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As the average life expectancy of
humans continues to increase so does the risk of developing
Alzheimer’s disease (AD) and other forms of dementia or mild
cognitive impairment (MCI). As people get older, they are also more
likely to suffer falls or injuries that require medical care to
return to function (Shumway-Cook & Woollacott, 2017). With increased
likelihood of physical therapists to have exposure to patients with
complex medical conditions, clinicians must be prepared to recognize
how the intersection of these conditions is likely to affect
treatment and be prepared to adjust accordingly. This article
briefly explores the characteristics of AD as well as how physical
therapists may assist with the prevention and management of
symptoms.
Etiology/Pathophysiology
Although the root cause of AD is not completely understood, the
disease is most notably characterized by the accumulation of a
sticky molecule called Amyloid-Beta Peptide (AB) onto neurons and
vascular structures in the brain. AB is difficult for the body to
remove once it is cleaved from its precursor protein and results in
inflammation triggered by surrounding glial cells. As inflammation
becomes chronic, the induced anaerobic environment in the brain
results in edema and apoptosis in neural structures. Another
characteristic of AD is the buildup of hyperphosphorylated tau
proteins within neurons which result in neurofibrillary tangles
(NFT). These tangles inhibit the transport of nutrients to and from
the soma and ultimately leads to neuronal death (McGough et al.,
2017).
Risk factors, Prevalence, Incidence
AD has several modifiable and nonmodifiable risk factors. As of
2021, there is estimated to be 6.2 million Americans living with AD
who are older than the age of 65 with the prevalence of people with
AD doubles for every 10 years of life from the age of 65 (5.3%
cases) to 85 (34.6% of cases). Women appear to be more susceptible
to the disease than men (61% women, 39% men in 2021) (Alzheimer’
Association, 2021). People with Down Syndrome are reportedly 50%
likely to develop AD as they age because the allele which is
responsible for the production of AB is located on chromosome 21.
The accumulation of BA plaques and neurofibrillary tangles has been
found before the age of 40 in this patient population (NIH, 2020).
Although a small percentage of the cases of AD have familial or
genetic links, there are several modifiable risk-factors that can be
addressed to protect against developing AD or slowing the
progression of the disease including smoking, physical inactivity,
hypertension, obesity, diabetes, and low educational attainment
(McGough et al., 2017).
Signs and Symptoms
People with AD demonstrate signs and symptoms that progressively
interfere with their ability to function independently and
participate in normal daily activities. These include memory loss,
decreased planning- or problem-solving skills, difficulty completing
familiar tasks, confusion, deceased perception of visual and spatial
relationships, word finding in speaking or writing, frequently
misplacing things, decreased judgment, social withdrawal, and mood
and personality changes (Alzheimer’s Association, 2017).
People with dementia are also effected by several motor signs as
well including gait disturbances, extrapyramidal motor impairment,
rigidity, and postural instability. These motor signs all
significantly increase falls risk and decrease ability to
participate in daily activities. Kato-Narita & Radanovic, 2009).
If a patient is demonstrating the hallmark signs and symptoms of
dementia, it is likely that they have lived with the disease for
several years already. Several studies reported detecting biomarkers
of the disease between 13-22 years before the expected onset of
symptoms (Alzheimer’s Association, 2021). An AD diagnosis in
patients older than 65 years old typically results in death 4-8
years later, although its has been reported some individuals living
an additional 20 years (Alzheimer’s Association, 2021).
Screening and Diagnostic Imaging
High risk patients demonstrating signs and symptoms of AD can be
screened for cognitive function using multiple validated tests of
global cognitive function. Two recommended tests are the Mini-Mental
Status Examination (MMSE) and the Montreal Cognitive Assessment
(MoCA). The MMSE can be administered in under 10 minutes and
demonstrates high test-retest and interrater reliability. Baek et
al. (2016) found the MMSE to be useful for discriminating patients
with MCI from those with AD as well as healthy older adults from
those with AD. They also reported a likely ceiling affect of those
with higher educational attainment (Baek et al. 2016). The Montreal
Cognitive Assessment has been tested to demonstrate higher
reliability than the MMSE for detecting mild cognitive decline and
AD. Freitas et al. (2013) determined the sensitivity and specificity
at cut-off scores of 22 for MCI and 17 for AD to be 81%/77% and
88%/98%, respectively. Cut-off scores using the MMSE for were 29 for
MCI and 26 for AD and the sensitivity and specificity was 67%/72%
and 85%/93%, respectively (Freitas et al., 2013). Trzepacz et al.
(2015) further supports the use of the MoCA over the MMSE due to its
inclusion of items measuring executive function, higher-lever
language, and complex visuospatial processing. They also recommend
MoCA in conjunction with other functional tests to detect early MCI
sooner than with the MMSE (Trzepacz et al., 2015). McGough et al.
(2017) reported that motor signs often present years before the
onset of dementia and that slowed gait speed was found to be a
strong predictor of future cognitive decline. This researcher also
supports the suggestion of Trzepacz et al. (2005) by reporting that
the combination of slowed gait and cognitive complaints is a
stronger predictor of cognitive outcomes than either measure on its
own (McGough et al., 2017).
Positron Emission Testing (PET) is a nuclear imaging modality that
can be used to detect both AB and NFTs. A positive test for AB
typically shows deposition in the precuneus, orbitofrontal cortex,
and inferior temporal and posterior cingulate gyrus. Later stage AD
will show additional deposition in the prefrontal, lateral temporal,
and parietal cortices. Although a negative amyloid PET scan can
differentiate other forms of cognitive impairment from AD, a
positive test is not sufficient evidence to establish an AD
diagnosis because many elderly people with normal cognition also
present of elevated AB (Marcus, Mena, & Sybramaniam, 2014). Amyloid
PET scans are typically indicated for people demonstrating symptoms
of early onset AD (<65 years old) or test positive for cognitive
assessment screens with atypical clinical presentation of symptoms.
This imaging modality is considered inappropriate for people over
the age of 65 who meet expected clinical criteria for AD, people
solely with genetic risk factors (presence of APOE-4 gene, Down
Syndrome), and those with cognitive complaints but have not been
confirmed with cognitive screening (Marcus, Mena, & Sybramaniam,
2014).
Treatment and Prevention
Physical therapy intervention for patients, with or without symptoms
of AD should be directed at restoring and/or preserving function and
participation in meaningful activity. As previously mentioned, AD
risk is strongly tied with smoking, physical inactivity,
hypertension, obesity, diabetes, and low educational attainment
(McGough et al. 2017). With appropriate patient education and
maintenance of a regular exercise program, physical therapists can
help manage or eliminate many modifiable risk factors to preserve
physical and cognitive function and possibly even delay the onset of
AD symptoms.
Regular exercise provides abundance of protective mechanisms against
the neurodegenerative processes observed in the onset of AD. Aerobic
exercise is attributed to increased levels of Brain-Derived
Neurotropic Factor (BDNF), which is a neurotransmitter in the brain
that aids with glucose control and provides neuroprotective
properties. Aerobic exercise also increases neurogenesis in the
hippocampus which may preserve and/or improve memory and learning.
Resistance training increase levels of insulin-like growth factor 1
(IGF-1) which inhibits apoptosis and aids in maintaining
neuroplasticity. Other benefits of regular exercise including
increased cerebral blood flow, increased vascular health and
compliance, reduced mean arterial blood pressure, and decreased
systemic inflammation directly and indirectly aid in AD prevention
and/or delay of symptoms by managing potential modifiable risk
factors (McGough et al., 2017). These benefits have been observed in
patients following exercise programs consistent with recommendations
made by the American College of Sports Medicine and American Heart
Association: 150 minutes of moderate-intensity or 75 minutes
vigorous intensity aerobic exercise weekly in addition to
strengthening exercises performed twice weekly (McGrough et al.,
2017).
People with AD become a significant falls risk over time due the
progressive onset of motor symptoms, visuospatial decline, decreased
judgement, and muscular atrophy due to decreased activity (McGrough
et al., 2017). Kato-Narita & Radanovic (2009) found that 80% of
patients with AD, despite stage of condition, experienced falls
within their own homes. Most of these falls (43.1%) were due to
environmental hazards followed by instability (22.6%) and dizziness
(11.3%). More than 1 in 5 falls were considered “ignored” due to
lack of patient recall and absence of caregiver (Kato-Narita &
Radanovic, 2009). In attempt to improve or delay falls risk status,
physical therapy intervention can be aimed at reducing falls risk
through dual-task based training to improve gait, balance, and
postural control. In a retrospective analysis, Longhurst et al.
(2020) found treatment sessions that incorporated dual tasking into
aerobic activity (20-25 minutes), strengthening (15-20 minutes), and
balance training (15-20 minutes) significantly improved AD patient
outcomes beyond the MCID and MDC for MoCa, 6-Minute Walk Test, Mini
Balance Evaluation Systems Test, and Five Times Sit-to-Stand test.
Roughly 75% patients with AD and 80% of patients with MCI improved
in at least one outcome measure for gait, balance, or cognition
(Longhurst et al., 2020). This research suggests dual-task training
in conjunction with aerobic exercise, strength training, and balance
training may be more effective at preserving cognitive and physical
function for patients with AD prior to or in the early in the onset
of symptoms.
Conclusion
AD is a neurodegenerative disease that primarily effects the elderly
causing progressive decline physically, socially, and cognitively.
Once an AD diagnosis is established, symptoms typically become fatal
within 10 years, with the much of the time being spent in the care
of nursing staff. Because the disease usually progresses silently
for several years before the onset of symptoms, clinicians should
seek to eliminate modifiable risk factors in all patients,
especially those 65 years of age and older. By providing education
about the importance of eliminating risk factors and helping
patients adhere to a regular exercise program, physical therapists
can allow patients to have greater opportunity and independence with
participating in activities that are meaningful to them for a longer
period of time.
Last revised: 12/22/21
by David Carrubba, SPT
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