Alzheimer's Disease

OVERVIEW AND PATHOLOGY

Alzheimer’s disease is a progressive disorder of memory, language, visuospatial functioning, and executive control.  Microscopic inspection of the brain at autopsy shows the accumulation of several misfolded proteins that accumulate in the brain.  Alzheimer’s disease requires the accumulation of these proteins, including amyloid and tau. Amyloid accumulates in the form of neuritic plaques outside of the brain cells or neurons.  Amyloid appears to be age-dependent, and its accumulation occurs in all of us as we age. 

A second protein is called tau, and this accumulates in the form of neurofibrillary tangles that can be seen inside neurons. The cognitive difficulties experienced by individuals with Alzheimer’s disease reflect in large part the anatomic distribution of tau in the brain.  Thus, as tau accumulates in the hippocampus, individuals with Alzheimer’s disease experience increasing memory difficulty; as tau accumulates in the temporal lobe, individuals with Alzheimer’s disease experience increasing difficulty with word-finding, reading and comprehension; as tau accumulates in the parietal lobe, individuals with Alzheimer’s disease experience increasing difficulty with visuospatial relationships and getting lost in topographic space; and as tau accumulates in the frontal lobe, individuals with Alzheimer’s disease experience increasing difficulty with executive control such as poorer working memory, organization, judgment and planning. 

Sometimes other aggregated proteins are found in Alzheimer’s disease patients at autopsy, including alpha-synuclein and TDP-43, although the roles of these proteins in the pathophysiology of Alzheimer’s disease is only beginning to be understood. 

CLINICAL FEATURES OF ALZHEIMER’S DISEASE

•  Memory Impairment: The earliest feature of typical Alzheimer’s disease involves an impairment of memory.  This is the ability to learn new information and then retain this information for later recall.  Examples of memory difficulty in Alzheimer’s disease include repeating a conversation, asking the same question repeatedly during the course of a day, and disorientation in place and time.  Subsequently, individuals with Alzheimer’s disease can develop impairments in language, visuospatial functioning and executive control. 
•  Language deficits: Patients with Alzheimer’s Disease can exhibit poor word-finding in conversational speech so that speech is empty of content.  There can also be difficulty with understanding words and sentences that others use when speaking with Alzheimer’s individuals.  Reading and writing can become impaired as well – reading can be difficult because of limited recall of the material that was read a few minutes earlier or difficulty negotiating the spatial attributes of a page of text; writing can be difficult because of poor spelling. 
•  Visuospatial difficulties: Visuospatial deficits can include difficulty reaching for and placing objects in a specific location, difficulty finding objects in a complex scene such as a cupboard, difficulty dressing, and getting lost and making incorrect turns even in a familiar environment such as the community or house where the Alzheimer’s individual lives. 
•  Executive deficits: Individuals with Alzheimer’s disease can display poor performance of multistep tasks such as completing a form or managing finances.  There can be poor judgment because of difficulty maintaining several crucial bits of information in mind at the same time required to make the judgment.  Planning involves consideration of multiple bits of information and projecting a proper course of action, and this too can be difficult in Alzheimer’s disease.  There can also be difficulty with selective attention, and this can result in perseveration (getting stuck on a particular idea or response), over-attraction to a particular feature of the perceptual environment (perceptual boundedness), and echoing features of the environment (such as echoing the speech of others, known as echolalia, and mirroring the actions of others, known as echopraxia). 

AMNESTIC MILD COGNITIVE IMPAIRMENT

A prodromal form of Alzheimer’s disease is known as amnestic Mild Cognitive Impairment.  Many conditions can cause age-associated cognitive decline.  Once these other conditions are ruled out, some individuals have only memory difficulty, and a large percentage of these individuals may develop Alzheimer’s disease over several years. 

Stages of Alzheimer’s Disease

Alzheimer’s disease is a progressive disorder of memory and cognition, and we tend to divide the course of the progression into stages.  Many schemes have been developed to characterize the progression of Alzheimer’s disease, but they all hold in common the fact that the rate of progression is not linear.  Instead, the rate of decline in Alzheimer’s disease tends to accelerate through the course of the condition. 

Perhaps the most common staging scheme divides Alzheimer’s disease into three phases.  In the first or early phase, individuals with Alzheimer’s disease can perform most activities of daily living independently, although there are cognitive deficits that limit the efficiency with which these activities can be accomplished. 

In the second or middle phase of Alzheimer’s disease, individuals can perform activities of daily living such as dressing, bathing and toileting collaboratively with the assistance of others.  This may involve a caregiver’s help through verbal prompts or step-by-step instructions, and sometimes the caregiver will have to become more actively engaged in the activity such as help with dressing and toileting since the is having difficulty with the floppy shape and fine motor control needed to manage clothing.  Sometimes this can be very frustrating for the Alzheimer’s individual who is used to performing these activities independently, and there can be frustration in caregivers who are trying to help a loved one.  It is important to recall that individuals with Alzheimer’s disease have difficulty remembering that they are having difficulty with performing a task; their limitations and frustrations are not voluntary, but are a product of a disease that has compromised the functioning of parts of the brain. 

The third or late phase of Alzheimer’s disease is characterized by the individual being totally dependent on others for activities of daily living such as bathing, toileting, dressing, eating and mobility.