Understanding and Diagnosing Dementia

Understanding & Diagnosing
Dementia
By Kimmer Collison-Ris
MSN, FNP-BC, WOCN, MS CAM

DEMENTIA DEFINED
“The term dementia is used to define
a heterogeneous group of progressive
and degenerative brain pathologies,
clinically characterized by
deterioration in memory, learning,
orientation, language,
comprehension, and judgment.”

Risk Factors
Abstract
• Background: Late-life depression may increase the risk of incident dementia, in
particular of Alzheimer’s disease and vascular dementia.
• Aims: To conduct a systematic review and meta-analysis to evaluate the risk of
incident all-cause dementia, Alzheimer’s disease and vascular dementia in
individuals with late-life depression in population-based prospective studies.
• Method: A total of 23 studies were included in the meta-analysis. We used the
generic inverse variance method with a random-effects model to calculate the
pooled risk of dementia, Alzheimer’s disease and vascular dementia in older adults
with late-life depression.
• Results: Late-life depression was associated with a significant risk of all-cause
dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer’s disease (1.65, 95% CI
1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001).
Subgroup analysis, based on five studies, showed that the risk of vascular
dementia was significantly higher than for Alzheimer’s disease (P = 0.03).
• Conclusions: Late-life depression is associated with an increased risk for all-cause
dementia, vascular dementia and Alzheimer’s disease. The present results suggest
that it will be valuable to design clinical trials to investigate the effect of late-life
depression prevention on risk of dementia, in particular vascular dementia and
Alzheimer’s disease.
• Breno S. Diniz, Meryl A. Butters, Steven M. Albert, Mary Amanda Dew, Charles F. Reynolds (2013).
Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and
meta-analysis of community-based cohort studies. The British Journal of Psychiatry May 2013, 202
(5) 329-335; DOI: 10.1192/bjp.bp.112.118307

https://www.kindlycare.com/dementia-definition/

Causes of Dementia
• Chronic infections
• Drugs & toxin buildup
• Degenerative
• Endocrine & Metabolic
disturbances
• Psychiatric
• Trauma & diffuse brain
damage
• Vitamin Deficiencies
• Miscellaneous

Dementia Types
Type Description
Cortical Dementia Brain damage mainly impacts the brain’s cortex (outer layer). Tends
to cause problems w/language, memory, social behavior, and
thinking.
Subcortical Dementia Impacts parts of the brain below the cortex. It causes changes in
emotions and movements as well as problems with memory.
Progressive Dementia Dementia that worsens over time, slowly interfering with increasing
cognitive impairments and abilities.
Primary Dementia Dementia from Alzheimer’s that is not caused by any other disease.
Secondary Dementia Occurs as a result of physical disease or injury.

Dementia Types
Abstract
• Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have
Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most
common pathologic subgroup after pure Alzheimer's disease (AD).The Consortium on Dementia
with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with
Lewy bodies (DLB) and to establish a common framework for the assessment and characterization
of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes
a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with
neuroleptic medication, and the possibility that DLB patients may be particularly responsive to
cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to
dementia as the central feature of DLB. Attentional impairments and disproportionate problem
solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function,
persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are
core features with diagnostic significance in discriminating DLB from AD and other dementias.
Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical
LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-
related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified
optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB
frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be
classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a
simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer
pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical
neurofibrillary tangles being much less common. The precise nosological relationship between DLB
and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who
subsequently develop neuropsychiatric features. Finally, we recommend procedures for the
selective sampling and storage of frozen tissue for a variety of neurochemical assays, which
together with developments in molecular genetics, should assist future refinements of diagnosis
and classification.

Assessing for Dementia
Abstract
• Article abstract-The Neuropsychiatric Inventory (NPI) was developed to assess
psychopathology in dementia patients. It evaluates 12 neuropsychiatric
disturbances common in dementia: delusions, hallucinations, agitation, dysphoria,
anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-
time behavior disturbances, and appetite and eating abnormalities. The severity
and frequency of each neuropsychiatric symptom are rated on the basis of scripted
questions administered to the patient's caregiver. The NPI also assesses the
amount of caregiver distress engendered by each of the neuropsychiatric
disorders. A total NPI score and a total caregiver distress score are calculated, in
addition to the scores for the individual symptom domains. Content validity,
concurrent validity, inter-rater reliability, and test-retest reliability of the NPI are
established. Different neurologic disorders have characteristic neuropsychiatric
manifestations and distinctive NPI profiles. The NPI is sensitive to treatment effects
and has demonstrated the amelioration of behavioral symptoms in Alzheimer's
disease by cholinergic agents. The NPI is a useful instrument for characterizing the
psychopathology of dementia syndromes, investigating the neurobiology of brain
disorders with neuropsychiatric manifestations, distinguishing among different
dementia syndromes, and assessing the efficacy of treatment.
• Jeffrey L. Cummings (1997). The Neuropsychiatric Inventory. Neurology May 1997, 48 (5 Suppl 6) 10S-
16S; DOI: 10.1212/WNL.48.5_Suppl_6.10S. Retrieved from
http://n.neurology.org/content/48/5_Suppl_6/10S.short.

Neurobiology of Dementias
Abstract:
• Purpose of review Neuropsychiatric disturbances in dementia are prevalent, and research is
uncovering their neurobiological correlates.
• Recent findings Late-onset depression appears to be associated with Alzheimer's disease
pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease
pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for
both late-onset depression and Alzheimer's disease and may partly mediate their
relationship. Monoamine changes are robust finding in Alzheimer's disease and may account
for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to
be increased by several genes also implicated in schizophrenia (e.g., catechol-O-
methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be
related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian
sleep–wake cycles, including decreased night-time melatonin. Sleep apnea may be related to
apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement
sleep behavior disorder is intricately related to synucleinopathies, such as dementia with
Lewy bodies, but synuclein changes may not totally explain this relationship.
• Summary Neuropsychiatric disturbances are a core feature of dementia and worsen many
clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep
disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies
increasingly provide insight into the origins of these psychiatric symptoms in dementia.
• Meeks TW, Ropacki SA, and Jeste DV (2006). The neurobiology of neuropsychiatric syndromes
in dementia. Current Opinion in Psychiatry. Nov 2006, Vol 19, Issue 6, pp 581-586. doi:
10.1097/01.yco.0000245746.45384.0e http://journals.lww.com/co-
psychiatry/Abstract/2006/11000/The_neurobiology_of_neuropsychiatric_syndromes_in.7.aspx

Vascular Dementia
Abstract
• Vascular dementia is the most common cause of dementia in the elderly after
Alzheimer's disease. Many forms of vascular dementia have been described: multi-
infarct dementia, lacunar dementia, Binswanger's subcortical encephalopathy,
cerebral amyloid angiopathy, white matter lesions associated with dementias,
single infarct dementia, dementia linked to hypoperfusion and haemorrhagic
dementia. The difficulty of diagnosing vascular dementia must not be
underestimated and an international consensus is needed for epidemiological
studies. The NINCDS-AIREN group has recently published diagnostic criteria. The
State of California Alzheimer's Disease Diagnostic and Treatment Centers also
proposed some which differ from the NINCDS-AIREN criteria in considering only
ischaemic vascular dementia and not other mechanisms such as haemorrhagic or
hypoxic lesions. Most studies stress hypertension as the most powerful risk factor
for all forms of vascular dementia. The incidence rate ranges from 7 per 1000
person-years in normal volunteers to 16 per 1000 person-years in hypertensive
patients. No therapeutic attempt has influenced the course of the disease once
the dementing condition is established. The only effective approach is preventive
treatment. The objective of the SYST-EUR Vascular Dementia project is to confirm
that the treatment of isolated systolic hypertension is able to reduce its incidence.
– F. Forette , A-S. Rigaud , M. Morin, M. Gisselbrecht, P. Bert (1995). Assessing vascular
dementia.The Netherlands Journal of Medicine Volume 47, Issue 4, October 1995, Pages 185-
194

Early Onset Dementia
Abstract
• Early-onset familial Alzheimer's disease (EOFAD) is a condition
characterized by early onset dementia (age at onset < 65 years) and a
positive family history for dementia. To date, 230 mutations in presenilin
(PS1, PS2) and amyloid precursor protein (APP) genes have been identified
in EOFAD. The mutations within these three genes (PS1/PS2/APP) affect a
common pathogenic pathway in APP synthesis and proteolysis, which lead
to excessive production of amyloid β. Compared with sporadic Alzheimer's
disease (AD), EOFAD has some distinctive features including early age at
onset, positive familial history, a variety of non-cognitive neurological
symptoms and signs, and a more aggressive course. There is marked
phenotypic heterogeneity among different mutations of EOFAD. Studies in
presymptomatic mutation carriers reveal biomarkers abnormalities.
EOFAD diagnosis is based on clinical and family history, neurological
symptoms and examination, biomarker features, as well as genotyping in
some cases. New therapeutic agents targeting amyloid formation may
benefit EOFAD individuals.
– Wu L, Rosa-Neto P, Hsiung, G-Y R, and Sadovnick AD (2012). Early-Onset
Familial Alzheimer’s Disease (EOFAD). Canadian Journal of Neurological
Sciences. Vol 39, Iss445.ue 4, July 2012, pp 436-445.

www.slideshare.net-
Frontotemporal Dementias (FTD)
• Comprises 5-10% diagnosed w/Dementia
• Affects 75% younger individuals ( ages 45-65 years)
• Different forms of FTD
– Behavioral: causes changes in personality, social behavior, loss of
insight, and apathy
– Primary progressive aphasia: language impairment initially, eventually
other cognitive domains affected
– Motor neuron diseases with FTD component (ALS)
• There are no approved treatments
– Meds are used to treat behaviors

nurse-practitioners-and-physician-assistants.advanceweb.com-

Assessing for Dementia
Abstract
• Accurate clinical staging of dementia in older subjects has
not previously been achieved despite the use of such
methods as psychometric testing, behavioural rating, and
various combinations of simpler psychometric and
behavioural evaluations. The Clinical Dementia Rating
(CRD), a global rating device, was developed for a
prospective study of mild senile dementia--Alzheimer type
(SDAT). Reliability, validity, and correlational data are
discussed. The CRD was found to distinguish
unambiguously among older subjects with a wide range of
cognitive function, from healthy to severely impaired.

“Test Your Memory” screen
• The Test Your Memory [Brown et al. 2009] test was a
recently developed 10-item cognitive test designed to be
self-administered under medical supervision.
• The maximum score is 50; at a score of 30 or below, the
test has good specificity and sensitivity [comparable to
MMSE and Addenbrookes Cognitive Assessment –
Revised (ACE-R)] in distinguishing dementia from
nondementia cases [Hancock and Larner, 2011].
• This form of test may be attractive for time-limited
clinicians wanting to screen for dementia, especially in
primary care.

Mini-Mental State Examination
• The MMSE [Folstein et al. 1975] is by some way the best known and
most widely used measure of cognition in clinical practice
worldwide. This scale can be easily administered by clinicians or
researchers with minimal training, takes around 10 min and
assesses cognitive function in the areas of orientation, memory,
attention and calculation, language and visual construction. Patients
score between 0 and 30 points, and cutoffs of 23/24 have typically
been used to show significant cognitive impairment. It is widely
translated and used. A standardized version [Molloy et al. 1991]
improves its reliability, and is probably most important for research
settings. The MMSE is unfortunately sometimes misunderstood as a
diagnostic test, when it is in fact a screening test with relatively
modest sensitivity. It has floor and ceiling effects and limited
sensitivity to change. This in theory should limit its wider use in
detecting change in clinical work and in research studies, though in
these contexts it is still widely used, and even advocated [NICE,
2006].

Mini-Cog
• The Mini-Cog [Borson et al. 2000] is a very short test
(3 min) suitable for primary care screening for
dementia. It incorporates the clock-drawing test,
adding a three-item delayed word recall task. It
showed comparable sensitivity and specificity to the
Mini-Mental State Examination (MMSE) in classifying
community cases of dementia [Borson et al. 2003].

MoCa-B Assessment Tool
• The MoCA is a helpful screening test for persons who score above
the cut-off on the MMSE and for a well-educated person who
complains only of memory impairment. The 30-point test can be
administered in approximately 10 min, and the test protocols,
administration instructions, and normative data are freely
available for clinicians on the MoCA website (www.mocatest.org).
Cognitive functions tested include attention and working
memory, short-term memory recall, visuospatial abilities,
language abilities, and executive functions such as divided
attention, semantic fluency, and abstraction. Considerations for
the MoCAs use in special populations such as with the visually
impaired [19] and individuals with low levels of education have
also been developed and validated.
– https://www.sciencedirect.com/topics/neuroscience/montreal-cognitive-assessment

Clock drawing Test
• Many versions of the clock-drawing test have been
created, with multiple scoring algorithms [Brodaty
and Moore, 1997].
• Patients are often asked to draw a clock face with
numbers and hands (indicating a dictated time).
• The design is a quick and acceptable screening test
for dementia as it is fast, requiring no training and
scoring methods are simple. It demonstrates good
sensitivity and specificity as a screening test.
However, it assesses only a very narrow part of
cognitive dysfunction seen in dementia, and many
other conditions (e.g. stroke) will affect it directly.

General Practitioner assessment of Cognition
• The General Practitioner assessment of Cognition
(GPCOG) [Brodaty et al. 2002] was designed for use
in primary care and includes nine direct patient
cognitive items, and six informant questions
assessing change over several years. In total, it takes
about 6 min. It has strong performance on sensitivity
and specificity versus MMSE in detecting dementia in
a typical primary care population [Ismail et al. 2009].

Neuropsychiatric Inventory
• The Neuropsychiatric Inventory [Cummings et al. 1994]
assesses a wide range of behaviours seen in dementia for
both frequency and severity. These include delusions,
agitation, depression, irritability and apathy. The scale takes
10 min for a clinician to administer to a carer. It has good
psychometric properties and is widely used in drug trials,
while being short enough (especially with patients without a
wide range of behavioural issues) to consider for use in clinical
practice.

6-CIT
• The 6-CIT [Brooke and Bullock, 1999] was
designed for screening in a primary care
setting. It takes 3–4 min to administer, and
scoring is between 0 and 28, with cutoffs of
7/8 showing good screening sensitivity and
specificity. It is easy to administer, though
scoring is less intuitive than AMTS.

The Geriatric Depression Scale
• The Geriatric Depression Scale (GDS) [Yesavage et al.
1983] is the most commonly used assessment of
depressed mood among older people, and has been
shortened to numerous versions, including a popular
15-item version (GDS-15) [Sheikh and Yesavage, 1986].
GDS-15 is usually self rated though can be rated by an
assessor. It is sensitive to change and is reliable in older
people in institutional care. It takes about 5–10 min to
administer. Its major drawback in dementia is that it
has been validated for people with mild dementia, but
not for those with moderate to severe dementia
(among whom completion rates may be low due to
difficulty comprehending questions).

Diagnosing AD
Abstract
• Alzheimer’s disease (AD) is a chronic neurodegenerative disorder and the most
common cause of dementia. It is one of the principal causes of disability and
decreased quality of life among older adults. Progress in our clinical knowledge of
AD has led to more reliable diagnostic criteria and accuracy, and research efforts
are expanding to uncover the earliest manifestations and even the
presymptomatic phases of the disease. The diagnosis of AD is primarily one of
inclusion and usually can be made using standardized clinical criteria. There is
currently no cure for AD. Current treatment focuses on establishing an early
accurate clinical diagnosis, early institution of cholinesterase inhibitors and/or N-
methyl-d-aspartate (NMDA) receptor–targeted therapy. Treating medical
comorbidities and dementia-related complications, ensuring that appropriate
services are provided, addressing the long-term well-being of caregivers, and
treating behavioral and psychological symptoms with appropriate
nonpharmacologic and pharmacologic interventions also are important. The
initiating and propagating pathologic processes and the anatomic location of the
earliest changes will become new targets of research and therapeutic
development. A possible precursor of AD, mild cognitive impairment (MCI), is
under investigation as a possible therapeutic starting point for disease-modifying
interventions. This article provides a research update of current understanding in
the diagnosis and treatment of AD and in emerging areas of interest such as MCI,
detection of AD in the predementia phase, and neuroimaging in AD.
– Desai AK and Grossberg GT (2005). Diagnosis and Treatment of Alzheimer’s Disease.
Neurology June 28, 2005, 64; https://doi.org/10.1212/WNL.64.12_suppl_3.S34 .

www.my-dementia.co.uk-
Comparing Memory Symptoms

Pharmacotherapy for Dementia
• Efforts to find effective drug therapy for
dementia have frustrated scientists. Many
drugs used for dementia are limited by side
effects, short duration of action, and the need
for frequent monitoring of blood levels or
other laboratory values to prevent toxicity.
• https://www.emedicinehealth.com/dementia_medicati
on_overview/article_em.htm

Pharmacotherapy…
• treatment is involves addressing symptoms of
dementia, and improving co-occurring
behavioral manifestations
– Anxiety
– Psychosis
– Depression
– Sleep disturbances
– Mood swings
– Disordered eating behaviors
– and assessing quality of other interventions

Acetylcholinesterase inhibitors
• Acetylcholinesterase (AChE) inhibitors are approved by the
United States Food and Drug Administration (FDA) for
treatment of Alzheimer disease
• Function:
– delay the breakdown of acetylcholine (brain chemical needed required
for nerve cells communication.
– Might be useful for mild-to-moderate AD.
– Once AChE inhibitors initiated must be used indefinitely.
• Cessation may cause an abrupt, possibly severe, cognitive and behavioral
decline which is often unresolved by restarting AChE inhibitor.
• cause for this significant decline with cessation is unknown
– improvement is not dramatic or permanent
– may also assist in similar diseases causing dementia (ie. Parkinson
disease)
• Tacrine (Cognex)
• Donepezil (Aricept)
• Galantamine/ galanthamine (Reminyl)
• Rivastigmine (Exelon)

N-methyl-D-aspartate
• Drugs within the class known as NMDA blockers
– Memantine (Namenda)
• FDA approved for the treatment of moderate-to-severe
Alzheimer disease
• Once NMDA blockers initiated, an obvious improvement in
basic ADL’s for is observed
– can be used in combination with AChE inhibitors
– observed effects often modest, but improvements tend to aid
caregivers or family members in their interactions with these
individtuals.
• Function:
– guard against overexcitement of NMDA receptors by
brain chemical glutamate.
• Overexcitement of NMDA receptors by high levels of
glutamate is believed responsible for decreased nerve cell
function which invariably results in nerve cell death

Other Rx Interventions
Class Common Meds Purpose Comments
Antipsychotics Haloperidol (Haldol),
risperidone (Risperdal),
olanzapine (Zyprexa),
quetiapine (Seroquel)
Frequently prescribed to help manage psychosis
and agitation. Use is intended to decrease
psychotic symptoms (paranoia, delusions,
hallucinations), screaming, combativeness, and/or
violence.
Antidepressants Depression is often associated with dementia and
tends to worsen the degree of cognitive and
behavioral impairment. Mood enhancement may
play a role in the apparent improvement in
cognition.
Antianxiety Buspirone (Buspar) Prescribed as anxiety is common with dementia benzodiazepines like diazepam (Valium) have
been used to treat anxiety but must be
avoided as they tend to increase agitation in
dementia and cause sedation
Other Selegiline (Eldepryl):
selegiline,
Some studies have reported this med, often used
to treat Parkinsons, may improve behavior,
functional performance, and cognitive function.
Mood enhancement may play a role in the
apparent improvement in cognition.
Antioxidants Vitamin E High doses of vitamin E (1000 units twice daily)
may be beneficial in delaying functional
deterioration in vascular dementia.
Such high doses of vitamin E can cause
bleeding problems in some people. The
addition of vitamin C may enhance the
beneficial effects.
Anti-inflammatory
agents
ibuprofen (Motrin, Advil)
naproxen (Aleve).
Nonsteroidal anti-inflammatory drugs (NSAIDs)
may decrease inflammatory changes that are
common in Alzheimer disease, or they may inhibit
platelets, thereby protecting blood flow in the
brain.

Statins & Memory
• Abstract
• Objective. To review case reports of statin-associated memory loss as well as the available
published evidence for and against such a link.
• Methods. We searched the MedWatch drug surveillance system of the Food and Drug
Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory
loss. We also reviewed the published literature (using MEDLINE) and prescribing information for
these drugs.
• Results. Of the 60 patients identified who had memory loss associated with statins, 36 received
simvastatin, 23 atorvastatin, and 1 pravastatin. About 50% of the patients noted cognitive adverse
effects within 2 months of therapy. Fourteen (56%) of 25 patients noted improvement when the
statin was discontinued. Memory loss recurred in four patients who were rechallenged with the
drug. None of the 60 reported cognitive test results. Two placebo-controlled trials found no
benefits for statins on cognition or disability. One randomized controlled trial of simvastatin found
no effects on cerebrospinal amyloid levels. In one small, randomized study, patients receiving
statins showed a trend toward lower cognitive performance than those receiving placebo. Five
observational studies found a lower risk of dementia among patients receiving statins.
• Conclusion. Current literature is conflicting with regard to the effects of statins on memory loss.
Experimental studies support links between cholesterol intake and amyloid synthesis; observational
studies indicate that patients receiving statins have a reduced risk of dementia. However, available
prospective studies show no cognitive or antiamyloid benefits for any statin. In addition, case
reports raise the possibility that statins, in rare cases, may be associated with cognitive impairment,
though causality is not certain.
– Wagstaff LR, Mitton MW, McClendon Arvik B, and Doraisswamy PM (2003). Statin-Associated Memory Loss:
Analysis of 60 Case Reports and Review of the Literature. Volume 23, Issue 7, July 2003, Pages 871–880
Pharmacotherapy DOI: 10.1592/phco.23.7.871.32720. Retrieved from
http://onlinelibrary.wiley.com/doi/10.1592/phco.23.7.871.32720/full

Statin Case Study #1
Abstract
• Background: There have been a number of published reports of central nervous
system (CNS) adverse effects with statins.
• Case summary: A 79-year-old woman developed paranoia, anxiety, and behavioral
changes ~2.5 weeks after starting atorvastatin 10 mg/d. The patient had no other
medication changes at this time. After 2 months of therapy, the patient
discontinued atorvastatin, and her symptoms fully resolved after 4 days.
• Conclusions: This is the first case report, to our knowledge, describing paranoia as
one of the symptoms associated with statin therapy. Our report suggests an
adverse reaction due to the initiation of atorvastatin via the temporal relationship
between the start of atorvastatin and symptom onset, as well as termination of
therapy and subsequent symptom disappearance. Use of the Naranjo adverse drug
reaction probability scale to assess causality revealed a “probable” association
(score, 5) for this adverse event. This report emphasizes the possibility of paranoia
as a CNS adverse effect due to statin therapy. Statins are frequently used in older
populations and should therefore be considered when such CNS adverse effects
occur during therapy.
– Peters JT, Garwood CL, and Lepczyk MB (2008). Behavioral changes with paranoia in an elderly
woman taking atorvastatin. The American Journal of Geriatric Pharmacotherapy. Volume 6, Issue 1,
March 2008, Pages 28-32. http://www.sciencedirect.com/science/article/pii/S1543594608000032

Case Study #2
Abstract
• Memory loss and cognitive impairment have been reported in the literature in
association with several 3-hydroxy-3-methylglutaryl coenzyme A reductase
inhibitors (statins), but we found no published case reports associated with
rosuvastatin. To our knowledge, this is the first reported case of rosuvastatin-
related short-term memory loss. A 53-year-old Caucasian man with
hypercholesterolemia experienced memory loss after being treated with
rosuvastatin 10 mg/day. He had no other concomitant conditions or drug
therapies. After discontinuation of rosuvastatin, the neuropsychiatric adverse
reaction resolved gradually, suggesting a probable drug association. During the
following year, the patient remained free from neuropsychiatric disturbances.
Clinicians should be aware of possible adverse cognitive reactions during statin
therapy, including rosuvastatin.
• Galatti L, Polimeni G, Salvo F, Romani M, Sessa A, and Spina E (2006). Short-
Term Memory Loss Associated with Rosuvastatin. Pharmacotherapy. Volume
26, Issue 8 August 2006, Pages 1190–1192. DOI: 10.1592/phco.26.8.1190.
Retrieved from
http://onlinelibrary.wiley.com/doi/10.1592/phco.26.8.1190/full

Considering Antipsychotics
• 1.Assess patients for the type, frequency, severity, pattern, and timing of
symptoms. (1C)
• 2.Assess patients for pain and other potentially modifiable contributors to
symptoms as well as for factors such as dementia subtype that may influence
choices of treatment. (1C)
• 3.In patients with dementia with agitation or psychosis, assess response to
treatment using a quantitative measure. (1C)
• 4.Develop a comprehensive treatment plan that includes appropriate person-
centered nonpharmacologic and pharmacologic interventions, as indicated. (1C)
• 5.Only use nonemergency antipsychotic medication when agitation and psychosis
symptoms are severe, are dangerous, and/or cause significant distress to the
patient. (1B)
• 6.Review the clinical response to nonpharmacologic interventions prior to
nonemergency use of an antipsychotic medication to treat agitation or psychosis in
patients with dementia. (1C)
• 7.Before starting nonemergency treatment with an antipsychotic, assess and
discuss with the patient/family/decision maker the potential risks and benefits.
(1C)
8.If a risk/benefit assessment favors the use of an antipsychotic for
behavioral/psychological symptoms in patients with dementia, start treatment at a
low dose and titrate up to the minimum effective dose as tolerated. (1B)

Considering Antipsychotics…
• 9.If a clinically significant side effect of antipsychotic treatment emerges, review the potential risks and
benefits of antipsychotic medication to determine whether tapering and discontinuance of the medication are
indicated. (1C)
• 10.If there is no clinically significant response after a 4-week trial of an adequate dose of an antipsychotic
drug, the medication should be tapered and withdrawn. (1B)
• 11.In a patient who has shown a positive response to an antipsychotic, decisions about possible tapering of
the medication should be made with input from the patient (if feasible) or surrogate decision maker, family, or
other caregiver, with the aim of eliciting their preferences and concerns and reviewing the initial goals,
observed benefit, and side effects of antipsychotic treatment and potential risks of continued use, as well as
past experience with antipsychotic medication trials and tapering attempts. (1C)
• 12.For a patient who has an adequate response of behavioral/psychological symptoms to antipsychotic
treatment, an attempt to taper and withdraw the drug should be made within 4 months of initiation unless
the patient experienced a recurrence of symptoms with prior attempts at tapering of antipsychotic
medication. (1C)
• 13.For a patient whose antipsychotic medication is being tapered, assess symptoms at least monthly during
the taper and for at least 4 months after medication discontinuance to identify signs of recurrence and trigger
a reassessment of the benefits and risks of antipsychotic treatment. (1C)
• 14.In the absence of delirium, if nonemergency antipsychotic medication treatment is indicated, haloperidol
should not be used as a first-line agent. (1B)
• 15.A long-acting injectable antipsychotic medication should not be utilized unless it is otherwise indicated for a
co-occurring chronic psychotic disorder. (1B)
• https://www.medscape.com/viewarticle/862795

Dementia & Communication
• Ten Tips
– Set a positive mood for interaction
– Get the person’s attention
– State your message clearly
– Ask simple, answerable questions
– Listen with your eyes, ears, and heart
– Break down activities into a series of steps
– When the going gets tough, distract & redirect
– Respond with affection and reassurance
– Remember the good old days
– Maintain your sense of humor

iamanalzheimerscaregiver.blogspot.com-

Handling troubling Behavior
• Challenges of caring for dementia are personality and
behavior changes
• meet these by using creativity, flexibility, patience &
compassion.
• helps to not take things personally
• Remember:
– cannot change the person
– Check with the health provider: behavioral problems have an
underlying medical reason
– Behavior has a purpose
– Behavior is triggered.
– What works today, may not tomorrow
– Get support from others

Early Onset Dementia (EOD)
Abstract
• Dementia is characterized by a decline in cognitive faculties and occurrence of behavioral
abnormalities which interfere with an individual's activities of daily living. Dementing
disorders usually affect elderly individuals but may occur in individuals younger than 65 years
(early-onset dementia or EOD). EOD is often misdiagnosed or its diagnosis is delayed due to
the fact that it has a more varied differential diagnosis than late-onset dementia. EOD affects
individuals at the height of their career and productivity and produces devastating
consequences and financial loss for the patient's family as well as society. EOD is not
uncommon and is diagnosed in up to a third of patients presenting with dementia. Most
importantly, some of the causes of EOD are curable which makes the need for a specific and
timely diagnosis crucial. The present chapter presents a systematic approach to the
differential diagnosis of EOD and provides readers with the clinical and neuroimaging
features of these disorders as well as important considerations for their diagnostic
evaluation. Specifically, the nuances of assessing the history and examination are discussed
with careful attention to the various methods of cognitive and behavioral evaluation. A step-
wise approach to diagnostic testing is followed by a discussion of anatomical localization,
which often aids in identifying specific etiologies. Finally, in order to organize the subject for
the reader, the various etiologies are grouped under the general categories of vascular,
infectious, toxic-metabolic, immune-mediated, neoplastic/metastatic, and
neurodegenerative. International Review of Neurobiology
– Fadil, H and Minagar, A, et al (2009). Early Onset Dementia. International Review of Neurobiology.
Volume 84, 2009, Pahttps://doi.org/10.1016/S0074-7742(09)00413-9ges 245-262

Early Onset Dementia
Abstract
• Dementia is is stereotypically associated with older people.
However, in a significant minority it can affect people in their 40s
and 50s, or even younger. Currently there is a lack of awareness,
even among healthcare professionals, and there is a dearth of
appropriate services for such patients. Despite the attention given
to this condition by National Institute for Health and Clinical
Excellence guidelines, provision of specialist early-onset dementia
services in the UK remains patchy. Carers and patients often find
themselves being passed ‘from pillar to post’ between psychiatry
and neurology, and also between adult, old age and liaison
psychiatry. The responsibility for identifying available and
appropriate help is often left with carers. This leads to unnecessary
delays, causes undue distress to patients and places an added
burden on carers.
• Jefferies K and Agrawal N (2009). Early-onset dementia. Advances in
Psychiatric Treatment Aug 2009, 15 (5) 380-388; DOI:
10.1192/apt.bp.107.004572

EOD
• Abstract
• BACKGROUND: It is estimated that 1,200 people under the age of 65 have
been diagnosed with dementia in Norway. This article provides an
overview of the types of dementia frequently seen in younger patients.
MATERIAL AND METHODS: The article is based on a non-systematic search
in PubMed, as well as the authors' own clinical and research experience.
RESULTS: Alzheimer's disease, frontotemporal dementia, vascular
dementia and dementia with Lewy bodies, are the most common types of
dementia occurring more often in younger than in older patients. The
cognitive symptoms are more variable in younger patients than in older.
Only a small percentage of early onset dementia is caused by genetic
factors. There are few diagnostic tools available for this age group and it
takes considerable time to reach a correct diagnosis. Early diagnosis allows
the patient and carer to plan for the future. INTERPRETATION: Physicians
should be aware that dementia can occur in younger people, and more
diagnostic assessments should be developed for this patient group. Better
coordination from the public health authority and municipalities is needed
to provide respite care for early onset dementia patients and their carers.
– Rosness TA, Haugen PK, and Engeal K (2011). Early Onset Dementia. Europe
PMC. DOI: 10.4045/tidsskr.09.0845.
http://europepmc.org/abstract/med/21694746

Hypotheses of EOD
• Global cerebral blood flow, oxidative brain metabolism, and the cerebral
arteriovenous differences of amino acids and ammonia were studied in 20
clinically diagnosed patients with early-onset dementia of Alzheimer type
(DAT). Eleven healthy age-matched subjects and 15 healthy young
volunteers served as controls. The most prominent abnormality in patients
with early-onset DAT was a 44% reduction in the cerebral metabolic rate
of glucose and a fourfold increase of lactate production, whereas cerebral
blood flow and the cerebral metabolic rate of oxygen were found not to be
altered. The cerebral amino-N balance substantially changed in patients
with early-onset DAT, showing a massive loss of amino acids and ammonia
from the brain, which was indicative of excess protein catabolism due to
cell degeneration in the acutely diseased brain. The abnormality found in
glucose metabolism may suggest a perturbed control of glycolytic
breakdown of glucose and its first oxidation step at the pyruvate
dehydrogenase complex level, this thus being of pivotal significance in
early-onset DAT.
• Hoyer S, Oesterreich K and Wagner O (1987). Glucose metabolism as the site of the
primary abnormality in early-onset dementia of Alzheimer
https://link.springer.com/article/10.1007%2FBF00314304?LI=truetype? Journal of
Neurology January 1988, Volume 235, Issue 3, pp 143–148 .

Accurate Dx of EOD
• Abstract
• Early-onset dementia (EOD, <65 years at onset) is a relatively common and
frequently misdiagnosed condition. One reason for misdiagnosis is that
EOD has a more varied differential diagnosis than late-onset dementia
(LOD). For example, Alzheimer's disease (AD), the preponderant LOD,
makes up only about one-third of EODs; the rest are due to vascular
dementias, frontotemporal lobar degenerations, traumatic head injury,
alcohol-related dementia, and a great many other conditions. Another
reason for misdiagnosis is that early-onset AD may have predominant
cognitive deficits other than memory loss and a potential familial
inheritance with spastic paraparesis, seizures, or myoclonus. A third
reason is that EOD often presents with neuropsychiatric features out-of-
proportion to any cognitive deficits. Despite these obstacles, it is
important to accurately diagnose EODs, particularly because they differ in
management and course. Clinicians can successfully diagnose most EODs
with careful cognitive and family histories, mental status and neurological
examinations, and neuroimaging.
– Mendez MF (2006). The Accurate Diagnosis of Early-Onset Dementia. The
International Journal of Psychiatry in Medicine, Vol 36, Issue 4, 2006.
http://journals.sagepub.com/doi/pdf/10.2190/Q6J4-R143-P630-KW41

Early vs Late Onset Dementia
Abstract
• Background: Research on the epidemiology of dementia has focused on the elderly. Few
investigations have studied differences in etiologic frequencies between early-onset dementia
(EOD), with onset at an age of less than 65 years old, and the more common late-onset disorder.
Objectives: To determine relative frequencies and characteristics of EOD versus late-onset dementia
(LOD; age of onset ≧65 years) diagnosed in a large memory disorders program over a 4-year period.
Methods: We reviewed medical records, including an extensive neurobehavioral and neurological
evaluation, of all patients seen at a large Veteran’s Affairs Medical Center Memory Disorders clinic
between 2001 and 2004 and assessed demographic variables, final diagnoses, presence of
dementia, and differential diagnosis of dementing illnesses. Results: Among 1,683 patients
presenting for evaluation of an acquired decline in memory or cognition, 948 (56%) met established
clinical criteria for a dementing illness. About 30% (n = 278) of these had an age of onset of <65
years, compared to 670 with LOD. Patients were predominantly male (98%). Compared to the late-
onset group, the EOD patients were less severely impaired on presentation, but they did not differ
in gender distribution or educational background. The EOD group had significantly more dementia
attributed to traumatic brain injury, alcohol, human immunodeficiency virus (HIV), and
frontotemporal lobar degeneration compared to the LOD patients. In contrast, the LOD group had
significantly more Alzheimer’s disease compared to the EOD group. Conclusions: This study,
conducted at a Veterans Affairs Hospital, is the largest series to date on EOD, and found a previously
unexpectedly large number of patients below the age of 65 with cognitive deficits and impaired
functioning consequent to head trauma, alcohol abuse, and HIV. These findings highlight the
differential distribution and importance of preventable causes of dementia in the young.
– McMurtray A. · Clark D.G. · Christine D. · Mendez M.F. (2006). Early-Onset Dementia: Frequency and Causes
Compared to Late-Onset Dementia. Dementia and Geriatric Cognitive Disorders. 2006;21:59–64
https://doi.org/10.1159/000089546 .

4 Genes Implicated in EOD
Summary
• Clinical differential diagnosis of early-onset dementia (EOD) includes familial Alzheimer disease
(FAD) and hereditary prion disease. In both disease entities, postmortem brain histopathological
examination is essential for unambiguous diagnosis. Mutations in the genes encoding the
presenilins (PS1 and PS2) and amyloid precursor protein (APP) are associated with FAD, whereas
mutations in the prion protein (PrP) gene are associated with prion disease. To investigate the
proportion of EOD attributable to known genes, we prospectively (i.e., antemortem) screened
these four genes for mutations by sequencing genomic PCR products from patients with EOD
before age 60 years. Family history for dementia was positive (PFH) in 16 patients, negative (NFH) in
17 patients, and unknown (UFH) in 3 patients. In 12 patients, we found five novel mutations (in PS1,
F105L; in PS2, T122P and M239I; and in PrP, Q160X and T188K) and five previously reported
mutations (in APP, in three patients who were most likely unrelated, V717I; in PS1, A79V and
M139V; and in PrP, P102L and T183A) that are all considered to be disease causing. Of these 12
patients, 9 had PFH. This indicates a detection rate of 56% (9/16) in patients with PFH. We found
two mutations (APP V717I) in two of the three UFH patients, and only one mutation (PrP T188K) in
1 of the 17 patients with NFH. We conclude that because of the lack of specific antemortem
diagnostic markers for FAD and hereditary prion disease, all four genes should be included in a
molecular diagnostic program in patients with EOD who had PFH.
– Finckh U, Mueller-Thompson T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C,
Nitsch RM, and Gal A (2000). High Prevalence of Pathogenic Mutations in Patients with Early-Onset
Dementia Detected by Sequence Analyses of Four Different Genes. AJHG Vol 66, Issue 1, Jan 2000, pp i-ii, 1-
346. http://www.sciencedirect.com/science/article/pii/S000292970762237X

Citations
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(2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease:
systematic review and meta-analysis of community-based cohort studies. The British
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Dementia. International Review of Neurobiology. Volume 84, 2009,
Pahttps://doi.org/10.1016/S0074-7742(09)00413-9ges 245-262
• Finckh U, Mueller-Thompson T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G,
Alberici A, Hock C, Nitsch RM, and Gal A (2000). High Prevalence of Pathogenic Mutations in
Patients with Early-Onset Dementia Detected by Sequence Analyses of Four Different Genes.
AJHG Vol 66, Issue 1, Jan 2000, pp i-ii, 1-346.
http://www.sciencedirect.com/science/article/pii/S000292970762237X
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Citations
• Hoyer S, Oesterreich K and Wagner O (1987). Glucose metabolism as the site of the primary abnormality
in early-onset dementia of Alzheimer
https://link.springer.com/article/10.1007%2FBF00314304?LI=truetype? Journal of Neurology January
1988, Volume 235, Issue 3, pp 143–148 .
• I.G. McKeith, D. Galasko, K. Kosaka, E.K. Perry, D.W. Dickson, L.A. Hansen, D.P. Salmon, J. Lowe, S.S. Mirra,
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• Jefferies K and Agrawal N (2009). Early-onset dementia. Advances in Psychiatric Treatment Aug 2009, 15
(5) 380-388; DOI: 10.1192/apt.bp.107.004572
• McMurtray A. · Clark D.G. · Christine D. · Mendez M.F. (2006). Early-Onset Dementia: Frequency and
Causes Compared to Late-Onset Dementia. Dementia and Geriatric Cognitive Disorders. 2006;21:59–64
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Journal of Psychiatry in Medicine, Vol 36, Issue 4, 2006.
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