinson’s disease eventually develop dementia as their disease progresses, on average within 10 years of their initial diagnosis. 

Diagnosis

There is no single test to diagnose Alzheimer's disease, frontotemporal dementia or vascular dementia.  Researchers are identifying biomarkers that may lead to the development of blood tests which can be used to establish a diagnosis. Often brain imaging, such as CT scan or MRI, is performed to evaluate for structural changes associated with dementia such as hydrocephalus, vascular disease, and hippocampal atrophy (decrease in size) of the part of the temporal lobes integral to memory formation).  Blood tests are done to rule out reversible causes of dementia such as vitamin deficiencies (thiamine, B12 and folate), metabolic dysfunction (thyroid disease) and infections (Lyme disease, HIV or syphilis). Certain medications such as benzodiazepines, opioid pain medications, and sleep medications can increase risk for development of dementia.

To obtain a complete and accurate diagnosis, it is important to have a complete physical exam, health history, and neurological consultation. Additional tests such as electroencephalography (EEG) can help to rule out seizure as cause of memory loss.  Neuropsychological testing is also important in characterizing patterns of cognitive impairment and can objectively help monitor cognitive functioning over time.  Positron emission tomography (PET) scan and Amyloid scan can also be used to help establish diagnoses in complicated cases.

Treatment

There is currently no cure for any of the dementias. Treatments are currently available help to stabilize cognitive symptoms and reduce the rate of decline, but they cannot restore memory function which has been lost.

The most common class of medications used to treat dementias inhibits the breakdown of a chemical in the brain known as acetylcholine which is integral to communication between brain cells.  This class of medications, known as acetylcholinesterase inhibitors, includes:

• Donepezil (Aricept)
• Galantamine (Razadyne)
• Rivastigmine (Exelon)

Common side effects associated with the above medications include gastrointestinal upset, loss of appetite, increased urinary frequency, muscle cramps, and vivid dreams.

Another medication, memantine (Namenda) was approved for use in moderate to severe dementia in 2003 and is commonly used in combination with one of the acetylcholinesterase inhibitors listed above.  It is an NMDA (N-methyl-D-aspartate) receptor antagonist impacting another receptor pathway.  Potential side effects of memantine include constipation, dizziness, headaches, and sleepiness. 

In addition to medications for neuroprotection, people with dementia also benefit from moderate physical activity, social and cognitive stimulation, and diet (specifically, adherence to the Mediterranean diet, characterized by high intake of whole grains, legumes, vegetables, and fruits, only moderate consumption of alcohol, and a high monounsaturated-to-saturated fat ratio).

Research aimed at discovering new methods of treating these diseases is ongoing.

Useful links:

American Alzheimer’s Association