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Few Treatments, Poor Prognosis for Amnesia

April 13, 2012 — Amnesia is a multifaceted disease with several variants, some of which are associated with a poor prognosis, note coauthors of a new comprehensive review of amnestic disorders.

“The main message of the paper is that memory is not a unitary concept or unitary neurocognitive function, and conceptual understanding of the division of memory along the time and content dimension is crucial for clinical understanding, diagnosis, laboratory and medical workup, treatment and follow up of amnesic disorders as well as for rigorous research,” first author Hans J. Markowitsch, PhD, of the University of Bielefeld, Germany, told Medscape Medical News.

Dr. Markowitsch and coauthor Angelica Staniloiu, MD, of the Alfried Krupp Institute for Advanced Study in Greifswald, Germany, searched PubMed, Medline, and Scopus to get an overview of amnesia research from the past 5 years, and their findings are published online April 13 in the Lancet.

A Research Passion

For more than 3 decades, Dr. Markowitsch has focused his research on memory and memory disorders. “Although I tackled other fields of neuroscience, my main research passion has revolved around memory and its disturbances,” he said.

Over the years, he has witnessed an “increasing flow” of articles devoted to research in amnesia and memory, probably related to the availability of modern brain-imaging techniques. He has also seen “changes in the conceptualizations of memory systems and theoretical frameworks guiding memory research.”

“I gladly agreed to undertake, in collaboration with Angelica Staniloiu, the challenges of conducting this review and writing a synthesis of research data from the field of amnesic disorders in order to foster a better communication and application of knowledge between clinicians — physicians, neuropsychologists — and researchers of memory,” Dr. Markowitsch told Medscape Medical News.

In their review, the authors note that memory disturbances often occur after brain damage and can also be associated with psychiatric illnesses. The term amnesia, they say, is mainly used in 2 ways.

First, it is used to describe any severe memory impairment, irrespective of cause. Second, it is used “in line with the traditional view” that amnesia occurs in the absence of other substantial cognitive impairments and is restricted to specific disorders having a core feature of memory impairment that is not due to dementia or delirium and represents a decline from a previously attained functional level.

“Global Amnesia” Outdated

Amnesia in the strict sense — a total and exclusive loss of the ability to store new information consciously and on a long-term basis, or to retrieve long-term stored information consciously — is “rarely found,” the authors point out. Their review includes a panel naming and describing 27 variants of amnesia.

Endel Tulving, OC, PhD, FRSC, FRS, professor emeritus, University of Toronto, in Ontario, Canada, who reviewed the article for Medscape Medical News, said that the paper contains “the most complete listing of varieties of amnesic syndromes” that he has seen.

A copy of it ought to be in the desk drawer, if not on the wall, of every physician who sees patients with neurological or other brain/mind related complaints.

“A copy of it ought to be in the desk drawer, if not on the wall, of every physician who sees patients with neurological or other brain/mind related complaints.” Dr. Tulving is an experimental psychologist and cognitive neuroscientistist who has conducted pivotal work on human memory.

Topping the list is “global amnesia” — which the authors say is “an outdated diagnosis that implies total memory loss (it is outdated because in most amnesiacs implicit processing via the procedural and priming systems is usually preserved),” they write.

Other variants include the following:

  • anterograde amnesia: the inability to acquire, store, or retrieve new information long-term and consciously after a memory-impairing incident;
  • retrograde amnesia: the inability to consciously reactivate information that was stored long ago;
  • partial amnesia: lacunar amnesia; memory loss restricted to particular kinds of information or life epochs; and
  • material-specific amnesia: naming impairment with respect to objects or materials.

“Amnesic disorders could be etiologically linked to a variety of factors,” Dr. Markowitsch commented. Dissociative amnesia, for example, is a psychiatric disorder characterized by an inability to recall personal information that is underlain by the psychological mechanism of dissociation. “Dissociative amnesia,” Dr. Markowitsch noted, “has been linked to psychological stress or trauma in various cultures, and the use of sophisticated brain imaging began to shed light on its neural correlates.”

“Transient global amnesia” is also on the list. It develops suddenly, usually in adults older than 60 years, and is triggered by physiological or psychological factors, the authors note. Its course is benign because it typically disappears within a day, they say, although slight memory deficits may persist for months, especially if anxiety or depression are present, they say.

Effective Treatments “Scarce”

“Assessment of amnestic disorders includes anamnesis and medical, laboratory, and occupational-therapy evaluations,” the authors say, adding, “Neuropsychological testing is invaluable to objectively establish the nature and severity of the memory impairment, to quantify longitudinal changes, and to distinguish between amnesias of different causes and feigned amnesia.” The researchers provide a flow diagram on assessment in supplementary material available online.

The researchers note that although transient global amnesia and a “few” other amnestic disorders are associated with a good prognosis, “prognosis remains poor” in patients with some variants, especially variants involving complete bilateral damage to medial temporal lobe, diencephalon, or basal forebrain.

Data on the value of pharmacological treatment for amnestic disorders are “scarce” and come from uncontrolled studies with small numbers of participants. “Thus, no evidence-based psychopharmacological or somatic treatments are known to be definitively effective at reversing memory impairments or deficits in amnestic disorders,” the authors note.

“This review, according to the authors, was meant to bring interested readers up to date on what has been happening in the field of memory disorders and where we are now. It has clearly succeeded in doing so,” Dr. Tulving told Medscape Medical News. “It shows clearly how research on memory disorders can be, and a good deal of it now is, guided by empirical findings and concepts in mainstream cognitive neuroscience,” he added.

Going forward, Dr. Markowitsch said, “Developing adequate treatments for amnesic disorders is very much needed and may benefit from application of discoveries in the field of molecular biology, genetics, and epigenetics.”

“Identifying which psychological processes (eg, consolidation vs retrieval) are involved in various amnesic disorders and mapping these processes onto specific brain areas are also an area of further research,” he added. “The prognosis and long-term course of amnesic disorders etiologically linked to psychological factors (eg, dissociative amnesia) are other topics in need for further studying. In addition, it is important (especially for the practice of forensic psychiatry or psychology) to further develop and improve the methodology and instruments for differentiating feigned from true amnesia.”

A Rarity

“I give this review a high mark,” Dr. Tulving said. “The article is a rarity. Memory today is one of the topics of great interest in neuropsychology and cognitive neuroscience,” he said, yet there have been “surprisingly few general reviews written on the topic.”

“The review is beautifully balanced,” Dr. Tulving added. “The authors have no axe to grind or their own pet theories to push. In rapidly developing contentious fields, such as neuropsychology and cognitive neuroscience, the absence of bias is another rarity that deserves attention.”

The review was funded by the University of Bielefeld and grants from the Cluster of Excellence Cognitive Interaction Technology (CITEC), EU (NEST programme; Eyewitness Memory), the German Research Council, and Alfried-Krupp Stiftung, Greifswald. The authors and Dr. Tulving have disclosed no relevant financial relationships related to this work.

Lancet. 2012. Published online April 13, 2012. Abstract

Filed Under: Amnesia and Memory

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