Symposium 1999 was a great success! Almost 250 people were in attendance. The day was lovely and the talks by Drs. Lieberman and Jankovic enlightening. At lunchtime we honored cyclists Donna Kos and Walace Teel for their perseverance in riding all the way across the United States for Parkinson’s awareness, and in the afternoon attended excellent workshops on a variety of subjects intended to help improve the quality of life for all. We want to thank everyone who participated, speakers, workshop leaders and attendees for making this a very special day!

Amen!

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Malcolm Stewart, M.D.

Parkinson’s disease (PD) is generally considered a motor disorder with shaking, stiffness, slowness, and difficulty with balance. Additional symptoms may include depression, anxiety and dementia.

Memory may also be affected in PD, either primarily or secondarily from the aforementioned emotional or cognitive deficits. Deficits in memory in PD generally are characterized by a slowness or reduction in the ability for recall (remembering a fact or experience without a stimulus) compared to recognition of the fact, work, or object. Additional memory deficits can be present as well.

Memory is a complex concept, but can be understood in the context of an individual’s ability to utilize his experience to adapt and respond to the stimuli and demands of the environment. Memory is not a homogeneous or monolithic entity but may be divided into various domains. These domains include declarative memory which reflects personal experience; semantic memory which reflects general factual knowledge. Emotional memory and motor skills are additional domains. In PD the learning of new motor skills may be affected. This deficit may impact negatively in situations where a change in vocation is warranted in a person with PD. Declarative and semantic memory are generally preserved in idiopathic PD but may be affected in PD Plus syndromes or Diffuse Lewy Body Disease (DLBD) which may affect cognitive processes which involves cortical rather than subcortical structures in the brain. Memory deficits associated with cortical processes are often combined with deficits of higher cortical function such as language and informational processing.

The process of remembering can be divided into three main parts: 1) encoding, 2) storage and 3) retrieval. In order for the process of remembering to proceed efficiently, however, the individual must be alert and not have distractions which may occur in a situation in which he is either anxious or depressed or has been affected by an anti-anxiety medication such as a tranquilizer or an anti-Parkinson medication such as an anticholinergic which may cause a confusional state. Hallucinations in a clear senorium generally do not cause memory problems and patients may easily recall seeing bugs, people, or animals that were not acknowledged by others around them. In a confusional state, however, the patient generally will not recall what has transpired recently although their immediate memory is still intact. Confusional states usually affect the encoding process. If the memory can be retained for more than two to five minutes (short term memory), then the process of transfer to long term memory may occur. The retrieval of memory from storage is slow in PD as is noted in the differential performance of recognition compared to recall. This slowness of retrieval is also affected by a decrease in working memory capacity.

The various processes of memory involve different parts of the brain. The short term memory involves both the temporal lobe and the frontal lobe which is important for working memory and the ability to process on line what should be remembered. This working memory is influenced by the subcortical dopamine projections from the basal ganglia to the frontal lobes. Emotional memory centers in the limbic system which is one of the oldest structures of the brain and can influence memory retention by cortical systems. Motor skill memory involves both the basal ganglia and the cerebellum which are subcortical structures. In PD the basal ganglia through various dopamine projections can affect various memory processes. Involvement of the basal ganglia may affect the learning of new skills in PD. This may be ameliorated in part by replacement of dopamine.

In PD, various symptoms may be associated with a decrease in memory. For instance, a loss or decrease in the sense of smell may be both an early symptom of PD as well as having an association with a decrease in memory function. A loss of smell has been noted in other conditions in which there is a decline in intellectual functioning and decrease in memory such as Alzheimer’s Disease, Huntington’s Disease and in schizophrenia. Various tests are being developed to quantitatively assess the sense of smell as an early predictor of conditions such as PD and hopefully intervene at an early stage of the illness to try to prevent the progression of the illness. Other motor symptoms have been associated with a decrease in intellectual functioning and a decrease in memory. For instance, patients with PD who have a gait disability are at more risk for difficulty with memory than those with a tremor. Patients with eye movement problems such as seen in progressive supranuclear palsy (PSP) are also at more risk for decreased memory. Those patients with spasticity seen in conjunction with apaxia as seen in corticobasal ganglionic degeration are at more risk for memory difficulties.

The pharmacology of memory is complex. There are several neurotransmitters which are involved in the memory process. One which is important for the hippocampal formation in the temporal lobes is acetylcholine. With the anti-Parkinson medications which include the anticholinergic agents, short term memory can be compromised. The acetylcholinesterase inhibitors such as donepizel which have been used for the treatment of Alzheimer'’s Disease can sometimes be used in DLBD to help with the memory. Norepinephrine has also been implicated with memory and the beta blockers which block adrenaline can affect memory. Glutamate is important for stimulation of memory and medications which block the NMDA glutamate receptors can adversely affect memory. Serotonin can also play a role in memory. Finally, as mentioned above, the dopamine system working subcortically can affect the working memory in the frontal lobes.

In summary, memory can be involved inpatients with Parkinsonism in a number of ways. There is a spectrum if involvement. Understanding the complex interactions involved in the memory process, the various Parkinson symptoms and the pharmacology of these interactions will lead to more effective therapeutic modalities and approaches.

Within the spectrum of Parkinsonism, there are a number of entities that can present or develop memory difficulties which are more extensive than the slowness or impairment of recall noted in regular PD. The amyotrophic lateral sclerosis-Parkinson-dementia complex which was described from Guam has Parkinson features as well as decreased memory. Alzheimer’s Disease, a cortical disorder, has predominantly memory and cognitive problems but, also has Parkinsonian features, predominantly rigidity and akinesia. The frontal temporal dementia with Parkinson features associated with chromosome 17 has difficulties with memory and Parkinsonism. Finally the patients with motor system atrophy including Shy-Drager syndrome, striatonigral degeneration, and olivo-pronto-cerebellar degeneration are at more risk for memory problems. In addition, those patients with DLBD who have problems with visual hallucinations and alternating levels of alertness are more at risk for memory problems.

The pharmacology of memory is complex. There are several neurotransmitters which are involved in the memory process. One which is important for the hippocampal formation in the temporal lobes is acetylcholine. With the anti-Parkinson medications which include the anticholinergic agents, short term memory can be compromised. The acetylcholinesterase inhibitors such as donepizel which have been used for the treatment of Alzheimer'’s Disease can sometimes be used in DLBD to help with the memory. Norepinephrine has also been implicated with memory and the beta blockers which block adrenaline can affect memory. Glutamate is important for stimulation of memory and medications which block the NMDA glutamate receptors can adversely affect memory. Serotonin can also play a role in memory. Finally, as mentioned above, the dopamine system working subcortically can affect the working memory in the frontal lobes.

Houston Endowment Inc.

Isla Carroll Turner Friendship Trust

Dr. Abraham Lieberman

Medtronic Neurological

Honorariums

In Honor of Helene Cruikshank

Patty & Bob Cruikshank

Mr. & Mrs. Henry Peters

Rhetta Davis

Kyle & Alicia Krouse

Douglas & Sue Maclay

L Ann & Keith Short

Julie & Albert Smith

Memorials

In Memory of Eric Ashworth

Mr. & Mrs. H. E. Lawyer

In Memory of Wayne Bailey

Wanda Emery

In Memory of Dorothy Hyde Bell

Jim Blair

D’Ann Marro

Ellen Wilson

Jed Young

In Memory of H. Keith Bogan

Mr. & Mrs. Robert L. Avinger

Manzanita Alliances, Inc.

Vicki & Jeff Furlong

Marguerite Nichols

Keith & Patty Miller

Mr. & Mrs. Donald E. Paape

Personnel Division, Railroad Commission

In Memory of Clay Chiles

Duane Geis

In Memory of Gloria Currie

Gwindell H. Albritton

Carroll & Wilda Andrews

Bill & Karlene Askins