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Effect of gonadectomy on subsequent development of age-related cognitive impairment in dogs

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To determine whether gonadectomy predisposes dogs to development of age-related behavioral changes linked to cognitive impairment. Cohort study. 29 sexually intact male dogs, 63 spayed female dogs, and 47 castrated male dogs 11 to 14 years old. Information on possible impairments in 4 behavioral categories linked to cognitive impairment (orientation in the home and yard, social interactions, house training, and sleep-wake cycle) was obtained from owners of the dogs by use of a structured telephone interview format. A second interview was performed 12 to 18 months after the initial interview, and differences in responses were evaluated. Sexually intact male dogs were significantly less likely than neutered dogs to progress from mild impairment (i.e., impairment in 1 category) to severe impairment (i.e., impairment in > or = 2 categories) during the time between the first and second interviews. This difference was not attributable to differences in ages of the dogs, duration of follow-up, or the owners' perceptions of the dogs' overall health. Results suggest that the presence of circulating testosterone in aging sexually intact male dogs may slow the progression of cognitive impairment, at least among dogs that already have signs of mild impairment. Estrogens would be expected to have a similar protective role in sexually intact female dogs; unfortunately, too few sexually intact female dogs were available for inclusion in the study to test this hypothesis. There may be a need to evaluate possible methods for counteracting the effects of loss of sex hormones in gonadectomized dogs.
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JAVMA, Vol 219, No. 1, July 1, 2001 Scientific Reports: Original Study 51
SMALL ANIMALS/
EXOTICS
I
mproved veterinary care and nutrition and safer
home environments are allowing dogs to live well
into their senior years. Thus, there is increased interest
in the behavior and welfare of aging dogs. In addition
to age-related changes in the musculoskeletal, cardio-
vascular, and endocrine systems, caregivers of dogs and
their veterinarians have recognized a number of behav-
ioral changes that occur in senior dogs that appear to
reflect disturbances of memory and learning.
1
Because
memory and learning are integral components of ani-
mal cognition,
2,3
the terms cognitive impairment and
cognitive dysfunction have been introduced to refer to
these behavioral changes in senior dogs.
4-6
The term
canine cognitive dysfunction syndrome was recently
introduced in association with US Food and Drug
Administration approval of selegiline
a
for treatment of
this syndrome.
7
Behavioral changes in senior dogs with cognitive
impairment can be classified into 4 general cate-
gories
1,8
: disorientation in the home or yard, changes in
social interactions with human family members, loss of
house training, and changes in the sleep-wake cycle.
The first 3 categories comprise behavioral signs that
clearly reflect loss of memory and learning. Changes in
the sleep-wake cycle would appear to reflect disrup-
tions in the circadian rhythm; however, adaptation of
the crepuscular activity pattern of wild canids (active
at dusk and dawn) to the diurnal pattern of human
family members represents a type of learning, and dis-
ruption of the sleep-wake cycle is common in humans
with Alzheimer’s disease.
9,10
In a previous study,
1
the prevalence of behavioral
impairments in senior dogs was significantly associat-
ed with age. Twenty-eight percent of dogs 11 to 12
years old had impairments in 1 or more categories, and
10% had impairments in 2 or more. By contrast, 68%
of dogs 15 to 16 years old had impairments in 1 or
more categories, and 35% had impairments in 2 or
more. A related study
8
of dogs 11 to 14 years old found
that over a period of 6 to 18 months, almost all dogs
became more impaired or stayed the same. Only 2 of
37 dogs that were initially found to have impairments
in a particular category were later found not to have
impairments in that category. In addition, 13 of 27
(48%) dogs initially found to have impairments in only
1 category were later found to have impairments in 2
or more categories, whereas only 8 of 73 (11%) dogs
that did not initially have any impairments were later
found to have impairments in 2 or more categories.
Despite the obvious species-specific differences,
behavioral changes in senior dogs appear similar to
those in humans with dementia, particularly those
with Alzheimer’s disease, in which decreased recogni-
tion of family members, disorientation in the home or
neighborhood, disturbances of the sleep-wake cycle,
and, eventually, inappropriate urination or defecation
are common.
9,10
As in dogs with cognitive impairment,
changes in humans with Alzheimer’s disease are pro-
gressive.
11-14
The primary neuropathologic changes in humans
with Alzheimer’s disease are accumulation of β-amy-
Effect of gonadectomy on subsequent
development of age-related cognitive
impairment in dogs
Benjamin L. Hart, DVM, PhD, DACVB
Objective—To determine whether gonadectomy pre-
disposes dogs to development of age-related behav-
ioral changes linked to cognitive impairment.
Design—Cohort study.
Animals—29 sexually intact male dogs, 63 spayed
female dogs, and 47 castrated male dogs 11 to 14
years old.
Procedure—Information on possible impairments in
4 behavioral categories linked to cognitive impairment
(orientation in the home and yard, social interactions,
house training, and sleep-wake cycle) was obtained
from owners of the dogs by use of a structured tele-
phone interview format. A second interview was per-
formed 12 to 18 months after the initial interview, and
differences in responses were evaluated.
Results—Sexually intact male dogs were significant-
ly less likely than neutered dogs to progress from
mild impairment (ie, impairment in 1 category) to
severe impairment (ie, impairment in 2 categories)
during the time between the first and second inter-
views. This difference was not attributable to differ-
ences in ages of the dogs, duration of follow-up, or
the owners’ perceptions of the dogs’ overall health.
Conclusions and Clinical Relevance—Results sug-
gest that the presence of circulating testosterone in
aging sexually intact male dogs may slow the pro-
gression of cognitive impairment, at least among
dogs that already have signs of mild impairment.
Estrogens would be expected to have a similar pro-
tective role in sexually intact female dogs; unfortu-
nately, too few sexually intact female dogs were avail-
able for inclusion in the study to test this hypothesis.
There may be a need to evaluate possible methods
for counteracting the effects of loss of sex hormones
in gonadectomized dogs. (
J Am Vet Med Assoc
2001;
219:51–56)
From the Behavior Service, Veterinary Medical Teaching Hospital,
School of Veterinary Medicine, University of California, Davis, CA
95616.
Supported in part by the UC Davis Center for Companion Animal
Health.
The author thanks Drs. Kelly Cliff, Melissa Bain, and Jacqueline
Neilson for technical assistance and Dr. Neil Willits for assistance
with statistical analyses.
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52 Scientific Reports: Original Study JAVMA, Vol 219, No. 1, July 1, 2001
SMALL ANIMALS/
EXOTICS
loid peptide in the frontal cortex and hippocampus and
formation of β-amyloid plaques associated with neu-
ronal death.
9,10
The amount of β-amyloid correlates
with the severity of dementia in patients with
Alzheimer’s disease.
15
Aged dogs also accumulate
β-amyloid deposits in the hippocampus and frontal
cortex,
16-19
and these deposits are similar to the primi-
tive or early-stage plaques seen in the brains of humans
with Alzheimer’s disease.
20,21
Advanced senile plaques
have not been found in dogs, but laboratory research
on aging Beagles has shown that the degree of β-amy-
loid deposition corresponds to the degree of impair-
ment in learning complex tasks.
22,23
Interestingly,
selegiline not only improves behavioral signs in dogs
with cognitive impairment
7
but also slows the progres-
sion of degenerative changes in human patients with
Alzheimer’s disease.
24
Various studies
25-28
have found that post-
menopausal women receiving estrogen-replacement
therapy had a lower risk of developing Alzheimer’s dis-
ease, even when variables such as education, ethnicity,
socioeconomic status, age at menarche, age at
menopause, number of children, and ApoE
4
genotype
were taken into account. In addition, estrogen treat-
ment of postmenopausal women with Alzheimer’s dis-
ease enhanced cognition,
29
although whether estrogen
enhances cognitive function in older women without
dementia is less certain.
30,31
Clinical studies on the role of testosterone in cog-
nitive function in men are more limited, but recent
work suggests that among older men, those with high-
er testosterone concentrations and lower estradiol con-
centrations performed better than those with lower
testosterone concentrations on tests of cognitive func-
tion,
32
and testosterone can enhance verbal fluency in
hypogonadal men.
33
There is research that suggests estrogen potenti-
ates memory and learning in rodents, and ovariectomy
results in a decline in learning ability and memory.
34-37
Estradiol appears to enhance memory by interacting
with cholinergic systems involved in memory modula-
tion.
38,39
Estrogen maintains the neural circuitry and
neural transmitter systems in the hippocampus and
frontal cortex,
40-42
and both estrogen
43,44
and testos-
terone
45
reduce accumulation of the β-amyloid materi-
al that comprises the neural plaques associated with
cognitive impairment in humans and dogs.
Testosterone has also been found to prevent hyper-
phosphorylation of the neuroprotective protein tau,
which is abnormally hyperphosphorylated in human
patients with Alzheimer’s disease.
46
Cerebral glucose
utilization and cerebral blood flow are enhanced by
estrogen,
47,48
and estrogen serves to combat oxidative
stress.
49-51
Taken together, this research suggests that the sex
hormones may play a role in preventing development
of age-related cognitive impairment in dogs. The pur-
pose of the study reported here, therefore, was to deter-
mine whether gonadectomy predisposes dogs to devel-
opment of age-related behavioral changes linked to
cognitive impairment. Because in a previous study,
1
only 10% of castrated male and spayed female dogs
were found to have severe cognitive impairment
(ie, impairment in 2 behavioral categories), it seemed
unlikely that a cross-sectional study would be able to
detect significant differences in prevalence of severe
impairment between neutered and sexually intact dogs
unless an extremely large number of dogs were
enrolled in the study. Therefore, the present study was
structured to determine whether percentage of senior
dogs that progressed from mild cognitive impairment
(ie, impairment in only 1 behavioral category) to
severe impairment over a period of 6 to 18 months was
significantly different between sexually intact and
neutered dogs.
Materials and Methods
The study was conducted in parallel with a longitudinal
study of the progression of age-related behavioral impair-
ments in dogs.
8
Briefly, information on possible behavioral
changes linked to cognitive impairment was obtained from
owners of dogs 11 to 14 years old by use of a structured tele-
phone interview format. A second interview was performed
12 to 18 months after the initial interview, and differences in
responses were evaluated. Because of the advanced age of the
dogs included in the study, some dogs were euthanatized or
died of disease before the second interview could be per-
formed. However, the second interview was still performed
and the data were used if the dog had lived at least 6 months
after the first interview.
Selection of dogs—Records of the University of
California, Davis, Veterinary Medical Teaching Hospital
were searched to identify dogs 11 to 14 years old. Hospital
records for these dogs were screened, and dogs with med-
ical problems that may induce signs similar to cognitive
impairment were eliminated. Owners of a random sample
of the remaining spayed female and male castrated dogs and
of all remaining sexually intact dogs were contacted by tele-
phone to determine whether dogs were still alive, whether
the dogs had any medical problems not apparent from the
hospital records that may induce signs similar to cognitive
impairment, and whether the owners were willing to par-
ticipate in the study. Owners of all sexually intact male dogs
that met the criteria for inclusion were invited to partici-
pate, because there were so few records of sexually intact
male dogs. Dogs were considered to be sexually intact if
they were intact at the time of the first interview or if they
had been castrated 1 year previously. Almost all female
dogs were spayed, so sexually intact female dogs were not
included in the study.
Interview format and questions—During the initial
telephone contact with owners who agreed to participate in
the study, an appointment for the first structured telephone
interview was made. These owners were sent an information
sheet about possible age-related behavioral changes prior to
the first interview. Owners were not told they would be called
for a second interview. Because clients were sent information
about possible behavioral changes prior to the first interview,
and there was a 12- to 18-month delay before the second
interview, bias associated with sensitization of owners to age-
related changes during the second interview should have
been minimal. The first and second interviews were con-
ducted by different veterinary behaviorists, but the same
structured format was used by both.
Dogs were considered to have an impairment in any par-
ticular behavioral category if they were exhibiting 2 specif-
ic signs related to an impairment in that category and had not
been exhibiting those signs earlier in their lives (ie, at 5 to 8
years of age). Dogs were considered to have an impairment in
orientation in the home or yard if they had 2 of the follow-
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JAVMA, Vol 219, No. 1, July 1, 2001 Scientific Reports: Original Study 53
SMALL ANIMALS/
EXOTICS
ing or similar signs: staring into space, getting lost in the
house or yard, getting stuck in corners, and standing at the
wrong door or at the wrong side of the door to go out or in.
Dogs were considered to have an impairment in social inter-
actions if they had 2 of the following signs: a decrease in
how frequently the dog would greet its owners, a decrease in
how frequently the dog would solicit attention from its own-
ers, and a definite increase or decrease in how frequently the
dog would follow its owners around the house. Dogs were
considered to have an impairment in house training if they
started to urinate or defecate in the house without any
apparent medical or other behavioral explanation (eg, uri-
nary incontinence or separation anxiety), and there was
decreased signaling to go out, decreased use of a doggy door,
or some other change reflecting a decrease in learned house-
training behavior (eg, urinating or defecating in the house
just after coming in from outdoors). Dogs were considered
to have an impairment in the sleep-wake cycle if they had
2 of the following signs: waking up the owner at night by
some activity such as pacing or vocalizing, sleeping notice-
ably less at night, and sleeping noticeably more during the
day. In addition, dogs were considered to have impairment
in a particular category only if the associated signs had been
observed more than once a week for at least the previous
month.
Efforts were made to avoid leading the owners to expect
that there was a correct answer to any of the questions.
Before questions about specific signs associated with each
behavioral category were asked, owners were given an oppor-
tunity to provide their own open-ended comments to a gen-
eral question related to that category. During the second
interview, in addition to questions regarding signs of cogni-
tive impairment, owners were asked whether their dogs had
any evidence of visual or auditory impairments, arthritis, or
dental problems. These abnormalities did not necessarily
have to have been diagnosed by a veterinarian.
Data analysis—A cross-sectional analysis was conduct-
ed only on dogs 13 to 15 years old at the time of the second
interview to compare percentages of spayed female, castrated
male, and sexually intact male dogs with impairments in
each of the 4 behavioral categories as well as percentages of
dogs with impairments in 1 category, 1 category, and 2
categories. In a previous study,
1
a significant age by sex inter-
action was not detected for dogs with impairments in any
category. Therefore, data for dogs of all ages (13 to 15 years)
were combined, and for some analyses, percentages of
neutered dogs of both sexes with impairments were com-
pared with percentage of sexually intact male dogs.
The longitudinal analysis was performed comparing the
percentages of 11- to 14-year-old spayed female, castrated
male, and sexually intact male dogs that progressed from
having no impairments at the time of the first interview to
having impairments in 1 category at the time of the second
interview. Similarly, percentages of dogs that progressed from
having no impairments at the time of the first interview to
having impairments in 2 categories at the time of the sec-
ond interview were compared among groups, as were per-
centages of dogs that progressed from having impairments in
1 category at the time of the first interview to having impair-
ments in 2 categories at the time of the second interview.
Percentages of dogs positive for 0 or 1 sign associated with a
particular behavioral category at the time of the first inter-
view that had impairments in that category (ie, positive for
2 signs) at the time of the second interview were also deter-
mined.
The Fisher exact test or the Pearson χ
2
statistic was used
for all analyses. Values of P < 0.05 were considered signifi-
cant. Because it was hypothesized that behavioral signs of
cognitive impairment would not progress as quickly in sexu-
ally intact male dogs as in spayed female and castrated male
dogs, some tests were performed as 1-tailed tests.
Results
Prevalence of cognitive impairments among
groups—The cross-sectional analysis included 20 sex-
ually intact male dogs, 33 castrated male dogs, and 41
spayed female dogs. For each of the 4 behavioral cate-
gories, percentages of spayed female, castrated male,
and sexually intact male dogs with impairment in that
category at the time of the second interview were not
significantly different (Fig 1). However, the P value for
impairment in house training (P = 0.056) was close to
the cutoff for significance, and when spayed female
and castrated male dogs were combined, the percent-
age of neutered dogs with an impairment in house
training at the time of the second interview was signif-
icantly (P = 0.029) higher than the percentage of sexu-
ally intact male dogs with an impairment in that cate-
gory. Percentages of dogs with impairments in 1 cate-
gory, percentages of dogs with impairments in 1 cat-
egory, and percentages of dogs with impairments in 2
categories at the time of the second interview were not
significantly different among groups.
Progression of signs of cognitive impairment
This analysis involved 29 sexually intact male dogs, 47
castrated male dogs, and 63 spayed female dogs.
Twenty of the 29 (69%) sexually intact male dogs, 29
of the 47 (62%) castrated male dogs, and 34 of the 63
(54%) spayed female dogs were still alive at the time of
the second interview. The remaining 56 dogs had died
or been euthanatized prior to the second interview, but
all 56 had survived at least 6 months after the first
interview. Mean follow-up time for all 139 dogs in the
study (ie, mean time from the first to the second inter-
view or mean time from the first interview to time of
death) was 15.3 months (SD, 2.6 months). Mean age at
which spayed female dogs had been spayed was 2.8
years (SD, 0.1); mean age at which castrated male dogs
had been castrated was 4.8 years (SD, 1.2). At the time
of the first interview (ie, when dogs were 11 to 14 years
old), 41 of the 63 (65%) spayed female dogs did not
have impairments in any of the behavioral categories,
18 (29%) had impairments in 1 category, and 4 (6%)
had impairments in 2 categories. Thirty-two of the 47
(68%) castrated male dogs did not have impairments in
Figure 1—Percentages of dogs between 13 and 15 years old
that had impairments in each of 4 behavioral categories associ-
ated with cognitive function and that had impairments in 1 cat-
egory, 1 category, or 2 categories. FS = Spayed female. MC
= Castrated male. MI = Sexually intact male.
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54 Scientific Reports: Original Study JAVMA, Vol 219, No. 1, July 1, 2001
SMALL ANIMALS/
EXOTICS
any of the behavioral categories, 9 (19%) had impair-
ments in 1 category, and 6 (13%) had impairments in
2 categories. Nineteen of the 29 (66%) sexually intact
male dogs did not have impairments in any of the
behavioral categories, 6 (21%) had impairments in 1
category, and 4 (13%) had impairments in 2 cate-
gories.
For all groups, between 27 and 41% of dogs that
did not have any impairments at the time of the first
interview had impairments in 1 category at the time
of the second interview, and approximately 10% had
impairments in 2 categories. Analysis of the percent-
ages of dogs progressing from impairments in 0 cate-
gories at the time of the first interview to impairments
in 1 category at the time of the second interview and of
dogs progressing from impairments in 0 categories at
the time of the first interview to impairments in 2
categories at the time of the second interview did not
reveal any significant differences among groups (Fig 2;
P = 0.124 to 1.00).
Of the 18 spayed female dogs with impairments in
1 category at the time of the first interview, 9 (50%)
had impairments in 2 categories at time of the second
interview. Of the 9 castrated male dogs with impair-
ments in 1 category at the time of the first interview,
4 (44%) had impairments in 2 categories at time of
the second interview (1 of these castrated males
improved to no impairments on the second interview).
By contrast, none of the 6 sexually intact male dogs
with impairments in 1 category at the time of the first
interview had impairments in 2 categories at time of
the second interview (Fig 2). Percentages of dogs pro-
gressing from impairments in 1 category at the time of
the first interview to impairments in 2 categories at
the time of the second interview were not significantly
different between spayed female and castrated male
dogs (P = 0.512). Numbers of dogs were too small to
allow comparisons between sexually intact male dogs
and castrated male dogs or spayed female dogs.
However, when castrated male and spayed female dogs
were combined, the percentage of sexually intact male
dogs that progressed from impairments in 1 category at
the time of the first interview to impairments in 2
categories at the time of the second interview was sig-
nificantly less (1-tailed Fisher exact test, P = 0.035;
2-tailed Pearson χ
2
statistic, P = 0.03) than the per-
centage of neutered dogs that progressed.
The difference between sexually intact male dogs
and neutered dogs was not attributable to a major dif-
ference in age of the dogs at the time of the first inter-
view, as 14 of the 29 (49%) sexually intact male dogs,
25 of the 47 (53%) castrated male dogs, and 37 of the
63 (59%) spayed female dogs were 11 to 12 years old
at the time of the first interview. The difference was
also not a reflection of major differences in follow-up
time. Mean follow-up times for spayed female, castrat-
ed male, and sexually intact male dogs with impair-
ments in 1 behavioral category at the time of the first
and second interviews were 13.1 months (SD, 5.3
months; n = 9), 17.0 months (SD, 2.1 months; 4), and
17.0 months (SD, 2.8 months; 6), respectively. Mean
follow-up times for spayed female and castrated male
dogs that progressed from impairments in 1 behavioral
category at the time of the first interview to impair-
ments in 2 categories were 16.3 months (SD, 5.2
months; n = 9) and 15.9 months (SD, 0.8 months; 4),
respectively.
Percentages of dogs with visual and hearing
impairments, arthritis, or dental problems did not dif-
fer between sexually intact male dogs and neutered
dogs. Of the 6 sexually intact male dogs with impair-
ments in 1 behavioral category at the first and second
interviews, 4 (67%) had arthritis, 1 (17%) had dental
disease, 5 (83%) had visual impairments, and 5 (83%)
had hearing impairments. Of the 13 neutered dogs
with impairments in 1 behavioral category at the first
and second interviews, 6 (46%) had arthritis, 1 (8%)
had dental disease, 10 (77%) had visual impairments,
and 12 (92%) had hearing impairments. Of the 13
neutered dogs that progressed from impairments in 1
behavioral category at the time of the first interview to
impairments in 2 categories at the time of the second
interview, 5 (38%) had arthritis, 6 (46%) had dental
disease, 11 (85%) had visual impairments, and all 13
(100%) had hearing impairments. Although these
problems were not necessarily verified by examination
by a veterinarian, results suggest that differences
between sexually intact male and neutered dogs were
likely attributable to differences in cognitive function
and not a reflection of the owners’ perceptions of their
dogs’ overall health.
Discussion
Results of previous studies
1,8
of behavioral
changes in aging dogs performed at the same institu-
tion as the present study indicated that abnormalities
in 4 behavioral categories (disorientation in the
home and yard, disturbances in social interactions,
impairment of house training, and disruption of the
sleep-wake cycle) can be evaluated by use of a struc-
tured telephone interview format. These behavioral
signs presumably reflect disruptions of cognitive
function, have a gradual onset, and progress over
time. All 4 of these behavioral categories involve
learning or memory in one way or another, and signs
associated with these categories comprise most of the
behavioral signs improved by use of selegiline in
aging dogs.
7
Figure 2—Percentages of dogs 11 to 14 years old that pro-
gressed, over a period of 6 to 18 months, from not having
impairments in any behavioral category to having impairments in
1 category or to having impairments in 2 categories and that
progressed from having impairments in 1 behavioral category to
having impairments in 2 categories.
See
Figure 1 for key.
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JAVMA, Vol 219, No. 1, July 1, 2001 Scientific Reports: Original Study 55
SMALL ANIMALS/
EXOTICS
In the present study, the percentage of sexually
intact male dogs with impairments in house training at
the time of the second interview (ie, when dogs were
13 to 15 years old) was significantly less than the per-
centage of neutered dogs. No other differences between
groups were detected at the first or second interview;
however, the low percentages of dogs with impair-
ments in any particular category may have precluded
detection of differences.
When results for the first and second interviews
were compared, there were no significant differences
among groups in regard to percentages of dogs that
progressed from not having any impairments to having
impairments in 1 category or to having impairments in
2 categories. However, percentage of dogs that pro-
gressed from being mildly impaired (ie, impairments in
1 behavioral category) at the time of the first interview
to being severely impaired (ie, impairments in 2 cat-
egories) at the time of the second interview was signif-
icantly higher for neutered than sexually intact male
dogs. Thirteen of the 27 (48%) neutered dogs pro-
gressed from being mildly impaired to being severely
impaired, whereas none of the 6 sexually intact male
dogs did.
There were not any differences among groups in
regard to prevalence of owner-reported visual or hear-
ing impairment, arthritis, or dental problems suggest-
ing that owners of sexually intact male dogs did not
perceive their dogs as being in better overall health.
Also, there were no differences among groups in regard
to age or follow-up time that could explain the differ-
ence between sexually intact male and neutered dogs.
Thus, the difference in percentage of dogs that pro-
gressed from mild to severe impairment was likely a
reflection of hormone-related differences in cognitive
function, suggesting that the presence of circulating
testosterone in the sexually intact male dogs may have
slowed the progression of cognitive impairment in
dogs that already had signs of mild impairment. This
finding is in line with current research on the neuro-
protective roles of testosterone and estrogen at the cel-
lular level and the role of estrogen in preventing
Alzheimer’s disease in human females. One would pre-
dict that estrogens would have a similar protective role
in sexually intact female dogs; unfortunately, too few
sexually intact female dogs were available for inclusion
in the present study to test this hypothesis.
Clearly, more work is needed to confirm and extend
these findings. While the veterinary community is wait-
ing for additional research on this subject to be per-
formed, the implications of these findings on the prac-
tice of early spaying and neutering of dogs that are kept
into their senior years as family companions should be
considered. First, it should be pointed out that only a
small percentage of dogs progress to the level of severe
cognitive impairment. Thus, the risk associated with
loss of the protective effects of gonadal hormones may
be a small price to pay for the advantages of gonadecto-
my (eg, prevention of ovarian, uterine, and testicular
cancer). For some dog owners, however, the increased
likelihood of progression to severe cognitive impairment
may be more of a concern, particularly given the higher
prevalence of impairments in house training among
neutered dogs, compared with sexually intact male dogs.
It may also be a concern in working dogs for which a
high level of cognitive function is required, such as
those used for police work, to provide assistance to the
disabled, and for scent detection.
Results of the present study may also stimulate a
search for alternative means of fertility control that
leave gonadal hormone production intact. Tubal
(oviduct) ligation could be used in females and vasec-
tomy could be used in males, but both of these proce-
dures have drawbacks, in that female dogs that under-
go tubal ligation will still cycle into estrus and will not
be protected from uterine disease or mammary cancer,
and male dogs that undergo vasectomy would not
receive the advantages of decreased likelihood of prob-
lem aggression, urine marking, and sexual behavior
associated with castration.
52
Alternatively, the benefits
of hormonal replacement therapy in senior gonadec-
tomized male and female dogs should be determined,
or the benefits of prophylactic treatment with appro-
priate drugs to reduce the likelihood of cognitive
impairment should be investigated.
a
Anipryl, Pfizer Animal Health, Exton, Pa.
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... In cooperation with Hsu in 2005, Sarpol found that castrated male cats have better learning-teachableability than non-castrated male cats (Starling et al., 2019). Later studies proved this significant relationship with a lower level of PLGH (Hart, 2001). Hart (2001) suggested that castration increases the risk of cognitive dysfunction in older male cats (Scandurra et al., 2018). ...
... Later studies proved this significant relationship with a lower level of PLGH (Hart, 2001). Hart (2001) suggested that castration increases the risk of cognitive dysfunction in older male cats (Scandurra et al., 2018). Subsequent studies found that castration is associated with the reduction of social and cognitive relationships (Eiland and Romeo, 2013). ...
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Tazerji SS, Vazir B, Kabir F, Duarte PM and Akhtardanesh B (2024). Investigating the Possible Effect of Neutering on Cat Behaviour. Journal of Immunology Immunopathology, 26(1): 64-69. Cat castration is one of the most common conventional surgeries in veterinary clinical medicine. In females, this surgery can be performed while removing both ovaries along with the uterus (ovariohysterectomy) or only removing the ovaries (ovariectomy). Accordingly, the present study investigates the possible effect of castration on cat behaviour. After collecting data from reliable national and international scientific databases, a questionnaire was prepared. Based on Cochran's statistical relationship, 192 national and international questionnaires about pets were completed and the statistical results were analysed in SPSS-24 software. Based on the results, the factors of weight, sexual cycle, and keeping other pets do not play a role in the occurrence of different behaviours in cats. However, the factors of castration of cats, sex, age, time of castration, and place of keeping cats play a role in the occurrence of different behaviours. Also, analysing the effect of castration on the behaviour of cats also showed that cats behaved differently before and after castration. The study showed that castration significantly reduces unwanted behaviours and practical management while promoting responsible pet ownership.
... a) Sex and castration/neutering Hart (2001) suggested that sex hormones may play a role in preventing the development of cognitive impairment (and consequently, behavioural changes) in dogs associated with age. ...
... Neutered dogs, especially dogs of larger breeds, also had more difficulty with movement, which is probably related to their frequent high weight. Also, studies have shown (Urfer and Kaeberlein, 2019;Hart, 2001) that the presence of circulating testosterone in sexually intact dogs can slow down the progression of cognitive impairment in dogs that have already shown signs of moderate impairment. Similarly, oestrogens may also have a protective role, as demonstrated in studies of Alzheimer's disease in women (Austad, 2019;Sano et al., 1997;Haskell et al., 1997), but we did not find differences in cognitive changes. ...
... This suggests that long-term gonadal steroid deprival could eventually have detrimental effects on GnRH neuronal function and, because brain GnRH release plays a vital role in controlling mental and sensory abilities (Manfredi-Lozano et al., 2022), it may accelerate cognitive decline (Karlamangla et al., 2017;Santoro et al., 2021), as suggested by preclinical findings in mice (Anckaerts et al., 2019;Kara et al., 2021;Manfredi-Lozano et al., 2022), and may thus be a risk factor for dementia. In dogs, there is some evidence suggesting that gonadectomy increases the risk of cognitive dysfunction in both sexes (Azkona et al., 2009), and increases the speed of progression from mild to more severe cognitive impairment in male dogs (Hart, 2001). From the preclinical and clinical data obtained in mice and in men (Manfredi-Lozano et al., 2022), respectively, it could be expected that the implantation of a programmable minipump releasing one pulse every 2-3 h to mimic the GnRH/LH secretory pattern during the luteal phase in bitches (Concannon, 2012;Kooistra et al., 1999), or in males (Enright et al., 2010), protects cognitive functions in these pets by stimulating neocortical GnRHR expressing neurons at a physiological pace and hence compensate the potential exhaustion of GnRH neuronal function induced by longterm gonadectomy . ...
... Patients with Alzheimer's disease also show olfactory deficits, as in the case of other neurodegenerative diseases (Doty, 2012). In resonance with the previous section, gonadectomized dogs appear to be more likely to show signs of CDD than intact dogs (Azkona et al., 2009;Hart, 2001). This, together with the fact that the human literature suggests that men receiving androgen deprivation therapy, that is GnRH agonists, for prostate cancer, may be prone to accelerated cognitive decline and have a higher risk of developing dementia and Alzheimer's disease than controls (Cherrier & Higano, 2020;Sharifi et al., 2005), it could be hypothesized that altered brain GnRH signalling may play, at least in part, a role in this process. ...
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Pulsatile secretion of gonadotropin-releasing hormone (GnRH) is essential for the activation and maintenance of the function of the hypothalamic-pituitary-gonadal (HPG) axis, which controls the onset of puberty and fertility. Two provocative recent studies suggest that, in addition to control reproduction, the neurons in the brain that produce GnRH are also involved in the control postnatal brain maturation, odor discrimination and adult cognition. Long-acting GnRH antagonists and agonists are commonly used to control fertility and behavior in veterinary medicine, primarily in males. This review puts into perspective the potential risks of these androgen deprivation therapies and immunization on olfactory and cognitive performances and well-aging in domestic animals, including pets. We will also discuss the results reporting beneficial effects of pharmacological interventions restoring physiological GnRH levels on olfactory and cognitive alterations in preclinical models of Alzheimer's disease, which shares many pathophysiological and behavioral hallmarks with canine cognitive dysfunction. These novel findings raise the intriguing possibility that pulsatile GnRH therapy holds therapeutic potential for the management of this behavioral syndrome affecting older dogs.
... Additionally, neutering of dogs and is promoted for population control and behavior modification (1). On the other hand, numerous recent publications have been shown that gonadectomy increases the risk of musculoskeletal degenerative diseases (e.g., hip dysplasia, cranial cruciate rupture), obesity and associated diseases, several forms of cancer, some immune-mediated diseases, urinary incontinence and cognitive dysfunction syndrome (3,4,(7)(8)(9)(10)(11). All these diseases associated with gonadectomy may require ongoing care and treatment, intermittent monitoring and protection. ...
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Gonadectomy, commonly known as neutering, is widely used to address dog overpopulation and reduce reproductive disease risks, such as mammary cancer and pyometra. It is also advocated for behavior modification. However, neutering is associated with an increased risk of certain musculoskeletal disorders, obesity, several types of cancer, immune-mediated diseases, and cognitive dysfunction. These conditions may necessitate ongoing care and treatment, that require special care that the caregiver must provide furthermore burdens the caregiver with daily tasks, which encompasses the emotional, physical, social, and financial impact on pet owners caring for chronically ill animals. This burden can result in burnout, health issues, depression, social isolation, and financial stress. The potential benefits and risk of gonadectomy can affect the quality of life of both humans and pets. Relevant research findings should therefore be incorporated into each pet's and owner's particular situation. The purpose of this review is to address the long-term neutering risks and the potential caregiver burden that arises from these risks.
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Recent reports have suggested that β-amyloid (Aβ) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length Aβ423 fragments (i.e., Aβ forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both Aβ423 and Aβ40 (Aβ forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential Aβ deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of Aβ immunoreactive plaques, using antibodies to Aβ1–17, Aβ17–24, Aβ1–28, Aβ40, and Aβ42. We report that plaques within the canine and feline brain are immunopositive for Aβ42 but not Aβ40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within Aβ1–17, Aβ17–24, and Aβ1–28. In all species examined, vascular deposits were immunopositive for both Aβ40 and Aβ42. In the human brain, diffuse plaques were preferentially Aβ42 immunopositive, while neuritic plaques and vascular deposits were both Aβ40 and Aβ42 immunopositive. However, not all neuritic plaques contain Aβ40 epitopes.