IPA Bulletin
Recent Advances - Volume 17, Number 2
John O'Brien and Bob Barber
We have previously reported that a mutation in the a 2 -macroglobulin
gene (A2M) on chromosome 12 is linked to late-onset Alzheimer’s
disease (AD) (Tanzi et al. Nature Genetics 1998;19:321-2), a finding that
was replicated in a recent study from Finland (Annals of Neurology
1999;46:382-390). The gene has been implicated in the clearance and
degradation of ß-amyloid, and given that cerebral amyloid angiopathy
(CAA) is frequently found in AD, Yamada et al. (Stroke 1999;30:2277-
2279) investigated the association between the A2M and CAA. They
found A2M deletion allele was not linked to CAA formation in both
AD and non-AD subjects. In a separate study, Schwab et al. (Dementia
1999;10:469-472) failed to find any association between another candidate
gene, on this occasion a 1 -antichymotrypsin, and AD.
There has been a rapid expansion in recent years in the availability of
memory clinics, but do such clinics work? Lodiudice et al. (International
Journal of Geriatric Psychiatry 1999; 14: 626-632) reported a randomized,
controlled trial of 50 community-dwelling subjects with mild to mod-erate
dementia and their carers who were randomized to attend a
memory clinic or act as a control group. Those carers attending the
memory clinic were found to have significant improvement in psy-chosocial,
health-related quality of life, including improvements in
social interaction and 'alertness' behavior. This improvement in
social interaction was maintained at 12 months. Perhaps surprising-ly,
there were no differences in carer psychological morbidity as
assessed by the General Health Questionnaire, carer burden, or carer
knowledge of dementia. The authors suggested their results demon-strate
that memory clinics do indeed improve some aspects of quality
of life for carers.
Yet another indication that changes in brain function changes can be
detected many years before the onset of AD is provided by Smith et al.
(Neurology 1999; 53: 1391-1396) who, using functional MRI, compared
cortical activation during neuropsychological tasks in subjects with-out
and with risk factors for AD (as judged by family history and pos-session
of Apolipoprotein E-4 allele). High-risk subjects showed
areas of significantly reduced activation in frontotemporal regions
bilaterally during both tasks. Importantly, this occurred despite iden-tical
accuracy of performance. The authors suggested the importance
of their finding may lie in the identification of subjects at risk for
dementia who should be targeted with potential disease-modifying
treatments.
Several studies have shown the poor outcome of depression in the
elderly without treatment. Cole et al. (American Journal of Psychiatry
1999; 156: 1182-1189) reported a systematic review and meta-analysis
of 12 population-based studies of the elderly investigating the out-come
of depression. Although the authors found that all the studies
had some methodological limitations, a meta-analysis of outcome at
24 months found that 33% of subjects who had been depressed at
baseline were well, 33% were still depressed and 21% had died. Poor
outcome was associated with physical illness, disability, the presence
of cognitive impairment and more severe depression. The authors
concluded that their findings add support to efforts to develop detec-tion
and treatment programs for depression in the general population.
Three studies report on prodromal changes which can be demonstrat-ed
in subjects who later develop AD. Louis et al. (International Journal of
Geriatric Psychiatry 1999; 14: 941-945) found that elderly medical inpatients without dementia at baseline, who scored more than 3.31 on
the short form of the informant questionnaire on cognitive decline in
the elderly (IQCODE), were more likely to develop dementia over a
two-year follow-up period. Almost half of those scoring above the
cut-off on the IQCODE developed dementia, compared to less than
4% of controls. Touchon and Ritchie (International Journal of Geriatric
Psychiatry 1999; 14: 556-563) reported a general population cohort of
397 normal elderly subjects examined over a three-year period.
Twenty-two who developed AD were compared retrospectively with
150 subjects who had remained free of psychiatric disorder.
Significant differences between the two groups on a wide range of
cognitive tests were found up to two years before diagnosis.
Differences were greater in those with low levels of education, sug-gesting
that high education levels may prolong competence, particu-larly
for verbal tasks. Finally, Nielsen et al. (International Journal of
Geriatric Psychiatry 1999; 14: 957-963), again studying a population
sample of 2,452 subjects at baseline and two years later, found that
the 102 subjects who developed AD had significantly lower CAMCOG
scores on all subscales than those who remained non-demented.
Differences were particularly pronounced for recent and remote mem-ory,
verbal fluency, and attention. Appropriate cut-offs were able to
result in sensitivity of 70% and specificity of 80% for the selection of
those with prodromal dementia, though given the large number of
subjects who remained non-demented, in terms of positive predictive
value the CAMCOG cut-off performed at less than 20%.
Although there is a large literature assessing the impact of neuropsy-chiatric
symptoms on carer distress, there has been relatively little
attention paid to the impact of these symptoms in professional,
rather than unpaid, caregivers. Wood et al. (Aging and Mental Health
1999; 3: 241-245) investigated the effects of neuropsychiatric symp-toms
(as assessed by the Neuropsychiatric Inventory) and levels of
distress in two types of nurses, licensed vocational nurses and certi-fied
nurse aids. The most distressing behaviors for both staff groups
were agitation and apathy. However, while levels of distress for
licensed vocational nurses approached those reported by family
members in previously published research, certified nurse aides
reported very little overall distress. The authors concluded that dis-tress
in professional care givers is a significant, and often neglected,
problem in long-term care settings.
Seasonal trends have been shown to exist for a number of psychiatric
disorders, but is there any evidence that the weather influences
admissions for organic disorders such as dementia? Not according
to Salib and Sharpe (International Journal of Geriatric Psychiatry 1999; 14:
925-935) who investigated daily hospital admissions for dementia in
one area of the UK in relation to meteorological data. There was no
evidence of any statistically significant association between weather
parameters and dementia admissions.
The importance of suicidal ideation is well known by all Old Age Psychiatrists but a recent study sought to determine which elderly
subjects with depression were at risk with regard to thoughts of self-harm.
Alexopolous et al. (Archives of General Psychiatry 1999 56: 1048-
1053) studied 354 patients over the age of 60 with depression who
were assessed every six months for a two-year period. Suicidal
ideation during depression was associated with previous suicide
attempts, increased severity of depression, and poor social support.
The most important predictor of continued suicidal ideation at
follow-up was severity of depression at baseline. These findings
reinforce the need to take suicidal ideation seriously in elderly
depressed patients and the requirement for careful clinical follow-up
of those with the greatest severity of illness.
The well documented association between depression and
increased mortality in the elderly is given further weight by
Penninx et al. (Archives of General Psychiatry 1999; 56: 889-895) who
studied a community dwelling population of 3,056 subjects in the
Netherlands followed up for up to four years. Major depression
was associated with a 1.8-fold increase in mortality after adjust-ment
for associated demographic and health status. Minor
depression was also associated with a similar increase in deaths,
though this effect was only significant for males. By looking at
potential confounders, the authors felt that health behaviors such
as smoking explained only a small part of the excess mortality
associated with depression. This study emphasizes once again
the importance of elucidating mechanisms which underlie this
association.
How much can we rely on patients recalling a past episode of
depression when we take a psychiatric history? This important
topic is the subject of a paper by Andrews et al. (Psychological
Medicine 1999; 29: 787-791) who followed up 45 patients who had
definitely suffered from a major depressive episode (for which
they were hospitalized) at baseline. Only 70% could recall being
depressed and only 50% recalled sufficient detail to satisfy diag-nostic
criteria when interviewed 25 years later. The authors sug-gested
that as depressive episodes, particularly those severe
enough to warrant hospital admission, are likely to be recorded
better than other psychiatric disorders, we should remain cau-tious
about lifetime prevalence rates for psychiatric disorder
reported in retrospective epidemiological surveys.
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.
