Chameleon Dementias
In 1976, a two-page editorial in the journal Archives of
Neurology (now JAMA Neurology), penned by the neurologist Richard Katzman,
transformed Alzheimer’s disease into an overnight sensation. The title of the
paper emphasized the aim “The Prevalence and Malignancy of Alzheimer Disease: A
Major Killer.” With the stroke of a pen, Alzheimer’s disease become the 4/5th
killer in the world.
Katzman’s secret was simple. By eliminating the distinction
between Alzheimer’s disease and senile (of old age) dementia Alzheimer’s
disease become a major disease. Since “age” was the only reason that
Alzheimer’s disease was defined as separate from senile (of old age) dementia—by
Alois Alzheimer’s supervisor, Emil Kraepelin in 1912—this must have been
difficult. But eliminating Alois Alzheimer’s definition proved surprisingly
easy because there was no distinction in the first place. Katzman’s article by
acknowledging this false distinction generated a lot of political capital in supporting
the mission of the newly ordained National Institute on Aging. But if the
reason for defining Alzheimer’s disease was wrong, what else is wrong with our
interpretation of the disease?
And a hundred years later we still have no idea what causes
dementia. Katzman threw us back into the past, and now, building upon this
political tactic, researchers have again revisited the same issues that
occupied them more than a hundred years ago.
History
From ancient Egyptians to the time of Alois Alzheimer in
1900s, dementia was known and rightfully, feared. Early Egyptians first
document cases of what could be dementia more than two thousand BC. In a
literary text from the beginning of the 2nd millennium BCE, a poem that damning
description of aging is placed in the mouth of the embalmed city administrator
and first historian Ptahhotep:
Senescence has come, elderliness
descended.
Weakness has arrived,
helplessness returns.
As one spends every
night becoming more childish.
Eyesight has
diminished, the ears become deaf.
Strength is perishing
from my heart’s fatigue.
The mouth has fallen
silent and cannot speak.
The heart is exhausted
and fails to remember yesterday.
Bones ache because of
length (of years).
Good has become evil.
All taste is gone.
What old age does to
people,
Is evil in every
respect
The nose is blocked
and cannot breathe
from weakness in
standing and sitting.
Throughout history, the diagnosis of dementia was confused
with many other disorders. The cause was explained through the interpretative
prism at the time. From the ancient Egyptians who conceived of dementia as a
disease of the heart, to the middle ages where evil spirits invaded the body.
Social norms and scientific fads at the time dictated how disease is explained,
and dementia was no different. What was important in changing this was how we
categorized diseases, especially dementia. And this formed in earnest in the
late 1700s when French physicians took a more formal and objective approach to
describing dementia.
Early French
Scientists
We pick up the story in 1797 with the French psychiatrist,
Philippe Pinel (1745-1826), who coined the term démence—deriving from the Latin de
meaning "out of" and mens
meaning "the mind." One of Pinel’s patients was a woman who over a
period of just a few years, lost her memory, speech, and her ability to walk or
use common household objects. After Pinel autopsied her brain. he described the
woman’s brain as full of fluid and having dramatically shrunk to a third of
normal size. In retrospect, Pinel’s patient is likely to have had normal
pressure hydrocephalus (NPH). To this day NPH results in more than 9-14% of
those admitted to nursing homes to be erroneously diagnosed with dementia. But
despite this error, what was significant for the time was the identification of
dementia as a biological disease.
After Pinel made this biological connection then it was up
to another Frenchman, Jean Etienne Dominique Esquirol (1772-1840), to state
more precisely the different types of dementias. Esquirol clearly distinguished
dementia from mania—psychoses—and from mental deficiency. He also distinguished
between acute, chronic and senile (of old age) dementia. His explanation is
important as well since the different causes related to their distinguishing
feature rather than their expression (i.e. they might be expressed in the same
way). Acute dementia was short-lived, reversible, and followed a fever,
haemorrhage or metastasis; chronic dementia was irreversible and caused by
masturbation, melancholia, mania, hypochondria, epilepsy, paralysis and
apoplexy; lastly, senile dementia resulted from old age, and consisted in a
loss of the faculties of the understanding. Separating the observations of
dementia into distinct categories based on what was assumed to be the cause,
allowed for a more specific understanding of dementia. Although for senile
dementia “age” was a good enough reason.
Pinel and Esquirol’s view that dementia was caused by many
factors, was in contrast with the explanation used by a contemporary French
physician Antoine Laurent Jessé Bayle (1799–1858). Bayle view was that dementia was caused by an
organic disease that caused swelling in the brain. Unknown at the time, Bayle
was referring to the effect of long term syphilis infection. Bayle also
observed that dementia progresses and becomes increasingly more severe. This
interpretation was so influential at the time that dementia was also called
Bayle’s disease and dementia paralytica.
By the late 1800s, French physicians already started
engaging in a discussion about different types of dementia and identifying
senile dementia, the initial observation of a biological cause of dementia, and
the progressive nature of the disease.
German Scientists
While this discourse was going on, there was a parallel push
to study dementia in Germany. The German scientists had a slightly different
approach, including attracting a different name. Senile dementia was named as Presybyophrenia—from the Greek Presby meaning “old” and phrenia meaning of the “mind”—dementia
of older age. This term was coined by the German physician Karl Ludwig Kahlbaum
(1828–1899). With his associate Ewald Hecker (1843–1909), Kahlbaum introduced a
classification system that applies terms that described the disease as
expressed depending on biological developments in the body. These German
physicians concentrated on nosology—how diseases are categorized. Their
observations and methods have contributed to how we categorize disease today.
They argued that by grouping mental disorders based on how they
are expressed ignores how the diseases progresses and how it affects the
person. Supporting Pinel-Esquirol-Bayle contention that the cause of the
disease should be the defining feature of the disease. For example, a fever that comes on in a day
and dissipates in a few days is very different from a fever that comes on
slowly and lasts longer. Differences in how a disease progresses and the
eventual outcome as a method of classifying different diseases proved
providential. Kahlbaum and Hecker’s evaluation of earlier classification of
diseases was that physicians were often prejudiced. By making judgements on how
diseases are similar to each other, prevented physicians from gaining useful
insights into its causes and how to address treatment.
There was a convergence between the French and German
physicians at the turn of the 20th century. At the time the final stages of the
bacterial infection of syphilis that results in dementia—neurosyphilis—was
contributing to between 10-24% of all hospitalized mental health patients at
the time. This is what led Bayle to identify physical causes of dementia but
did not know that it was syphilis. In fact, Alois Alzheimer’s
specialization—and how he met his wife, the widow of one of his patients—was as
an expert in treating syphilis. In 1910, Alzheimer already knew of the
connection between syphilis and the plaques and tangles that came to
characterize his disease. This biological cause encouraged further parallels
between an infection and senile dementia.
But both Kahlbaum and Hecker were moving away from
simplistic explanations of diseases. Together with Emil Kraepelin (1856-1926),
who later coined Alzheimer’s disease, these three men also shared a deep
skepticism for the localization of behavior in the brain. Such brain
explorations were becoming very popular during the latter half of the 19th
century. Paul Broca (1824-1880) together with Carl Wernicke (1848-1905) were
leading pioneering work on the localization of brain functions, specifically in
speech. But Kahlbaum-Hecker-Kraepelin had bigger worries than such collegial
competition.
Competition
The 1900s saw an explosion of academic proliferation. Some
of the most famous scientists at the time included: Max Planck (quantum
physics), Albert Einstein (physics), Marie Curie (X-rays), Sigmund Freud
(psychoanalysis), Niels Bohr (physics), Ivan Panlov (medicine/psychology),
Santiago Ramón y Cajal (neuroscience), Franz Boas (anthropology), Wilhelm Wundt
(experimental psychology), Richard J. Ussher and Robert Warren (zoology),
Ferdinand von Zeppelin (aeronautics) among many other. Together with the new
science fiction of H. G. Wells, the early 1900s saw a proliferation of academic
disciplines and new hope for the scientific method.
For the emerging study on dementia and the newly identified
Alzheimer’s disease by Emil Kraepelin there were other considerations.
Primarily there was the perceived (and real) threat that psychiatry was facing
from psychoanalysis and from psychology. The case in point was the story of
Anna O, now known as Bertha Pappenheim (1859–1936), whose psychoanalytic “cure”
created fervor and excitement. An Austrian-Jewish feminist, Bertha Pappenheim
suffered from hysteria—paralysis, convulsions, hallucinations and loss of speech—without
apparent physical cause. Josef Breuer ostensibly succeeded in treating Anna by
helping her to recall forgotten memories of traumatic events. Psychoanalysts
proposed that physical symptoms are often the surface manifestations of deeply
repressed conflicts. At the turn of the 1900s, after centuries of treating
madness as a mystical curse, here was a clear answer and a clear solution.
After distinguishing idiocy, epilepsy and cretinism, the remaining maladies had
the possibility of being psychosomatic. In hindsight, we now know that these
particular case studies—including Bertha Pappenheim—were not cured, and the
likely cause of these expressions of hysteria were biological in nature.
In addition to the new vogue of psychoanalytic models, there
was a complementary interpretation of disease championed by Kraepelin’s own
mentor, Wilhelm Wundt. Kraepelin submitted his thesis on "The Influence of
Acute Illness in the Causation of Mental Disorders" under Wundt, for which
he received his medical degree in 1878.
A year later Wundt founded the first formal laboratory for psychological
research at the University of Leipzig. Wundt and experimental psychologists
promoted the idea that we learn how to behave, including when we are behaving
abnormally, a theory very much in keeping with the psychoanalyst’s view of
disease. At the turn of the century in Germany, psychological theories were
becoming the new norm. Kraepelin and his staff did not approve of this
interpretation of mental illness. Max Isserlin, an assistant to Kraepelin, made
disparaging remarks about psychoanalyses being “complex mythology” which Freud
identified as arguments coming “from the blackest clique in Munich,” referring
to Kraepelin’s clinical staff. Such animosity ultimately lead to Isserlin being
personally expelled by Jung in 1910, from the Congress of the Psychoanalytical
Association in Nuremberg. Despite such obvious animosity, there was an intellectual
challenge as well. While psychologists and psychoanalysts repeatedly believed
that they were gaining ground in understanding mental diseases, what did
psychiatry have to offer?
Kraepelin, a seasoned administrator, was aware of this
constant yearning for answers. Yearnings for a panacea were real. Kraepelin
needed to distinguish psychiatry from the “learning” of the psychologists and
the “unconscious” of the psychoanalysts. In doing so he had to resort back to
the biology of mental illness. Psychiatry could contribute the biological
aspect of mental health.
The contribution of
Biology
Kraepelin (with Eugen Bleuler) gained a different kind of
success by differentiating schizophrenia from a variety of mental
disorders. The 1880 U.S. Census only
distinguished seven categories of mental illness: mania, melancholia,
monomania, paresis, dementia, dipsomania, and epilepsy. Psychosis was
categorized as hysteria, melancholy, mania, and paranoia. Within this morass of
disorders, Kraeplein differentiated between premature (praecox) dementia
(schizophrenia) and ‘manic depression’ as two separate forms of psychosis.
Although schizophrenia was already described as dementia praecox, first in 1852
by the French physician Bénédict Morel and later in 1886 by Heinrich Schule, it
was Arnold Pick in 1891 who defined schizophrenia as a psychotic disorder (hebephrenia from the Greek hebe “young,” and phrenia “mind”). In 1911, Eugen Bleuler revised this idea, renaming
‘dementia praecox’ (premature dementia) as schizophrenia.
Kraepelin reverted back to the earlier French scientists
Pinel-Esquirol-Bayle in arguing for a biological cause to schizophrenia by
anatomical or toxic processes (as yet unknown.) When, on his second attempt,
Alzheimer managed to publish his observations on Auguste Deter, Kraepelin
jumped at the chance to reinforce the biological emphasis of disease by
elevating Alzheimer’s disease as different from senile dementia. As with
schizophrenia Kraepelin was intimating that Alzheimer’s disease is caused by
anatomical or toxic processes which are yet unknown.
Fast forward to 2017, with increasingly powerful biological tools
that are now available we are about to enter this portal that was created more
than a century ago.
Biomarkers
Alzheimer’s disease guidelines published in 2011 by the U.S.
National Institute on Aging and Alzheimer Association, has attempted to define
how biological measures can be usefully classifying mental diseases. As with
the early pioneers Kahlbaum, Hecker, and Kraepelin, a new method is being
devised to better answer the question of what dementia is. Current psychiatric classification of
diseases—Diagnostic and Statistical Manual (DSM-5) and International
Classification of Disease (ICD-10)—are focused on being reliable but are short
on validity. Repeating the conflict between the early German and French
scientists more than a hundred years ago, there is now a shift from surface
expression of the disease to search for the underlying causes, except now we
can measure biological indicators better than in the past.
To enable this biological emphasis, and in contrast to the
DSM-5 and ICD-10, a new classification criterion is being promoted. Research
Domain Criteria (RDoC) is a new classification of diseases initiated by the
U.S. National Institute of Mental Health director Thomas Insel. Insel now works
for Google Life Sciences with a new name: Verily, a for-profit health company.
RDoC argues that mental disorders are biological disorders involving brain
circuits. And the first test of RDoC’s approach is with dementia. Mirroring Bayle’s
1882 contention that inflammation of membranes that surround the brain and the
spinal cord resulted in mental disease, RDoC is following a long line of
psychiatrists looking for biological markers to mental health.
Biological
determinism of dementia.
There are many faults with RDoC’s focus on neural circuits
which excludes research on psychological processes and mechanisms. This is
nothing new and we only have to see the arguments in the late 1800s to
understand these criticisms. For example, Bayle’s colleagues, especially
Esquirol, argued that although there might be correlation there is no
indication of causation. Even if causation can be identified it does not
explain all dementias. And there are other concerns that were voiced earlier on
in the history. Especially by Erich Hoche (1865-1943) on our inability to
accurately identifying mental disease; Karl Birnbaum (1878-1950) on how
disorders are expressed differently by individuals or cultures; Robert Gaupp
(1870-1953) on psychosomatic factors that involve mental, emotional, or
behavioral factors. And of course, we now know that that these criticisms
remain valid to this day. RDoC simple brushes them away, not by ignoring these
factors, but by discounting their influence and importance. It succeeds in
doing this because it is concentrating on dementia.
We still do not know what dementia is. The basic issue is a
catch 22—in order to be able to differentiate diseases we need to understand
their causes and to understand the causes we need to be able to differentiate
it. We must be aware of the history in order to stop this cycle of oscillating
between the false dichotomy of biological vs everything else. Normality is not
simply the absence of pathology. Many symptoms exist on a spectrum or continuum
from mild expressions that might be viewed as variants of normality through to
severe symptoms associated with impairment. One way to escape this conundrum is
to ignore the expression of the disease and to accept the underlying “cause” as
proof. But what RDoC ignores is that there are many biological markers and that
the brain is the most complex entity in the universe. In such circumstance then
you have to approach dementia as a public health issue, where many causes are
present. An approach which RDoC continues to ignore. Could it be because you cannot commercialize public health?
References
Engstrom, E. J. (2016). Tempering madness: Emil Kraepelin’s
research on affective disorders. Osiris, 31(1), 163-180.
Garrett, M. D., & Valle, R. (2015). A New Public Health
Paradigm for Alzheimer’s Disease Research. SOJ Neurol, 2(1), 1-9.
Kendler, K. S., & Engstrom, E. J. (2016). Kahlbaum,
Hecker, and Kraepelin and the transition from psychiatric symptom complexes to
empirical disease forms. American Journal of Psychiatry, appi-ajp.
Kurt, C.S. et al., The Realities of Ageing, Boston, 1990.
Wundt, W. (1881). Wilhelm Wundt to Emil Kraepelin, 23
January 1881. Max Wundt Papers: University of Tübingen Archives, 228, 17.
© USA Copyrighted 2017 Mario D. Garrett
