IPA Bulletin
Recent Advances - Volume 15, Number 4
John O'Brien and Bob Barber
The introduction of antidementia agents has stimulated debate about
their cost effectiveness. Knapp et al. (International Journal of
Geriatric Psychiatry 1998; 13:531-543) argue that although long term
outcome studies are needed, antidementia treatments have potential to offer
cost savings for many patients. Stuart et al. (International Journal of
Geriatric Psychiatry 1998; 13:445-453) present a five year Markov model
for patients aged over 75, and calculate overall costs were higher for
placebo than donepezil-treated patients. Although a controversial area, such
findings mirror similar studies of newer antidepressants and suggest that
drugs which appear expensive in the short term may ultimately save money.
In a longitudinal study of non-cognitive symptoms in dementia McShane,
et al (Psychological Medicine 1998; 28:1119-1127) assessed 86
community-dwelling subjects with dementia every four months for up to four
years. Two distinct symptom patterns emerged: initial sad appearance
predicted later development of physical aggression, while initial
persecutory ideation predicted motor hyperactivity. Although underlying
mechanisms are not known, it is tempting to speculate that specific
neurochemical mechanisms underlie these symptom profiles.
Memory clinics are becoming popular but there are scant data on their
effectiveness. A pilot study (Moniz-Cook et al., Aging and Mental
Health 1998; 2:199-211) describes a comparison of standard care
following memory clinic consultation (feedback and leaflets) to a 10-session
educational intervention program. At 18-month follow-up, improvements were
found in memory scores of the experimental group, whose carers were less
stressed than controls. The study provides further support that early
diagnosis, combined with early intervention, can have lasting benefits on
patients with dementia and their carers.
The importance of parental loss in early life as a risk factor for
depression remains controversial. Kivela et al. (International Journal of
Geriatric Psychiatry 1998; 13:527-530) report a Finnish-based
longitudinal study of 679 people interviewed at baseline and five years
later. Loss of mother before the age of 20 in men and loss of father before
the age of 20 in women independently predicted the occurrence of depression
in late life. The authors speculate that early loss makes individuals
vulnerable to future traumatic life events and stressful life situations
Geula et al. (Nature Medicine 1998; 7:827-831, 1998) have shown
that injections of ß amyloid into the brains of aged (but not young) monkeys
result in profound neuronal loss, tau phosphorylation and microglial
proliferation. This finding is important as in previous animal models of
Alzheimer's disease (AD), raised amyloid levels had not proved neurotoxic.
The authors speculate that longevity may explain the unique susceptibility
of humans to AD by rendering the brain vulnerable to ß amyloid
neurotoxicity.
Treatment resistance was found to occur in 18% of elderly depressed
subjects undergoing treatment with nortriptyline, interpersonal
psychotherapy, and augmentation therapy in standardized fashion (Little et
al., American Journal of Psychiatry 1998; 155:1035-1038). That such
treatment resistance may be due to neurobiological factors is supported by a
study by Simpson et al. (Psychological Medicine 1998; 28:1015-1026)
who assessed 75 consecutive depressed patients presenting to an old age
psychiatry service. A poor response to antidepressant monotherapy was
predicted by impairments on psychometric tests sensitive to frontal lobe
damage, extrapyramidal signs or white matter lesions on MRI in basal ganglia
and the pontine reticular formation. Whether such changes are due to
vascular disease is not clear (Hickie & Scott, Psychological
Medicine 1998; 28:1007-1013), though a further link between depression
and vascular disease is demonstrated by Ford et al. (Archives of Internal
Medicine 1998; 158:1422-1426). They report results from 1190 male
medical students enrolled in the 1950s and followed up at 40 years. Men who
reported clinical depression were at significantly greater risk for
subsequent coronary artery disease (relative risk 2.1), even for myocardial
infarctions that occurred 10 years after the onset of the first depressive
episode.
To ApoE, APP, PS1 and PS2 can now be added a2M.
A recent study by Tanzi and colleagues (Nature Genetics
1998;19:321-2) found that a mutation in the a2-macroglobulin (A2M) gene on
chromosome 12 was linked to late-onset AD. This gene normally mediates the
clearance and degradation of ß amyloid, raising the possibility that a
defect could lead to an accumulation of amyloid and subsequent plaque
formation. The risk attributed to this mutation appeared to be dose related
and independent of ApoE 4 status. Some researchers have suggested ApoE
determines "when" and A2M "whether" AD develops.
Predicting how individuals suffering from dementia adapt to long-term
care can be difficult. A study by Brandt et al. ((International Journal
of Geriatric Psychiatry 1998;13:509-15) examined the relationship
between premorbid personality and social adaptation in 28 nursing home
residents. Personality variables had little effect on adaptation.
Two separate studies (Kilander et al. Stroke 1998;29:1816-20;
O'Connell et al., (Journal of Neurology, Neurosurgery and Psychiatry
1998; 65:386-9) have found a link between atrial fibrillation and poor
cognitive function. This association may be mediated through silent cerebral
infarctions, and raises the hope that antithrombotic treatments may prevent
cognitive decline and dementia.
Beecroft et al. ((International Journal of Geriatric Psychiatry
(1998; 13:638-41) describe an unusual case of pica in a 75-year-old lady
with a long standing schizophrenia and CT evidence of temporal and frontal
atrophy. By the time the patient underwent an emergency laparotomy, she had
accumulated £175.32 (approximately $280US) of loose change in her stomach!
After a disappointing response to neuroleptics, a regime of
cognitive-behavioural therapy proved to be modestly effective.
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.
