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(Aghan & Burke)
Multiple Sclerosis III
Parkinson's Disease IV
Visual Form Agnosia
Cerebral Palsy IV
(Labbadia & Taplin)
Multiple Sclerosis IV
Cerebellar Ataxia II
Huntington's Disease III
Smooth Pursuit II
Progressive Supranuclear Palsy
Postural Control II
Parkinson's Disease III
Huntington's Disease II
Phantom Limb III
Vestibular Rehabilitation and Concussion
Cerebral Palsy III
Multiple Sclerosis II
Myofascial Referred Pain
Seizure - Cortical Related
Visual Cortical Neurons
Learning to Dance - Observation vs Action
Restless Leg Syndrome
Grand Mal Seizure
Cerebral Palsy II
Duchenne Muscular Dystrophy
Basal Ganglia II
Saccadic Eye Movement
Shaken Baby Syndrome
Parkinson's Disease II
Alcohol & Cerebellum
(Leach & McManus)
Phantom Limbs II
Cerebellum & Motor Learning
Motor Unit Adaptation
Aging Nervous System
Dance & the Brain
Enteric Nervous System
Golgi Tendon Organs
Vestibular Occular Reflex
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder resulting from attacks on the brain’s nerve cells. Although this disease can be diagnosed at any age, it is most commonly recognized later in life. It is
characterized by the presence of abnormal protein aggregates in neurons and extracellular space of the central nervous system (CNS). The causes of
Alzheimer’s are unknown, but the “amyloid cascade hypothesis” is the most widely accepted and discussed theory. The strongest research in support of this hypothesis suggests that a genetic mutation leads to excessive production of a small peptide, amyloid β-protein (Aβ). Large Aβ fibers create lesions—neurofibrillary tangles and senile plaques—that obstruct the pathways of neural signals. Such interferences lead to complications in axonal transport from one neuron to the next, most often associated with major memory impairments. These lesions can also contribute to movement and motor control disorders [1,2,7].
Progression of Alzheimer's Disease:
: Patient becomes increasingly forgetful and experiences short term memory loss, disorientation of time and space,
: Patient is now suffering from both short term and remote memory loss, clumsy movement, decreased muscle control,
ideomotor and ideational apraxia
: Patient is now suffering more severe dementia symptoms, decreased communication abilities,
apraxia resulting in one
, minimal motor control, and behavioral problems [3,7].
Amyloid Cascade Hypothesis:
amyloid-β protein (APβ)
, the main component of senile plaques, is the direct cause of AD pathology; neurofibrillary tangles, cell loss, vascular damage, and dementia are the results of such deposition and are therefore indirect causes. AβP is a peptide product of the larger
amyloid precursor protein (APP)
. APP proteolysis leads to AβP deposition when APP is inserted into the cytoplasmic membrane and cleaved within the AβP sequence, resulting in fragments lacking intact AβP. These fragments cannot result in amyloid deposition. Mutations within the APP have empirically shown to cause familial AD. They inhibit the breakdown of a COOH-terminal fragment of APP that contains AβP, alter the anchoring of APP in the cell membrane, and/or stabilize AβP-containing amyloidogenic fragments within lysosomes. The
amyloid cascade hypothesis
claims that AβP, or APP cleavage products containing AβP, are neurotoxic and can lead to neurofibrillary tangles or cell death. For this to lead to AD, AβP must be generated as an intact formation, either
by accumulation of AβP itself or as an AβP-containing fragment of APP, and this molecule must facilitate or cause neuronal death and tangle formation. The overall result is neuron disconnection, leading to cell death, brain shrinkage, and loss of function in many areas[5,8].
Formed when proteins in the neuron of a cell membrane are processed differently than in a normal, healthy brain. Normally, the enzyme alpha-secretase cuts APP to release a fragment. Gamma secretase, a second enzyme, also cuts APP in a different place and releases a second fragment. The two fragments together benefit the neuron. In AD brains, the first cut, normally done by alpha-secretase, is made instead by beta-secretase. This cut, along with one made by gamma-secretase, release shorter fragments of APP called beta-amyloid fragments. It is when many of these fragments clump together that they become toxic and interfere with neuronal functioning. As they increase in size they become insoluble and constitute as plaques[8,9].
These fibers are formed when
is modified. In normal brains, tau stabilizes structures critical to the cells internal transport system. Nutrients and other necessary components of these cells are carried along microtubules to all parts of the neuron. In AD
brains, tau is abnormal and separates from the microtubules, causing them to fall apart. The strands that detached from the microtubules combine and form tangles in the neuron, disabling the transport system and disabling the cell[8,9].
Video - Plaques & Tangles
Apraxia & Alzheimer's:
is defined as difficulty making voluntary gestures in the absence of motor or sensory inputs. Alzheimer’s patients most often suffer from ideomotor apraxia or ideational apraxia.
Patients with AD who experience apraxia often have been associated with unilateral or bilateral cortical atrophy and diminished activity in parietal regions. These findings indicate parietal lobe hypoperfusion, the inadequate perfusion of tissue within the parietal lobe that results in less than necessary levels of oxygen and nutrients, leads to cell death. Although it is less frequent, apraxia can also be the result of right hemispheric lesions, which suggests that visuokinaesthetic engrams containing spatial and temporal representations may be represented either bilaterally or in the non-dominant hemisphere [4,8].
Basal Gangila in Apraxia:
The motor and premotor cortices project to the basal ganglia along with the parietal cortex. These areas are interconnected and make up the
. These circuits are involved in sensorimotor integration or in translation of sensory input into information for the production of movement. Which circuit is activated depends on the activity wanting to be performed is new or learned, and the complexity of the movement overall. Dysfunction of the basal ganglia can lead to errors of the praxis and result in apraxia. Lesions in areas such as the putamen, globus pallidus internus, caudate, and substantia nigra have all empirically been suggested to play a role in the development of apraxia in AD .
Ideomotor Apraxia (IMA):
is the inability to imitate a gesture or perform a movement on command due to difficulty in translating the concept of a motor sequence into the correct motor action. This may not be immediately perceived by the AD individual as it predominantly undermines gestures when they are asked for in a theoretical setting. Anatomically diverse lesions in the left hemisphere tend to cause IA; they typically involve parietal association areas and white matter bundles that serve to connect frontal and parietal association areas. Less common, but still significant, are premotor and supplemental motor cortex lesions that involve the basal ganglia and/or thalamus [6,8].
Ideational Apraxia (IA):
is a failure to mentally evoke the gesture associated with an object, such as difficulty carrying out complex goal-directed activities, even when the goal is understood. Both IMA and IA severity are directly related to the rate of progression of the Alzheimer’s disease. Damage causing IA is typically thought to involve left parieto-occipital and parietotemporal regions [6,8].
Agnosia & Aphasia in Alzheimer's:
is defined as the inability to recognize objects, people, sounds, shapes, or smells. It can take on three different forms--visual, auditory, or tactile--and is associated with deficits in neuronal-axonal transport across visual processing areas and sensorimotor areas of the brain. It typically onsets in the second stage of Alzheimer's disease, categorized as the stage of confusion .
is the loss of ability to express or understand speech as a result of damage in the frontotemporal areas of the brain. This often begins in the early stages of AD and is one of the more frustrating aspects for the patient .
Video - Effects of Agnosia
While there is no known cause of Alzheimer's disease, the amyloid cascade hypothesis offers the most insight to neurological processes and dysfunctions that can lead to the symptoms of the disease. Reduced axon transport is caused by more of amyloid-β protein being produced and released. This leads to lesions in the brain composed of proteins that block the pathways (plaques and neurofibrillary fibers) in the extracellular space of the brain. Such deficits can lead to memory loss, confusion, apraxia, agnosia, and aphasia. There is no cure for Alzheimer's, but there are possible treatments to reduce the effects of the secondary diseases that impair movement and enhance the quality of life for a patient.
Glossary of Terms:
the inability to recognize objects, people, sounds, shapes, or smells.
Alzheimer’s disease (AD)
: chronic, progressive neurodegenerative disorder resulting from attacks on the brain’s nerve cells, usually leading to memory loss, motor control dysfunction, and language deficits.
Amyloid-β protein (APβ):
the main component of senile plaques, produced when APP is sliced incorrectly.
Amyloid precursor protein (APP):
larger piece protein that amyloid-β protein derives from.
the loss of ability to express or understand speech as a result of damage in the frontotemporal areas of the brain.
failure to mentally evoke the gesture associated with an object, such as difficulty carrying out complex goal-directed activities, even when the goal is understood.
inability to imitate a gesture or perform a movement on command due to difficulty in translating the concept of a motor sequence into the correct motor action.
fibers formed when tau protein is modified.
circuits involved in sensorimotor integration or in translation of sensory input into information for the production of movement.
formed when proteins in the neuron of a cell membrane are processed differently than in a normal, healthy brain.
stabilizes structures critical to the cells internal transport system.
Slowly Progressive Apraxia
Apraxia in Movement Disorders
More on Aphasia
1. Which of the following is not involved in the Amyloid Cascade Hypothesis?
b) amyloid-beta protein
2. Apraxia is best defined in which of the following ways?
a) the inability to express of understand speech
b) difficulty making voluntary gestures in the absence of motor or sensory inputs
inability to recognize objects, people, sounds, shapes, or smells
translation of sensory input into information for the production of movement
3. Which symptom of Alzheimer's Disease most commonly has the earliest onset?
a) short term memory loss
c) ideomotor apraxia
d) ideational apraxia
4. Tau protein clumps together to form insoluble patches called senile plaques, leading to disrupted axon-transport systems.
5. Amyloid-β Protein is the larger fragment from which Amyloid Precursor Protein is derived from.
6. The basal ganglia contains parietofrontal circuits that are involved in sensorimotor integration or translation of sensory input into information for production of movement.
7. The main reason Alzheimer's disease leads to motor control disorders is due to the disrupted axonal transport that occurs.
8. Explain the differences between ideomotor apraxia and ideational apraxia.
9. Compare and contrast the formation of senile plaques and neurofibrillary fibers.
10. Describe the progression process of Alzheimer's disease as a whole. Include which symptoms occur at which stages.
 Buchman AS, Bennett DA. Loss of motor function in preclinical Alzheimer's disease.
Expert Review Neurotherapy
11(5): 665-676, 2011.
 Chapman SB, Highley AP, Thompson JL. Discourse in fluent aphasia and Alzheimer's disease: Linguistic and pragmatic considerations.
Journal of Neurolinguistics
11: 55-78, 1998.
 Crystal H, Marks JW, Stoppler MC. (2015). Alzheimer's Disease [Online]. MedicineNet.
[3 December 2015].
 Green RC, Goldstein FC, Mirra SS, Alazraki NP, Baxt JL, Bakay RA. Slowly progressive apraxia in Alzheimer's disease.
Journal of Neurology, Neurosurgery, and Psychiatry
59(3): 312-315, 1995.
 Hardy JA, Gerald A. Alzheimer's Disease: The Amyloid Cascade Hypothesis.
184: 256, 1992.
 Lucchelli F, Lopez OL, Faglioni P, Boller F. Ideomotor and Ideational Apraxia in Alzheimer's Disease.
International Journal of Geriatric Psychiatry
8(5): 413-417, 1993.
 N/A. (2015). About Alzheimer's Disease [Online]. Alzheimer's Foundation of America.
[3 December 2015].
 Zadikoff C, Lang AE. Apraxia in movement disorders.
128: 1480-1497, 2005.
 Plaques and Tangles:
[10 December 2015].
[10 December 2015].
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