IPA Bulletin
Recent Advances - Volume 15, Number 1
John O'Brien and Bob Barber
Recent supplements of interest include the September 1997 supplement to
Neurology, which reported the findings of the Consortium to Establish a
Registry for Alzheimer's Disease, and the September 1997 supplement to the
American Journal of Medicine, which summarised the proceedings of a symposium
on "The role of estrogen in the treatment and prevention of dementia." The
results of an extensive 11-year follow-up study to examine the impact of aging
on cognitive functions were published in Acta Neurologica Scandinavica
Supplementum (Laursen P, No. 172, Vol. 96).
Once again the accuracy of death certification in dementia has been
questioned. Thomas et al. (Age & Ageing 26: 401-406) found considerable
underdetection of cases, especially for vascular dementia. Only 49.7% of
patients with vascular dementia had a dementia diagnosis recorded anywhere on
the death certificate, compared with 90.5% for patients with Alzheimer's
disease (AD). The message for studies relying on death certificates for
diagnostic information is clear.
The finding in AD that noncognitive symptoms are frequent yet episodic
has been reinforced by a longitudinal study from New York (Marin et al.,
Journal of the American Geriatrics Society 45: 1331-1338). Three-year
follow-up findings suggested that increasing severity of symptoms at one time
is usually followed by improvement later, and vice versa. The authors argued
for treatment regimes that reflect the temporary nature of these symptoms.
The use of plant extracts in the treatment of dementia continues to be
explored. In this instance (Le Bars et al., Journal of the American Medical
Association 278: 1327-1332) Ginkgo Biloba was the plant, EGb 761 the extract,
and AD and multi-infarct dementia the study group. Compared to the placebo
group, treated patients had modest improvements in cognitive function (as
measured by the ADAS-Cog) after 26 and 52 weeks. Treated patients were more
likely to be considered improved by caregivers, though there were no
differences in the Clinical Global Impression of Change. Adverse events were
no more common in the treated group. EGb 761 is approved in Germany for the
treatment of dementia.
"Aging" was the focus of intense interest in October, with over 100
journals dedicating articles or issues to this topic. These included a special
edition of the American Journal of Psychiatry on geriatric psychiatry,
containing an article by Zubenko et al. (154: 1360-1368) that examined
survival in over 800 elderly patients with organic mental disorders, mood
disorders, and psychotic disorders. After controlling for comorbidity and
demography, all groups had higher mortality rates (SMR of 1.5 to 2.5) than
age-matched controls. Patients with mood disorders were more likely to die
from suicide and, in contrast to previous studies (which have emphasised
cardiovascular and cerebrovascular causes), disorders of the gastrointestinal
system.
In the same edition of the American Journal of Psychiatry, doubts were
raised by Koenig et al. (154: 1369-1375) about the appropriate use of
antidepressant medication by non-psychiatrists in general medical settings.
They found a familiar pattern of undertreatment (only 40.5% patients received
antidepressants, often at inadequate doses) in conjunction with a strong
preference for using tricyclic antidepressants (amitriptyline was prescribed
in 45.2% of those receiving antidepressants). Most alarming was the high use
of benzodiazepines as the primary treatment intervention (25.5%). These
findings add to evidence highlighting the overprescription of benzodiazepines
and the underprescription of antidepressants in the elderly and emphasise the
continuing need to influence practice in non-psychiatric settings.
October saw a further contribution to the debate surrounding subjective
memory complaints (Schmand et al., British Journal of Psychiatry 171:
373-376). This large study of nondemented elderly subjects (n=2114) found
memory complaints were not completely explained by depression and actually
reflected realistic concerns. Subjective complaints may, after all, herald
cognitive decline, at least in some patients.
A standardized on-road test may be the only appropriate means of
determining driving competence in people with AD, according to Fox et al.
(Journal of the American Geriatrics Society 45: 949-953). The on-road driving
performance of subjects was not predicted by a physician, neuropsychologist,
or neuropsychology assessment. In addition, over a third of AD subjects passed
the on-road test, supporting the view that a decision to stop driving requires
more than a diagnosis.
Since the detection of the Huntington disease (HD) gene in 1993,
attention has focused on understanding how trinucleotide repeats influence the
disease process. Jason et al. (Archives of Neurology 54: 1081-1088) reported a
negative correlation between cognitive decline and the number of repeats in
patients both with and at risk of HD. These results are consistent with other
studies and suggest higher numbers of trinucleotide repeats are associated
with a more accelerated decline. · Might having children late in one's life be
a marker of longevity? Reporting in Nature (389: 133), 78 female centenarians
were compared with a comparable birth cohort of 54 women who died aged 73. The
centenarians were four times more likely to have had children in their 40s. ·
Results from Australia (Brodaty et al., Psychological Medicine 27:1205-1213)
expand on previous studies showing clinical differences in depression between
young and old. Rates of psychosis and psychomotor change increased with age,
though there were no differences between elderly subjects with early or late
onset depression. · All old age psychiatrists may identify with the findings
of a survey from the UK assessing the causes of "stress" (Benbow et al.,
International Journal of Geriatric Psychiatry 12:879-882). The most frequent
category of stress was related to overwork (56%), followed by issues relating
to management (43%), resources (38%), personal problems (33%), and lack of
time (30%). The good news was that the authors felt many of the causes of
stress were potentially amenable to modification. · A potential mediator in
the amyloid pathogenesis of AD is reported by Yan et al. (Nature 389:
689-695). Using cell cultures, they identified an intracellular protein, ERAB
(endoplasmic-reticulum-associated binding protein) which is overexpressed in
AD. This protein appears to interact with amyloid-b (Ab) to form an ERAB-Ab
complex, causing translocation of ERAB to the plasma membrane. The neurotoxic
effects of Ab were prevented by inhibition of ERAB and increased by
overexpression of ERAB. · The "autocannibalism hypothesis" of AD has been
investigated using brain proton magnetic resonance (1H-MRS) to measure changes
in brain chemistry after treatment with a muscarinic selective cholinergic
agonist, xanomeline (Satlin et al., American Journal of Psychiatry 154:
1459-1461). As predicted by the hypothesis, treated subjects had a decrease in
MRS choline resonance (postulated by the authors to reflect decreased
degridation of choline-containing compounds such as membranes). However, the
clinical relevance of this finding needs to be explored further using a
larger, controlled sample.
Uncertainties regarding the validity of the "DNA damage" theory of aging
were raised by a study from Dollé et al. (Nature Genetics 17: 431-434). Using
a transgenic mouse model, they were able to examine the rate of spontaneous
somatic mutations in liver and brain tissue. Age-related increases were
observed only in liver tissue, perhaps suggesting organ-specific differences
in the aging process. As the authors discuss, it remains to be shown whether
up-regulation of DNA repair would retard mutation accumulation and increase
longevity.
Evidence linking the new variant of Creutzfeldt-Jakob disease (nvCJD)
with bovine spongiform encephalopathy (BSE) has been strengthened by the
findings of two recent reports in Nature. Hill et al. (389: 448-450) found the
nvCJD and BSE agents were biochemically indistinguishable (and different from
other forms of CJD). Bruce et al. (389: 498-501) injected mice with infectious
brain samples and found those from nvCJD and BSE sources produced identical
histological and symptomatic changes, again different from other forms of CJD.
· Yet another common age-related disorder has been linked to a specific gene.
Reporting in Science, Dean et al. (277: 1805) suggest the gene ABCR
(ATP-binding cassette transporter-retina) could account for 16% of age-related
cases of macular degeneration. Questions regarding the underlying pathogenesis
remain, but it may represent the first "chink in the armour." John O'Brien,
DM, MRCPsych, was appointed senior lecturer in old age psychiatry at the
University of Newcastle upon Tyne in 1995. He works clinically as a consultant
in old age psychiatry for the Newcastle City Health NHS Trust. Born in 1962,
he undertook preclinical studies at Robinson College, Cambridge University,
before moving to Green College, Oxford University, for clinical studies. Dr.
O'Brien trained in psychiatry at the Maudsley Hospital and Institute of
Psychiatry in London, where he was heavily influenced by many key figures at
the Institute, particularly Professor Raymond Levy, who encouraged his
academic interests and involvement in old age psychiatry. He moved next to
Cambridge and then to Melbourne, Australia, where he spent two years as
lecturer in old age psychiatry at the University of Melbourne under the
auspices of associate professors David Ames and Edmond Chiu. His research work
in Melbourne formed the basis for a DM thesis and directly led to his current
areas of research activity and interest, which include the application of
neuroimaging, particularly MRI and SPET, to psychiatric disorders in late life
and the neurobiology of depression. He is also involved in undergraduate and
postgraduate education, and has recently become a member of the Medical and
Scientific Advisory Panel of Alzheimer's Disease International. Together with
Professor Ian McKeith, he will host an IPA meeting in Newcastle in the year
2000. Bob Barber, MRCPsych, MSc, moved to Newcastle upon Tyne, UK, in 1996,
following his appointment as a lecturer in old age psychiatry at the
University of Newcastle upon Tyne. Born in 1963, he was an undergraduate at
Nottingham University where he studied under Professor Tom Arie and Dr. Jane
Byrne. His postgraduate psychiatry training in general adult psychiatry and
old age psychiatry has been undertaken in Manchester and Newcastle upon Tyne
as well as one year in Adelaide, Australia. His work in internationally
recognised departments of old age psychiatry has stimulated his current
research interests in presenile dementias and the application of neuroimaging
to the study of dementias. As a member of the University, he is actively
involved in undergraduate and postgraduate education.
Drs. John O'Brien and Bob Barber are the IPA Bulletin's
research editors. They welcome comments via (fax) +44 191 219 5040 or (e-mail)J.T.O'Brien@ncl.ac.uk
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.
