IPA Bulletin
Recent Advances - Volume 15, Number 3
John O'Brien and Bob Barber
A recent publication that will be of interest to all members is
"Diagnosis of Alzheimer's Disease," a supplement to International
Psychogeriatrics (Volume 9, Supplement 1), edited by Barry Reisberg and
Alistair Burns. This is the product of a special meeting in Geneva in
November 1996 co-sponsored by IPA, Alzheimer's Disease International, the
European Federation of Neurological Societies, the World Health Organisation
and the World Psychiatric Association. The volume contains over 40 papers
covering all aspects of diagnosis and assessment, including the use of
assessment scales, peripheral markers, neuroimaging and neuropathological
assessment.
In a population-based study in Massachusetts, Paris et al. (Lancet 1998; 351:1560) compared survival of siblings of centenarians and those
with siblings of similar birth cohort who died in their early 70s. They
found that siblings of centenarians had a four times greater chance of
surviving to age 90 than siblings of those who died earlier. This is yet
another study suggesting a genetic influence on longevity, though the
authors point out shared environmental risk factors also may be important.
The differentiation between depression and dementia remains a sometimes
difficult clinical decision. Yousef et al. (International Journal of
Geriatric Psychiatry 1998; 13:389-399) suggest a new scale of 18
questions, based on 44 features previously described in the literature as
possibly being helpful, that differentiated between cases of dementia (98%
accuracy) and cases of depression (95% accuracy) in their study. The
accuracy appears impressive, though some of the definitions of
pseudodementia used (for example, a score of 8 on the Montgomery Asberg
Depression Rating Scale and a subjective complaint of poor memory) might be
questioned by other researchers in the area.
The notion that recently bereaved elderly subjects are at increased risk
of mortality receives further support from a twin study by Lichtenstein et
al. (Psychological Medicine 1998; 28:635-643) who examined 1993 pairs
of twins discordant for marital status from the Swedish Twin Registry. Using
the still-married co-twin as a control, they found that bereavement was a
risk factor for mortality in both men and women, with risk highest for those
under 70 years and for those most recently (within 6 months) bereaved.
However, data on cause of death were not given.
The relationship between cigarette smoking and risk of Alzheimer's
disease (AD) remains controversial. Some previous studies have suggested
that smoking exerts a protective effect, but a recent report using the
population-based Rotterdam Study of nearly 8,000 subjects aged over 65
suggests that smoking may increase the risk (Ott et al., Lancet 1998; 351:1840-1843). Some 6,870 participants who were
non-demented at baseline and who had an adequate smoking history were
followed for two years. Smokers had an increased risk of both dementia
(relative risk 2.2) and AD (relative risk 2.3), but smoking was only a risk
factor in those without the ApoE Î 4 allele
(relative risk 4.6) and not in those with the ApoE Î 4 allele (relative risk 0.6).
The clinical use of carbamazepine for the treatment of behavioural
disturbance in dementia is given further support by a 6 week, randomised,
placebo-controlled trial of 51 nursing home residents with inappropriate
verbal, vocal, or motor activities (Tariot et al., American Journal of
Psychiatry 1998; 155:54-61). Individual dosing was used, (mean
300mg/day). BPRS scores decreased 7.7 points in the carbamazepine group and
0.9 in a placebo group, while clinical global impression showed improvement
in 77% of those taking carbamazepine and 21% of those taking placebo. Staff
reported that less intervention time was needed in those taking
carbamazepine. The drug was generally well tolerated with no adverse effects
on cognition.
Two papers describe the efficacy of Metrifonate in the treatment of AD.
The first (Cummings et al., Neurology 1998; 50:1214-1221) describes a
30-week, double-blind, randomised dose finding study of 480 patients. After
12 weeks treatment, a score on the ADAS-Cog improved by just under 3 points
with a one-third of a point increase on the clinician's interview-based
impression of change (CIBIC-PLUS). Side effects, as with other
cholinesterase inhibitors, were predominantly gastrointestinal, and no
hepatic toxicity was observed. A second paper (Morris et al., Neurology 1998; 50:1222-1223) describes 408 patients treated for 26 weeks in
double-blind fashion with 30-60mg of Metrifonate. After 26 weeks of
Metrifonate treatment, again an improvement on the ADAS-Cog of just under 3
points was observed with a similar improvement on the CIBIC-PLUS. There also
was a significant improvement in non-cognitive symptoms as assessed by the
Neuropsychiatric Inventory (NPI). The greatest effect was a reduction in
hallucinations in the treatment group. These data add to others suggesting
that cholinesterase inhibitors may be useful in treating non-cognitive as
well as cognitive features of AD.
Another study suggesting that elderly patients with depressive symptoms
have a poor outcome has been reported by Penninx et al. (Journal of the
American Medical Association 1998; 279:1720-1726). In a community study
in Iowa, 1,286 people over the age of 70 were assessed at baseline and 4
years later. Depressive symptoms at baseline predicted greater decline in
physical performance over the follow-up period, even in those who had no
disability at baseline.
Koenig et al. (American Journal of Psychiatry 1998; 155:536-552)
point out that despite the obvious importance of religious attitudes, few
studies have investigated their effect on outcome. In 111 depressed patients
admitted to inpatient medical services, religious beliefs were investigated
as predictors of time to remission of depressive symptoms. What the authors
term "intrinsic religiosity" was significantly related to time to remission,
independent of demographic, physical health, psychosocial, and treatment
factors. However, overt religious activity (e.g. church attendance and
private religious activities) were not related to outcome. The authors feel
theirs is the first report in which religiosity has been examined as a
predictor of outcome of depressive disorder.
AIDS may be relatively uncommon in people over 60 years (accounting for
just 3% of cases), but Chen et al. (Journal of the American Geriatrics
Society 1998; 46:153-156) found sexual transmission of AIDS had replaced
transmission by contaminated blood products as the leading cause in older
people. Drug misuse was the third most common cause. Examining the Maryland
AIDS Registry from 1981 to 1994, they also found older patients (>60
years) had a considerably shorter survival than younger patients (median
life span of 9 months compared with 22 months). An older person presenting
with Pneumocystis carinii pneumonia, wasting syndrome, candidiasis or
encephalopathy should raise suspicion of infection. In view of the changing
pattern of transmission, the authors highlight the need for appropriate
preventive and educational measures.
The impact of aging on the human brain appears to be greater in men than
women, according to the findings of an imaging study by Coffey et al.
(Archives of Neurology 1998; 55:169-179). They examined 330 healthy
elderly volunteers between the ages of 66-96 using quantitative MRI and
found brain morphology was, at least in certain areas, sensitive to the
effects of both age and sex, with men showing more age-specific changes.
Whether these findings should be a source of concern for men is not known,
but the authors suggest that further clarification of the functional
significance of these differences is required.
In the first edition of this column, we reported a link between the
syndrome of "Frontotemporal dementia and Parkinsonism" to chromosome 17
(FTDP-17). Since then, Schellenberg et al. (Annals of Neurology 1998;
43:815-25) have identified a point mutation of valine to methionine in the
tau gene located on chromosome 17, and soon-to-be-published work reported in
Science (280, 5 June 1998) suggests other investigators also have
linked tau mutations to inherited forms of dementia similar to FTDP-17. The
underlying molecular pathogenesis remains to be discovered, but there is
excitement that these findings will improve our understanding of tau
pathology in not only FTDP-17 but also in related degenerative disorders
with tangle formation.
It has been suggested that levodopa therapy may be neurotoxic. Using a
rat model of Parkinson's disease, Murer and colleagues (Annals of
Neurology 1998; 43:561-575) examined the effects of 6-month oral
levodopa treatment on a range of dopaminergic markers. In contrast to
findings from in vitro studies, they found levodopa was not toxic and
may even promote recovery of striatal innervation. Whether or not these
effects are evident in humans will be the subject of an NIH-funded,
prospective controlled clinical trial in newly diagnosed patients with the
disorder.
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.
