IPA Bulletin
Recent Advances - Volume 16, Number 1
John O'Brien and Bob Barber
While detailed descriptions of frontotemporal dementia have been available
for some time, consensus diagnostic criteria have not. Such criteria have now
been proposed (Neary et al., Neurology 1998;51:1546-1554). Core and supportive
features are proposed for three syndromes: (i) frontotemporal dementia, (ii)
progressive non-fluent aphasia and (iii) semantic aphasia and associated
agnosia. Such criteria should facilitate wider clinical recognition of these
disorders and prompt further research into their relationship with
neurodegenerative diseases.
Standard teaching that neurones in adult humans cannot divide is
challenged by a study by Eriksson et al., (Nature Medicine 1998;4:1314-1317),
who, using post-mortem tissue from human hippocampus, found evidence of the
existence of new neurones, which had generated from cells in the dentate
gyrus. However, the study could not determine whether the new neurones were
functionally active.
An historical perspective on age-related disorders is provided by Barak
and Achiron (Ageing and Mental Health 1998;2:275-278), who provide an account
of the description of age-related disorders in the Bible. In addition to
physical changes and sensory impairments, age-related disorders such as stroke
and declining cognitive function are well described, as are other age-related
changes in initiative, drive, and sexual functioning. The authors suggest
there is evidence that Biblical writers were well aware of the two classic
disorders of old age, depression and dementia.
While according to the Bible, Methuselah lived to be 969, fruit flies have
a much shorter life span (approximately six weeks). However, a report by Lin
et al, (Science 1998;282: 943-945) finds that a mutation in a single gene
confers a 35% increased life expectancy compared with normal fruit flies under
conditions of stress. The gene involved appears to code for protein involved
with signal transduction, which may modulate both stress response and life
span. It is, however, not clear whether Methuselah had the same gene!
The causes of cognitive impairment in chronic schizophrenia remain
unclear. In a neuropathological study, Dwork et al (American Journal of
Psychiatry 1998;155:1536-1543) compared neuropathological changes in
schizophrenic subjects with definitive cognitive impairment to those without
impairment, as well as to patients with Alzheimer's disease (AD) and those
with chronic mood disorders. While supporting previous research showing that
most cases of cognitive impairment in schizophrenia could not be attributed to
concurrent AD, the authors did find an association between mild Alzheimer-type
pathology and definitive cognitive impairment. This relationship was specific
to schizophrenia, as it was not seen in patients with chronic mood disorders.
The authors conclude that enhanced sensitivity to the effects of aging on the
brain may be a manifestation of diminished cognitive reserve in schizophrenia.
The common clinical view that relocation of patients has an adverse effect
on mortality is given some support by Jackson and Whyte (International Journal
of Geriatric Psychiatry 1998;13:836-839), who studied the outcome of
inpatients following a hospital closure. Results confirmed a slight excess of
deaths during and immediately after hospital closure. However, no long term
effect on mortality was seen, suggesting that the hospital closure and
associated move may have "brought forward" the deaths of some residents while
not increasing mortality in the longer term.
Eating disorders in dementia are common but poorly studied. Keene and Hope
(International Journal of Geriatric Psychiatry 1998;13:700-706) investigated
the natural history of hyperphagia and other eating changes in 99 people with
dementia. They found persistent hyperphagia in a quarter of the sample, with
onset predominantly in the middle stages of dementia, although the symptom
could occur at any stage of the illness. It was generally persistent, lasting
for a median of 16 months, and was not significantly related to age, sex or
type of dementia.
The efficacy of tacrine and gingko biloba in AD was examined in two
meta-analyses. Qizilbash et al. (Journal of the American Medical Association
1998;280:1777-82) analyzed 12 clinical trials using tacrine (n=1984; duration
3-36 weeks; dosages varying from 20 to 160mg/day) and concluded that treatment
had a small but significant positive effect on cognitive performance and
global clinical improvement, but not on functional autonomy. Oken et al.
(Archives of Neurology, 1998;55:1409-15) reviewed the efficacy of ginkgo
biloba on cognitive function, though only 4 of the 57 trials surveyed met all
their inclusion criteria. From these studies (n=212) they concluded that there
was a modest but significant effect of 3- to 6-months treatment with 120 to
240mg of gingko biloba on cognitive function, equivalent to a 3% difference in
the ADAS-Cog test.
Huntington's disease is linked to an increased prevalence of criminal
behavior in males but not females, according to a study from Denmark (Jensen
et al., Journal of Neurology, Neurosurgery and Psychiatry 1998;65:467-71). The
crimes were usually minor in nature: drunk driving was the most frequent
offense. The authors suggested that these behaviors resulted from the combined
effect of personality changes and depressive reactions associated with alcohol
misuse.
A small regular amount of alcohol may, after all, be beneficial. In a
large prospective study of elderly people (n=16,304, aged 50 years or more,
mean follow-up11.5 years) Grønbæk et al. (Age and Ageing 1998;27:739-44) found
light drinkers (1-6 drinks per week) had a lower mortality than both heavy
drinkers (>28 drinks per week) and abstainers.
The need for effective management of non-cognitive symptoms of dementia
was the topic of an important study by Devanand et al. (American Journal of
Psychiatry 1998; 155:1512-20). Completing a randomized, placebo-controlled,
dose-comparison of haloperidol for psychosis and disruptive behaviors in AD,
they found haloperidol in doses of 2-3 mg/day was more effective than either
low-dose (0.50-0.75 mg/day) or placebo. Careful dose titration was
recommended, given the high incidence of extrapyramidal side effects (20% of
those receiving 2-3mg/day).
The psychological impact of stroke was emphasized in a study by
Pohjasvaara et al. (Stroke 1998;29:2311-17). Forty percent of post-stroke
patients experienced a depressive disorder (26% major depression, 14% minor
depression) especially those with increased functional impairment and a past
history of depression. The authors highlight the need for close psychiatric
liaison and active treatment in post-stroke rehabilitation.
The relationship between operations under general anesthesia and cognitive
impairment was investigated in two recent contrasting studies. In a large
retrospective population-based study (n=1257, age range 24 to 86 years),
Dijkstra et al. (Journal of the American Geriatrics Society 1998;46:1258-65)
failed to find an association between a history of operations under general
anesthesia and age-related cognitive decline. Marcantonio et al. (American
Journal of Medicine 1998;105:380-84) examined the association between
intraoperative factors and the development of postoperative delirium. The most
important risk factor related to the development of cognitive impairment was
postoperative hematocrit. It remains to be determined whether controlling the
hematocrit (above 30%) reduces the incidence of postoperative delirium.
Understanding the relationship between vascular risk factors and cognitive
impairment was examined in two epidemiological studies in the Journal of the
American Geriatrics Society. Scott et al. (1998;46:1217-22) failed to find an
association between cognitive function and non-insulin-dependent diabetes
mellitus and impaired glucose tolerance in 1,509 community-dwelling subjects
aged 55 years and over. In contrast, Cacciatore et al. (1998;46:1343-48)
reported an association between congestive heart failure and cognitive
impairment in 1,339 subjects aged 65 and over.
The role of placebo-controlled trials in the symptomatic treatment of AD
was debated in a series of articles in the Archives of Neurology (Farlow,
1998;55:1396-98; Karlawish et al., 1420-24; and Knopman et al., 1425-29). The
discussions, prompted by the availability of antidementia drugs, analyze the
arguments for and against placebo-controlled and active drug-controlled
studies in AD.
Drs. John O'Brien and Bob Barber are the Research
Editors of the IPA Bulletin. They welcome readers' comments via
e-mail (J.T.O'Brien@ncl.ac.uk) or
fax (+44 191 219 5040). John O’Brien
also is Deputy Editor of the IPA Bulletin.
