The Journal for Nurse Practitioners xxx (xxxx) xxx

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The Journal for Nurse Practitioners

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Case Report

Depression in a Patient With Alzheimer Disease

Ann Lurati

a b s t r a c t
Keywords: This is a case study of a 73-year-old woman recently diagnosed with Alzheimer disease living in an assisted
Alzheimer disease living facility who presented to an outpatient behavioral health clinic with her son for evaluation and
apathy
treatment of depression. This article highlights the presentation of depression (a diagnosis) versus apathy (a
depression
selective serotonin reuptake inhibitors
symptom of Alzheimer disease) and the need to assess for co-occurring mood disorders that warrant
pharmacologic intervention as well as treatment for cognitive decline in Alzheimer disease.
© 2022 Elsevier Inc. All rights reserved.

This is a case study of a 73-year-old woman with the chief
complaint of “I am so sad!”
History of Present Illness
S.D. is a 73-year-old woman who presented to an outpatient
behavioral health clinic for evaluation and treatment of depressive
symptoms. S.D. was diagnosed with Alzheimer disease 1 year ago.
Her sons became concerned when SD was not paying her bills on
time. S.D. was a widow; her husband died 2 years earlier. S.D.’s sons
also witnessed their grandmother’s memory decline and saw the
same patterns in their mother. Once S.D. was diagnosed with Alz-
heimer disease, the patient as well as the sons decided S.D. should
discontinue driving; her sons took her to the supermarket for
groceries and took her to her medical appointments. S.D. also lived
in a 2-story home and had experienced several falls when walking
up and down the stairs. Her sons also drove her to church functions
as well as ensuring that there were frequent visits by friends and
relatives. However, S.D. continued to be functionally independent
with activities of daily living.
S.D. underwent formal neuropsychiatric testing, which revealed
an early stage of Alzheimer disease. The neurologist prescribed
donepezil 5 mg with a titrated dose of 10 mg daily. During the last
visit in March 2021, the son reported there was no change in his
mother’s cognitive abilities, so the provider added memantine 5 mg
and increased the dosage to 10 mg twice a day. There was some
gastrointestinal upset, but these symptoms subsided. The sons,
fearing that their mother may injure herself, became her legal
guardians. S.D. reluctantly agreed to sell her home and move into
an assisted living facility (ALF) but developed a sense of hopeless-
ness due to a loss of independence and an uncertain future
associated with the diagnosis of Alzheimer disease.
Upon arrival at the ALF, S.D. started showing symptoms of sadness
according to her sons. S.D. no longer wanted to attend church services
or social functions, indicating anhedonia. Her sons stated that they
had purchased S.D. a computer so that she could connect with her
friends and relatives via Zoom as well as attend church services on-
line. The social worker at the ALF assisted S.D. in using the computer
and accessing Zoom. However, S.D. was not interested in socializing,
saying “What’s the point! I am going to die anyway.” S.D. also stated
that “I do not want anyone to see me like this; I will be nothing but a
vegetable.” S.D. lost 5 pounds in 1 month, stating “I’m not that
hungry.” When the nursing staff asked S.D. about the quality of her
life, she said “I am so angry that I am here! How could I sleep? Be-
sides, I ache all over.” S.D.’s sons and the nursing staff at the ALF
described S.D.’s mood as “irritable.” Sometimes, S.D. stated that she
could not concentrate. For example, when trying to read a newspaper,
S.D. stated “I just keep thinking about how someday I may not be able
to read, due to my Alzheimer disease.”
Her sons relayed that in the past S.D. was full of energy, describing
how she would walk about 2 to 3 miles a day. However, since moving
into the ALF, she seemed to be “not full of energy, the way she used to
be,” and S.D. complained of generalized fatigue. S.D. continued to
shower and perform her daily hygiene, such as brushing her teeth.
S.D. used to enjoy reading; however, when asked what she would like
to read, she responded “What’s the point?”
S.D. denied any hallucinations, obsessive-compulsive disorder
tendencies, manic episodes, phobias, panic attacks, paranoid thoughts,
or past traumas. She reported no issues with sleep. After a follow-up
visit with neurology, it was recommended that S.D. be evaluated and
treated for possible depression. S.D. and her son stated the goal of the
visit was to “overcome this sadness,” with S.D. stating “I know that
Alzheimer disease has a poor prognosis, but I want to make the most of
my time here on earth as productive as possible.” She and her son were
willing to try medications as well as other treatment modalities.

https://doi.org/10.1016/j.nurpra.2022.05.003
1555-4155/© 2022 Elsevier Inc. All rights reserved.
2 A. Lurati / The Journal for Nurse Practitioners xxx (xxxx) xxx
Review of Systems
The review of systems revealed weight loss of 10 pounds in 3
months and a diagnosis of Alzheimer disease 2 years ago.
History of Substance Use
The patient denied any use of alcohol, nicotine products, or any
legal or illegal controlled substances.
Past Medical History
S.D.’s past medical history included hypertension and elevated
cholesterol.
Medications
The patient indicated that she was taking the following medi-
cations: lisinopril 10 mg orally daily, Lipitor (atorvastatin calcium;
Viatris) 20 mg orally daily, aspirin 81 mg orally daily, donepezil 10
mg orally daily, and memantine 10 mg orally twice a day.
Family/Social History
The family history included her mother who was diagnosed
with Alzheimer disease and died at age 82. S.D. was married for 60
years and has 2 sons. Her husband passed away 2 years prior; both
were active members of the Mormon Church. She graduated from a
4-year university when she was 21 years old and has a degree in
education.
Past Psychiatric History
She reported a history of “baby blues” with both children.
However, she was never formally diagnosed with postpartum
depression.
Physical Examination
The patient presented as a thin but well-nourished female. The
neurologic examination revealed no abnormalities.
Mental Status Examination
The patient is a calm and quiet female with slow psychomotor
response at times; her orientation was adequate, and she denied any
suicidal ideations. Regarding cognition, her remote memory was
intact, she had a recent word recall of 1 out of 3, she was unable to
spell “world” backward, and her attention decreased; she needed
breaks every 15 minutes during the interview. She was able to
calculate 2  2 and understood abstract concepts (eg, kill two birds
with one stone). She is a good historian for long-term memories and
remembers family and friends; however, she could not remember the
name of examiner, even when introduced several times. For
comprehension, she was able to follow directions, but if the directions
involved 3 or more steps, she was unable to do it. The patient un-
derstood how to use a “key” and was able to name a “pencil.”
Laboratory Tests and Imaging
A complete blood count, a comprehensive metabolic panel with
magnesium, a thyroid panel, urinalysis, vitamin D and B levels, and
human immunodeficiency virus and syphilis testing were per-
formed by her primary care provider in March 2021; there were no
abnormalities. Brain magnetic resonance imaging with and without
Table
Neuropsychometric Testing
Baseline 4 Months After Treatment
PHQ-9 16/27 11/27
MoCA 21/30 2030
GAD-7 11/21 9/21
MMSE 22/30 20/30
contrast in March 2021 indicated amyloid plaques and neurofi-
brillary tau proteins were present, but they were stable compared
with testing performed in March 2020. There were no abnormal-
ities on electroencephalography. Her cerebral spinal fluid (ordered
by neurology) was positive for tau proteins.
Structured Neuropsychiatric Instrument Results
The patient’s structure neuropsychiatric instrument results
were as follows (Table):
 Generalized Anxiety Disorder 7 (GAD-7): 11 out of 21, indicating
moderate generalized anxiety
 Patient Health Questionnaire-9 (PHQ-9): a score of 16 out of 27,
indicating moderate depressive symptoms
 Montreal Cognitive Assessment Scale (MoCA): a score of 21 out
of 30, indicating mild Alzheimer disease
 Mini-Mental State Examination (MMSE): a score of 22 out of 30,
indicating possible cognitive impairment
Differential Diagnoses
Major Depressive Disorder: Moderate Symptoms (296.31 [F33.0])
The patient has risk factors for depression, which include the
loss of a spouse, the beginnings of Alzheimer disease with a loss of
cognitive ability, a loss of independence, insomnia, and complaints
of generalized pain. There may be a history of untreated or undi-
agnosed postpartum depression as well as a family history of
Alzheimer disease in females. The patient has a history of
well-controlled hypertension (being treated with lisinopril, an
angiotensin-converting enzyme inhibitor that has been associated
with depression). The patient complained of sadness, a lack of
motivation, and anhedonia and does not read or socialize; these
were activities that she enjoyed in the past. She also complained of
a decreased appetite with weight loss. The patient expressed
thoughts of “I do not want to be a burden” and slow psychomotor
activity. She reported a loss of energy and that she was unable to
concentrate due to intrusive thoughts. These symptoms caused
distress in socialization. The patient stated that her depressive
symptoms started after the diagnosis of Alzheimer disease and
worsened when she moved into the ALF. S.D. also complained of
generalized pain. She indicated that she does worry about her
physical health but is tearful, irritable, and angry at times. The
patient denied any symptoms of obsessive-compulsive disorder,
bipolar disorder, posttraumatic stress disorder, or hallucinations or
paranoid thoughts. Neuropsychological testing revealed mild
depression. Additional testing such as the PHQ-9 indicated major
depressive symptoms. However, the patient did not express guilt
and has strong religious beliefs; she also has a strong support
network. The patient continues with self-care activities. Her
depressive symptoms may be associated with Alzheimer disease.
S.D. exhibits apathy (such as diminished motivation); however, the
patient shows goal-directed behavior and has an emotional
response, whereas if the diagnosis was strictly Alzheimer disease,
she may be indifferent or show apathy. Declining cognitive deficits,
 A. Lurati / The Journal for Nurse Practitioners xxx (xxxx) xxx
short-term memory loss, and eventually long-term memory loss
are more associated with Alzheimer disease than depression. Alz-
heimer disease may present with apathy-type behavior. However,
S.D. reveals emotions such as anhedonia, anger, and irritability at
times, which are more consistent with depressive symptoms than
apathy in Alzheimer disease.
Major Neurocognitive Disorder: Specify Alzheimer DiseasedMild
Form (331.0 294.1x F02.8x)
The patient is experiencing decreased cognitive decline in
complex attention and executive functioning as per the MoCA and
MMSE. However, currently, her long-term memory is intact. The
patient’s sons reported a loss of cognitive ability, with magnetic
resonance imaging and neuropsychological testing revealing Alz-
heimer disease. There is a positive family history of Alzheimer
disease (the patient’s mother).1 There is a history of hypertension,
which is well controlled. There is evidence of short-term memory
decline when the patient became lost when driving and was unable
to pay bills. The cognitive deficits did not occur due to acute
delirium. The patient is functionally independent; however, she
does not cook. Depression may exacerbate or worsen cognitive
abilities in patients with Alzheimer disease. However, generalized
pain, insomnia, and decreased appetite are not typical early
symptoms of Alzheimer disease; instead, these may be symptoms
of depression.
Generalized Anxiety Disorder (300.02 [F41.1])
The patient worries about the decline of her life due to Alz-
heimer disease. She stated that she cannot control worry and finds
it to be intrusive into her activities, such as reading. She reported
that she experiences fatigue, sleep disturbances, difficulty in con-
centration, and irritability at times. The anxiety interferes with her
social and family functions and is not attributable to a substance or
medication. However, the anxiety could be associated with Alz-
heimer disease. She stated that her anxiety is associated with a
possible functional decline, which is realistic, as well as anxiety
associated with living in an ALF and not her home. She complained
of generalized pain that may be related to muscle tension. She also
reported some social anxiety and not wanting others to notice any
cognitive decline. She expressed that her anxiety concerns are
associated with health decline and a loss of independence and not a
specific concern, but she indicated that she does have somatic pain.
Generalized pain may be associated with muscle tension with ad-
ditive effects of mild arthritis, which is notable in the hands. The
patient indicated she is not anxious about “catching a disease” nor
did she report anxiety associated with meeting people. She stated
that “I just don’t feel like socializing.” She denied any phobias or
panic attacks.
Discussion
Mood Disorders in Alzheimer Disease
Alzheimer disease is a neurodegenerative disorder that includes
changes in mood, such as apathy and depression.2 Alzheimer dis-
ease involves diminishing levels of acetylcholine that impair
cortical cholinergic function and increased levels of glutamate, a
neurotransmitter that is considered to be excitatory that leads to
the overproduction of glutamate, which may lead to neural damage
that affects memory and learning.3 Neural changes in Alzheimer
disease reveal the formation of amyloid plaques and neurofibrillary
tangles.4
3
Alzheimer disease is associated with deficits in memory and
associated executive functions; there are mood changes that occur
as well. Apathy and major depressive disorder may be present.
Symptoms of apathy and major depressive disorder are trans-
diagnostic and may be difficult to distinguish. Symptoms of poor
concentration and irritability may be present in apathy and major
depressive disorder. Both mood disorders may present as func-
tional decline.5
Apathy is the absence of any emotion, and similar depressive
symptoms can lead to a decline in functional capacity. There is a
lack of motivation to engage in self-care or to engage with the social
environment.5 Apathy in Alzheimer disease may be linked to dys-
regulation of dopamine and serotonin. Apathy may be difficult to
treat; however, major depressive disorder is treatable.
On the other hand, with major depressive disorder, the patient
may express sadness and hopelessness. There is a dysregulation of
the serotonergic system, which leads to symptoms of depression
and anxiety. Appetite changes, generalized pain symptoms, and
early changes in sleep patterns may be stronger indicators of
depression. Pain and depression commonly coexist because both
involve the dysregulation of serotonin and norepinephrine neuro-
transmitters.6 The sensation of pain may be more related to
symptoms of depression versus apathy. If left untreated, depression
may accelerate the rate of cognitive impairment.7
To assist in diagnostic reasoning, the use of structured neuro-
psychiatric instruments, such as the PHQ-9 and the GAD-7, may
assist in the differential diagnoses in the primary care setting.8 Both
the PHQ-9 and GAD-7 reflect the symptoms of depressive disorder
and anxiety disorder based on the Diagnostic and Statistical Manual
of Mental Disorders, Fifth Edition. The MoCA and the MMSE can be
used for the assessment of cognitive impairment.1 The MoCA and
MMSE can also be used for monitoring purposes.8,9 The MMSE
assesses visuospatial and executive function.8 The MoCA assesses
memory, language, executive function, visuospatial abilities, praxis,
and attention.9 To assess pain levels in patients with Alzheimer
disease, the Pain Assessment in Advanced Dementia may be used.10
This is an observational tool that assesses breathing patterns,
negative vocalizations, facial expressions, body language, and
consolability.
Medications
Memantine and donepezil can be used in combination in the
treatment of early Alzheimer disease and may improve symptoms
of both apathy and depression.2 Donepezil prevents the breakdown
of acetylcholine, and memantine decreases the production of
glutamate. Glutamate acts on the N-methyl-D-aspartate (NMDA)
receptor, which is involved in learning and memory. When there is
increased stimulation of NMDA receptors, ischemia may occur.
Memantine is considered neuroprotective and blocks the actions of
glutamate on the NMDA receptors.
The starting dose of memantine extended release is 7 mg orally
and can be titrated up to 28 mg for a maintenance dose with
donepezil hydrochloride of 10 mg orally. Titration may take up to 7
weeks. The patient may experience gastrointestinal upset, so pa-
tient education includes taking the medication with food and
monitoring for diarrhea, which can lead to dehydration. Long-term
use may increase the risk of falls and dizziness. It is advisable not to
discontinue both medications abruptly; slow tapering is recom-
mended over weeks.
Apathy may be treated with a second-generation atypical anti-
psychotic. However, extreme caution is warranted when prescrib-
ing antipsychotic medications in patients with Alzheimer disease
and should only be prescribed at low doses and for a limited length
of time.1 Antipsychotic medications are associated with an
4 A. Lurati / The Journal for Nurse Practitioners xxx (xxxx) xxx
increased risk of cognitive decline and cardiovascular disease.1
Donepezil also can reduce symptoms of apathy.11
Selective serotonin reuptake inhibitors (SSRIs) used to treat
depression can also contribute to symptoms of apathy as well.11
Depression can be treated with SSRIs. The use of SSRIs, specifically
citalopram, has been shown to slow the formation of amyloid-b in
humans.7
However, vortioxetine is a newer SSRI that targets the 5-HT₁ A
serotonin system7; 5-HT1A is involved in mood and cognition. One
study showed that after a 12-month trial vortioxetine improved
symptoms of depression and improved cognition.7 The medication
is an agonist that works directly on the 5-HT 1A receptor site that
enhances the effects of serotonin on the neural tissue. By enhancing
the effects of serotonin, there is also increased production of
norepinephrine, dopamine, acetylcholine, histamine, and
gamma-butyric acid and a decrease in glutamate.7 The release of
norepinephrine improves mood and brain activity, and dopamine
improves symptoms of anhedonia. Vortioxetine may also reduce
pain symptoms associated with major depressive disorder.12 Pain is
influenced by the 5-HT system. Vortioxetine may block pain signals
on certain areas of the 5-HT system while acting as an agonist on
others and leading to the improvement of pain symptoms and
improving mood.12
The side effects of vortioxetine include nausea and headache.
The initial dosing is 5 to 10 mg once a day, and the daily dose may
be increased based on response and tolerability in increments of 5
to 10 mg at 1-week increments with a maximal dose of 20 mg once
daily. Vortioxetine carries the risk of increased bleeding and oste-
oporosis. If the medication needs to be discontinued, taper doses
slowly over several weeks to avoid withdrawal symptoms such as
insomnia, shocklike sensations, and gastrointestinal symptoms.
Consideration can be made for taking vortioxetine in the morning
because some SSRIs may interfere with sleep quality. However,
vortioxetine is considered to have less of an impact on sleep
compared with other SSRIs.12
Adjunct Therapies
Proper sleep enhances memory consolidation, whereas sleep
disturbances accelerate cognitive decline.12 Adequate sleep may be
defined as feeling refreshed in the morning without fatigue.13 As
Alzheimer disease progresses, sleep disturbances become more
frequent.14 Inadequate sleep may contribute to inflammatory
markers such as C-reactive protein and interleukin-6, which may
accelerate the formation of amyloid-b as well as impair the removal
of neurotoxic by-products. Adequate sleep is also associated with
elevated levels of brain-derived neurotrophic factor (BDNF).15
Aerobic and anaerobic exercise may slow the progression of disease
and improve sleep.16 Exercise increases the production of BDNF to
improve nerve regeneration and vascular endothelial growth factor
to enhance blood oxygen levels.17 Exercise may also inhibit neural
apoptosis and inhibit oxidative stress with enhanced autophagy.17
Physical exercise also increases levels of dopamine, serotonin, and
g-aminobutyric acid (GABA) as well as regulates levels of glutamate
and norepinephrine.17
Exercise decreases the activity of the hypothalamic-pituitary-
adrenal axis, which is associated with stress, as well as enhances
the effects of the parasympathetic nervous system to promote
relaxation. There is evidence that exercise activates the endo-
cannabinoid system that modulates pain and emotions.18 Exercise
may also increase bone strength, improve gait and balance, and
therefore decrease the risk of falls.17 Exercise also decreases
neuropathic pain.17
Music therapy may have positive effects on cognition, mood,
and immunity.19 Listening to calming music can stimulate areas of
the cortical and subcortical levels of the brain. Pleasing music also
has positive effects on the limbic system. There appears to be
increased levels in blood oxygen as well as neural activation by
enhancing the production of BDNF. Glutamate levels have
decreased as well. Calming music may also enhance the activities of
natural killer cells, lymphocytes, and interferon gamma. The im-
mune system responds by decreasing inflammatory cytokines in
the central nervous system and the cardiovascular system.
Medications and adjunct therapies may be considered when
treating major depressive disorder as well as symptoms of apathy
in patients with Alzheimer disease. Apathy can be a symptom of
depressive disorder and/or Alzheimer disease.20 Apathy involves a
lack of interest in different aspects of life, including normal daily
tasks and social activities. Apathy versus depressive disorder is
characterized by feelings of indifference and a lack of emotion.
Apathy may involve the following distinct subtypes: emotional,
behavioral, and social motivation. There are several scales available
to screen for apathy, such as the Apathy-Motivation Index and the
Lille Apathy Rating Scale.20
Conclusion
S.D. is suffering from major depressive disorder. The secondary
diagnosis is early Alzheimer disease. She is also experiencing
generalized anxiety. Depression is associated with a loss of inde-
pendence and a loss of home, being forced to move into an ALF, and
cognitive decline. However, the family and patient are willing to try
medications to see if her anger, irritability, concentration, and so-
cialization improve. The plan was to begin a trial of vortioxetine
because it is associated with improving executive function and an
improved safety profile. The initial dose was 5 mg orally once a day
(for elderly), titrating her dose every week to aim for a maintenance
dose of 5 to 20 mg orally once a day. The maximum dose is 20 mg/d.
The patient also continued her donepezil 10 mg orally daily and
memantine 10 mg orally twice a day. The neurologist explained to
the son and patient that she was to remain on the memantine for
the duration of her life. Discontinuing the medication would result
in further cognitive decline, which cannot likely be regained if
memantine was restarted. The patient was instructed to take the
medication with food to decrease gastrointestinal side effects, and
her mood and concentration abilities will be monitored. There are
no drug-drug interactions noted with donepezil and memantine.
Lisinopril requires continued monitoring of kidney function and
blood pressure. Pain may be associated with depressive and anxiety
symptoms. Pain levels were to be monitored by the Pain Assess-
ment in Advanced Dementia Scale.
Depressive and anxiety levels need to be monitored to deter-
mine if there is an improvement with comorbidity pain levels. The
patient began cognitive behavioral therapy to address cognitive
distortions, to develop coping skills, and to improve socialization.
The patient was also referred to group therapy to improve family
relationships and socialization skills. The PHQ-9 and GAD-7 were
also used to monitor mood and anxiety. To monitor the progression
of Alzheimer disease, the MoCA and the MMSE were used. Music
therapy was also considered to improve mood as well as the
implementation of sleep hygiene practices and monitoring sleep.
Occupational therapy assisted with activities of daily living with
hand therapy for symptoms of osteoarthritis and physical therapy
for gait/balance and assistive device/fall prevention.
Social activities may improve socialization and improve cognitive
abilities.1 The patient was scheduled to follow up with primary care
for cardiovascular and generalized health, cancer screening, and
neurology for medications. Fall prevention and surveillance protocols
were also implemented. The patient continued with her antihyper-
tensive medication and calcium/vitamin D with weight-bearing
 A. Lurati / The Journal for Nurse Practitioners xxx (xxxx) xxx
exercises. Weight-bearing exercises may also improve functional ca-
pacity and pain levels. A dietary consult was obtained for weight loss
and heart health. Finally, moist heat therapy and exercise were
implemented for pain and mild osteoarthritis in bilateral hands.
Four months after the initiation of vortioxetine, there was an
improvement of depressive symptoms. The patient and her sons
reported that the patient was experiencing more refreshing sleep
as well as a desire for socialization. She also reported less gener-
alized pain and stated that she “moves around better.” Her PHQ-9
score was an 11 out of 27, and her GAD-7 score was 9 out of 21
(indicating an improvement in depressive and anxiety symptoms)
(Table). Her MMSE and MoCA scores revealed mild improvement
with 20 out of 30 (Table).
In summary, it is challenging to distinguish between symptoms
of apathy and the diagnosis of major depression in patients with
Alzheimer disease. However, in the case of S.D., there was an
improvement in mood, which helped solidify the diagnosis of
major depression.
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Ann Lurati, MPH, DNP, is an acute care nurse practitioner and lecturer at California
State University in Monterey Bay. Dr. Lurati can be reached at alurati@csumb.edu.
In compliance with standard ethical guidelines, the author reports no relationships
with business or industry that may pose a conflict of interest.