PharmD Program / Fourth Year

Disorder Block XV Neurological and psychological

ALZHEIMER’S & DEMENTIA

DISEASE
TBL

PharmD Faculty of Pharmacy/ Libyan International Medical University

 Intended learning outcomes
2

By the end of this session you will be able to:

 Discuss pathogenesis of Alzheimer’s disease.
 Outline the epidemiological features of dementia.
 Explain the impact of dementia on quality of life.
 Discuss the quality of life assessment method for a patient with
dementia.
 Identify the adverse effects of drugs used to treat Alzheimer’s
disease and/or dementia.
 Explain the primary treatment goals of therapies for Dementia /
Alzheimer’s. Describe the general approach to nonpharmacologic
strategies for managing behavioral symptoms in patients with
Dementia / Alzheimer’s.
 Intended learning outcomes
3

 Discuss the source, nature, and medicinal uses of the active

constituents of Ginkgo biloba and Melissa officinalis.
 Discuss the role of acupuncture in the management of Alzheimer’s
disease.
 Explain family-based care tips for a patient with dementia.
 Alzheimer’s disease
4

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 Pathogenesis of Alzheimer’s disease
5

The fundamental abnormality in AD is the accumulation

of two proteins (Aβ and tau) in specific brain regions, In the forms of plaques and
tangles, respectively; these changes result in secondary effects including neuronal
dysfunction, neuronal death, and inflammatory reactions

Plaques are deposits of aggregated Aβ peptides in the neuropil, while tangles are
aggregates of the microtubule binding protein tau, which develop intracellularly
and then persist extracellularly after neuronal death.

Both plaques and tangles appear to contribute to neural dysfunction.

The details of the interplay between the processes that lead to the accumulation of
these abnormal aggregates are a critical aspect of AD pathogenesis that has yet
to be unraveled

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Clinical and
experimental
evidence strongly
suggests
that Aβ generation
is the critical
initiating event for
the development of
AD.
 Pathogenesis of Alzheimer’s disease
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 Pathogenesis of Alzheimer’s disease
8

The amyloid plaques build up outside of the nerve cells [in the brain] and now we
know that when the nerve cells interact with the plaque, it causes the nerve cell to
make a tangle inside,” explains Rudy Tanzi, Ph.D., director of the Alzheimer’s
Genome Project

“And that tangle then chokes the nerve cell from within and kills it. So the killing
process begins with the amyloid- that’s kind of the gun-but the tangle is the bullet.”

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 Pathogenesis of Alzheimer’s disease
9

Role of inflammation. Both genetic and histologic studies have indicated that the innate immune
system responds to Aβ and tau.
Deposits of Aβ elicit an inflammatory response from microglia and astrocytes. This response
probably assists in the clearance of the aggregated peptide, but also may stimulate the
secretion of mediators that cause neuronal injury over time 13/11/2023
 Pathogenesis of Alzheimer’s disease
10

Further research, particularly in the genetic domain, led to

identification of APP and Presenilin genes (APP, PSEN1, and PSEN2) and mutations
in these genes as cause of rare forms of
early-onset familial AD.
• On other hand, ε4 allele of apolipoprotein E gene (APOE) has been
recognized as a major risk factor for late-onset AD.

However, there is growing evidence for the role of additional factors such as
oxidative stress, neuroinflammation, and mitochondria dysfunction in the
pathogenesis of AD.

Basis for cognitive impairment: The presence of a large burden of plaques and
tangles is strongly associated with severe cognitive dysfunction

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 The epidemiological features of dementia
11
 Dementia, a syndrome with many causes, is defined as an acquired deterioration in
cognitive abilities that impairs the successful performance of activities of daily living.
 The number of people living with dementia worldwide in 2015 was estimated at 47.47
million, reaching 75.63 million in 2030 & 135.46 million in 2050.
 When age-standardised to a standard western European population, the prevalence for
East Asia increased from 4.98 - 6.99% & in the sub-Saharan African regions from a
range of 2.07 - 4.0%, to 4.76%.
 It affects >5 million people in the United States & results in a total annual health care
cost between $157 and $215 billion.
 The incidence of dementia doubled with every 5.9 year increase in age, from 3.1/1000
person years at age 60-64, to 175.0/ 1000 person years at age 95+.
 While the incidence of dementia appeared to be higher in countries with high-incomes
than in low- or middle-income countries, this was largely an artefact, due to the specific
diagnostic criteria used.
 Episodic memory, the ability to recall events specific in time & place, is the cognitive
function most commonly lost; 10% of persons age >70 years & 20–40% of individuals
age >85 years have clinically identifiable memory loss
 Alzheimer’s disease is the most common cause of dementia (60–80% of all cases). 13/11/2023
12
 Worldwide 7.7 million new cases of dementia were anticipated each year, implying
one new case every 4.1 seconds. This means that there were 3.6 million (46%) new
cases per year in Asia, 2.3 million (31%) in Europe, 1.2 million (16%) in the
Americas & 0.5 million (7%) in Africa

..

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 The impact of dementia on quality of life
13
 Dementia & cognitive impairment are the leading chronic disease contributors to
disability particularly, dependence among older people worldwide.
While older people can often cope well & remain reasonably independent even
with marked physical disability, the onset of cognitive impairment quickly
compromises their ability to carry out complex, but essential tasks in daily life.
 People living with dementia will increasingly have difficulty to meet their basic
personal care needs.
 Older people frequently have multiple health conditions such as chronic physical
diseases coexisting with mental or cognitive disorders, the effects of which may
combine together in complex ways leading to disability & needs for care. However,
cognitive impairment & dementia make the largest contribution to needs for care,
much more than other types of impairment & other chronic diseases.
 The strain of the caregivers (hours spent caregiving detracting from other
activities, particularly leisure & socializing), psychological (emotional strain, leading
to a high prevalence of anxiety & depression) & economic (increased costs, coupled
with giving up or cutting back on work to care).
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 The quality of life assessment method for a
patient with dementia.
14
 Two large categories of tools stand out: generic versus specific instruments.
 In dementia, the specific modality is privileged because it takes the pathology’s
characteristics into account, lends itself to a more precise evaluation regarding the
person’s life experience & is more robust psychometrically
 Depending on who is doing the evaluation, it is possible to distinguish:
(1) Self-rated tools (usual procedure in a non-pathological context), which can be
used for patients who are in early or moderate stages of dementia & even for some
patients who have severe dementia
(2) Proxy (formal or informal caregiver)-rated tools
 (3) Tools that use both methods.
 The literature distinguishes methods of direct observation (primarily useful in an
institutional setting) versus questionnaires.

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AAIQoL: Activity and Affect Indicators of Quality of Life; CDQLP: Community Dementia Quality of Life Profile; QoL-AD: Quality of Life in
Alzheimer’s Disease; D-QoL: Dementia Quality of Life Instrument; ADRQL: Alzheimer’s Disease-Related Quality of Life instrument; QUALID:
Quality of Life in Late-Stage Dementia; QOLAS: Quality ofLife Assessment schedule; DCM: Dementia Care Mapping; CBS: Cornell-Brown Scale for
Quality of Life in Dementia; QoL-D: Quality of Life in (for) Dementia scale; QLDJ: Quality of Life instrument for the Japanese elderly with
Dementia; The Vienna List; DEMQOL; BASQID: Bath Assessment of Subjective Quality of Life in Dementia; QUALIDEM; OQOLD(A): Observing
QOL in Dementia (for Dementia Advanced); DQI: Dementia Quality of life Instrument; and DEMQOL-(Proxy-)U
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QoL definitions specific to dementia except WHOQOL:
 in Quality of Life in (for) Dementia scale (QoL-D), QoL in dementia as “the
integration of cognitive functioning, Activities of Daily Living (ADL), social
interactions & psychological well-being.” This definition refines that more general
one: “QoL is a multidimensional concept encompassing (at least) social,
psychological & physical domains (both subjective & objective).
 In The Cornell-Brown Scale for Quality of Life in Dementia (CBS), “high QoL
typically is indicated by presence of positive affect, physical & psychological
satisfactions, self-esteem & a relative absence of negative affect & experiences.”
 For Quality of Life instrument for the Japanese elderly with Dementia (QLDJ), QoL
of people with dementia is “a condition in which an elderly person with dementia
enjoys daily life with lively interactions with the surroundings based upon the sense
of self that has been cultivated during entire life course.” In this, an instrument was
add the necessity to experience a minimum of aggressive/negative behaviours.
 QUALIDEM define dementia-specific QoL as “the multi-dimensional evaluation of
the person–environment system of the individual, in terms of adaptation to the
perceived consequences of the dementia 13/11/2023
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 According to Lawton, QoL is “a multidimensional construct that should include not
only objective (observable) indices of well-being judged against socio-normative
criteria, but also the individual’s own subjective perception of his position in life.”
 In the Activity and Affect Indicators of Quality of Life (AAIQoL), “a high QoL level
was defined in terms of high positive affect & high activity,” reflecting the equal
weight given to both a subjective indicator (affect) & a more objective indicator
(activity).
 For the Quality of Life in Late-Stage Dementia (QUALID), “a good QoL is favoured
by an engagement (& the comfort) in a small number of familiar, highly repetitive &
very basic activities of life, considered as important by social norms (e.g. eating &
engaging & interacting with others)”
 The combination of a subjective indicator (well-being) & an objective indicator
(activity–behavioural category) in the direct observational tools DCM and OQOLD
(A) gives an estimation of the quality of care provided in institution for people with
dementia, which constitutes a major component to their QoL.

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The adverse effects of drugs used to treat
19
Alzheimer’s disease and/or dementia

 Bradycardia.
 Excessive secretions.
 Bronchoconstriction.
 Gastrointestinal hypermotility ( diarrhea).
 Neuromuscular action causes muscle fasciculation and
increased twitch tension, and can produce muscle
weakness

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The adverse effects of drugs used to treat
Alzheimer’s disease and/or dementia
20

More common s.e (Memantine:

 Dizziness, drowsiness.
Confusion,

Headache except malignant anemia
.
Serious side effects:
 Allergy.

 Hepatitis.

 Pancreatitis.

 Change in mental health ( Agitation, hallucinations,

thoughts of suicide).
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 Treatment Goals for Dementia / Alzheimer’s

Primary goals include

in case application written
1. Focused on delaying disease progression. (Alzheimer’s)
2. Preservation of functioning as long as possible. (Alzheimer’s)
Secondary goals include
1. Treating psychiatric and behavioral symptoms that may occur during
the course of the disease.( Alzheimer’s)
2. Maintain quality of life. (Dementia / Alzheimer’s)
3. Maximize function in daily activities. (Dementia / Alzheimer’s)
4. Enhance cognition, mood and behavior. (Dementia / Alzheimer’s)
5. Foster a safe environment. (Dementia / Alzheimer’s)
6.21 Promote social engagement, as appropriate. (Dementia / Alzheimer’s)
 Non-pharmacologic strategies for managing
behavioral symptoms in patients with Dementia

Non-pharmacologic options recommended as first-line treatments,

in parallel with pharmacologic or other treatment options.
Non-pharmacologic treatments may include a general approach
(caregiver education and training in problem solving,
communication and task simplification skills, patient exercise,
and/or activity programs), or a targeted approach in which
precipitating conditions of a specific behavior are identified and
modified (eg, implementing nighttime routines to address sleep
disturbances). Using the case of Mr A, which characterize common
behavioral symptoms of dementia and describe an assessment
strategy for selecting evidence-based non-pharmacologic
22treatments. 13/11/2023
 The link for Potential Non-pharmacologic Strategies to Manage Mr. A′s
Targeted Behaviors

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711645/table/T1/?report=objectonly

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 Ginkgo biloba
25

Ginkgo biloba is one of the longest living tree species in the world. Ginkgo trees can live as
long as a thousand years.

The leaves and roots are contains the active constituent:

EGb 761 (extract of Ginkgo biloba 761) it contains:

24% flavonoid and 6% terpenes (ginkgolides and bilobalide).

• Uses:

 The extract of ginkgo biloba (EGb 761) was clinically effective in treating Alzheimer's
dementia. It is also safe to use and possibly effective in stabilizing and possibly improving
cognitive and the social functioning patients with Alzheimer.

 ginkgo also improves cognitive function because it promotes good blood circulation in
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the brain and protects the brain and other parts from neuronal damage.
 Melissa officinalis
26

Melissa officinalis is a plant cultivated in some parts of Iran. The leaves are
used in folk medicine.
The leaves contains Rosmarinic acid and volatile oil (citral and citronella).
• Uses:
 Rosmarinic acid have potent antiviral properties that may aid in the
treatment of certain viral infections.
 Citral in the plant extract inhibit cholinesterase (an enzyme) targeted by
the drugs used to treat Alzheimer's disease.
 Citral and citronella is strongly antispasmodic and aids in calming
nerves, relieving menstrual cramps and insomnia.
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 The role of acupuncture in the
management of Alzheimer’s disease
27

 It is a safe treatment modality for Alzheimer disease

patients.
 Acupuncture improves drug effectiveness for the
treatment of Alzheimer disease.
 acupuncture plus the drug is more effective than
using only the drug as a standalone treatment.

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 Family-based care tips for a patient with
dementia
28
Family caregivers are vital to ensure the health & quality of life of a patient with
dementia. The caregiving process is complex & challenging.
Not all of the strategies will apply to all family, as each caregiver & family is unique.
These strategies include:
 Know the basic information concerning the care of patient with dementia: What
are the current needs for feeding & hygiene? Medication? Legal & financial
matters? What is the best way to communicate? To deal with behavioural issues?
How will the disease progress?
 Don’t go it alone! Caring for patient with dementia is often a 24/7 job with
constantly changing (& increasing) responsibilities & primary caregivers are at risk
for depression & declining health themselves. Say “yes” to offers of help, even for
small things like running errands or providing a meal. Make arrangements for
getting a break – whether it’s just to get away for a few hours or for a short
vacation. Accept help from family members or contact community agencies that
can make recommendations for respite care.

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 Keep the patient active, to the extent that it is physically possible. Physical activity
can decrease anxiety & boredom & can improve sleep. Walking & gentle exercise
will also strengthen the leg muscles & help prevent falls.
 Foster connections: As dementia progresses, the patient increasingly loses a sense
of self and of his or her place in the world. Short-term memory often declines in
the early stages of dementia, while, long memories may be intact. One way to
foster connections is to revive those memories: Look through family photo albums,
play or sing old songs, read a favourite book out loud, watch an old movie.
 Foster a connection with animals: Studies have shown that animals have an
instinctive ability to help in healing & that a connection with animals can help
reduce stress, improve confidence & enhance overall well-being for those affected
by early-stage dementia.
 Set a positive mood for interaction. The attitude & body language communicate
feelings & thoughts more strongly than words do. Set a positive mood by speaking
in a pleasant & respectful manner. Use facial expressions, tone of voice & physical
touch to help convey messages & show feelings of affection.
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 Get the person’s attention. Limit distractions & noise—turn off the radio or TV,
close the curtains or shut the door, or move to quieter surroundings. Before
speaking, make sure you have his/her attention; address his/her by name, identify
yourself by name & relation & use nonverbal cues & touch to help keep his/her
focused. If he/she is seated, get down to her level & maintain eye contact.
 State a message clearly. Use simple words & sentences. Speak slowly, distinctly & in
a reassuring tone. Refrain from raising voice higher or louder; instead, pitch voice
lower. If he/she doesn’t understand the first time, use the same wording to repeat a
message or question. If he/she still doesn’t understand, wait a few minutes &
rephrase the question. Use the names of people & places instead of pronouns (he,
she, they) or abbreviations
 Ask simple, answerable questions. Ask one question at a time; those with yes or no
answers work best. Refrain from asking open-ended questions or giving too many
choices. For example, ask, “Would you like to wear your white shirt or your blue
shirt?” Better still, show her the choices—visual prompts & cues also help clarify a
question & can guide his/her response.
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 Listen with your ears, eyes, and heart. Be patient in waiting a reply. If he/she is
struggling for an answer, it’s okay to suggest words. Watch for nonverbal cues &
body language & respond appropriately. Always strive to listen for the meaning &
feelings that underlie the words.
 Break down activities into a series of steps. This makes many tasks much more
manageable. You can encourage him/her to do what he can, gently remind him/her
of steps he/she tends to forget & assist with steps he/she’s no longer able to
accomplish on his/her own. Using visual cues, such as showing him with your hand
where to place the dinner plate, can be very helpful.
 When the going gets tough, distract and redirect. If he/she becomes upset or
agitated, try changing the subject or the environment. For example, ask him/her
for help or suggest going for a walk. It is important to connect with the person on a
feeling level, before you redirect. You might say, “I see you’re feeling sad—I’m sorry
you’re upset. Let’s go get something to eat.”

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 Respond with affection and reassurance. People with dementia often feel
confused, anxious & unsure of themselves. Further, they often get reality confused
& may recall things that never really occurred. Avoid trying to convince them they
are wrong. Stay focused on the feelings they are demonstrating (which are real) &
respond with verbal & physical expressions of comfort, support & reassurance.
Sometimes holding hands, touching, hugging & praise will get the person to
respond when all else fails.
 Remember the good old days. Remembering the past is often a soothing &
affirming activity. Many people with dementia may not remember what happened
45 minutes ago, but they can clearly recall their lives 45 years earlier. Therefore,
avoid asking questions that rely on short-term memory, such as asking the person
what they had for lunch. Instead, try asking general questions about the person’s
distant past—this information is more likely to be retained.
 Maintain your sense of humor. Use humor whenever possible, though not at the
person's expense. People with dementia tend to retain their social skills and are
usually delighted to laugh along with you.
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 The End

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