This was a lecture in the course "Significant Medical Conditions in Seniors" presented at Peer Learning in Chapel Hill, NC, USA in 2016 by Michael C. Joseph, MD, MPH.

1. Alzheimer’s Disease
Michael C. Joseph, MD
(Peer Learning)
September 21, 2016

2. Outline
 DEMENTIA
− Definition
− Causes
− Workup
 ALZHEIMER’S DISEASE
− Epidemiology
− Historical Perspective
− Symptoms
− Treatment
− Research
 RESOURCES
 CREDITS

3. Dementia
Definition
 A general loss of cognitive abilities,
including impairment of memory and one
of the following:
−aphasia (speech disturbance);
−apraxia (word mistakes);
−disturbances in:
 planning
 organizing
 abstract thinking abilities.

4. Mini-Mental State Examination
(MMSE) - Tasks
 Orientation to Time and Place.
 Repeat the names of 3 common subjects, and
recall them later.
 Spell the word “w-o-r-l-d” backwards.
 Name a “pencil” and “watch”.
 Repeat the following “No ifs, ands, or buts”.
 Follow a 3-stage command.
 Read and obey: “write a sentence”; “close your
eyes”.
 Copy a design (2 overlapping pentagons).

5. Alzheimer’s Disease
Definition
 Dementia of insidious onset and
gradually progressive course;
 With histopathological brain tissue
changes (neuropathology) characteristic
of Alzheimer’s Disease (AD);
 Not due to other central nervous system,
systemic, or substance-induced conditions
known to cause dementia.

6. Alzheimer’s Disease
Historical Perspective
 In 1901, the German psychiatrist Alois Alzheimer
identified the first case in a 50 year old woman,
Auguste Dieter. He followed her case until she died
in 1906, when he first reported on it.
 During the next five years, 11 similar cases were
reported in the medical literature, some of them
already using the term Alzheimer’s Disease (AD).
 For most of the 20th century, the diagnosis of AD was
reserved for patients between the ages of 45 and 65
with dementia.
 Eventually, the term AD was formally adopted in
medical nomenclature to describe individuals of all
ages with a typical symptom pattern, disease course,
and neuropathology.

7. Alzheimer’s Disease
Famous Cases
 Ronald Reagan, Charlton Heston, Glen
Campbell, Rita Hayworth
 Pat Summitt, Perry Como, Charles Bronson,
Norman Rockwell
 Sugar Ray Robinson, Aaron Copland, Estelle
Getty, Peter Falk
 Jimmy Stewart, Eddie Albert, E. B. White,
Rosa Parks
 James Doohan (“Star Trek”), Casey Kasem,
Burgess Meredith, Gene Wilder

8. Alzheimer’s Disease
Brain Pathology
 The major pathologic changes are:
−cerebral atrophy (shrinkage of the brain gray
matter);
−loss of neurons (brain cells) with resulting
vacuoles (spaces in the brain substance);
−amyloid protein plaques;
−neurofibrillary tangles (intracellular
accumulations of brain proteins);
−paired spiral filaments, known as tau proteins.

9. Alzheimer’s Disease
Genetics
 Genetic analysis may identify two genes:
−one gene codes for the protein Apo E and in
two forms increases or decreases the risk
of AD;
−the other gene codes for amyloid protein.
 There is another rare gene that codes for
“Early Onset AD”, rarely in the 3rd or
4th decade of life.

10. Alzheimer’s Disease
Risk Factors
Genetics (70% of cases);
Head injuries;
Depression;
Hypertension;
Smoking;
Slow viruses/Prions;
Air pollution (?).

11. Alzheimer’s Disease
Diagnosis
 Alzheimer’s Disease (AD) is often the diagnosis
after other causes of the dementia are ruled out.
 Patients are then given the diagnosis of
“Possible AD” or “Probable AD” depending on
the severity of their symptoms.
 Research using PET scans have shown early
interaction of the plaques and tangles, and may
help in early diagnosis and treatment.
 AD is definitely diagnosed only post-
mortem, although the MRI can be strongly
suggestive.

12. Alzheimer’s Disease
Subtypes
 “Early Onset”:
− beginning before age 65 (4-5 % of cases).
 “Late Onset”:
− beginning after age 65 (about 6% of all adults).
 Subcategorized on the basis of accompanying features:
− delirium;
− delusions;
− depressed mood;
− behavioral disturbances;
− or none (uncomplicated).

13. Alzheimer’s Disease
Epidemiology
 Advancing age is the major risk factor:
− the risk of AD doubles every 5 years after 65.
 Women have a higher risk of developing AD, especially after age 85.
 AD in the U.S.:
− The group with the highest risk, over 85, is the fastest growing age group;
− Cases increase from 19% in the 75-84 year age group to 42% in those
older than 84;
− It involves 13% of those over 65 (5 million in 2015), and will increase to
20% in 2030.
− AD cost an estimated $100B per year in the U.S. in 2015.

14. Alzheimer’s Disease
“Pre-dementia”
“Senior Moments” (lay diagnosis):
−forgetting things occasionally;
−misplacing items sometimes;
−minor short-term memory loss;
−inability to acquire new information;
−subtle problems with executive functions:
 attentiveness;
 planning;
 abstract thinking.
Mild Cognitive Impairment (MCI):
−may be revealed by neuropsychiatric testing up to 8 years
before the diagnosis of AD.

15. Alzheimer’s Disease
Early Symptoms
 The dominant early feature of AD is usually memory loss,
particularly for recent memories;
 Confusion in unfamiliar situations;
 Apraxia: difficulties in coordination, planning, and execution;
 Loss of fine-motor abilities, such as writing, drawing, dressing;
 A subtle loss of interest or withdrawal from previous activities;
 Language difficulty:
− words are jumbled and sentences meaningless;
− dysarthria (non-fluent speech);
− Repetitive questions and/or topics;
− poor comprehension;
− agrammatical phrases;
− difficulty naming objects.

16. Alzheimer’s Disease
Mid-course Symptoms
 Impaired long-term memory;
 Loss of insight into the AD process (anosognosia);
 Behavioral problems, such as:
− Wandering;
− Agitation, aggression, crying spells;
− Resistance to caregiving;
− Paranoia, delusions.
 Disturbing events like:
− not recognizing family members;
− leaving the stove turned on;
− placing food in the oven without turning it on;
− exhibitionism or other actions of a sexual nature.

17. Alzheimer’s Disease
Late Symptoms
 Frontal lobe dysfunction, with:
− gait dysfunction;
− abulia (an absence of willpower or an inability to act decisively);
− incontinence.
 Patients eventually become:
− akinetic (with absence, loss, or impairment of the power of voluntary
movement);
− mute;
− unresponsive;
− bedridden.
 The median time of survival from onset is approximately 8
years.
 The cause of death is usually an external factor, such as
infected pressure ulcers, dehydration, or pneumonia - not AD
itself.

18. Alzheimer’s Disease
Treatments
 The drugs Namenda, Aricept, and others
were developed in clinical trials of AD
patients.
 They do not change the status or progress of
the brain lesions - and this is specifically
stated on both FDA drug labels.
 They affect only the clinical symptoms in
mild or moderate AD patients.

19. Alzheimer’s Disease – Prevention (I)
Exercise regularly;
“Healthy”, Japanese, or Mediterranean diet;
Maintain a healthy weight;
Stop smoking;
Maintain a normal blood pressure;
Control diabetes and blood cholesterol levels;
Treat depression;
Cognitive training:
social and intellectually stimulating activities.

20. Alzheimer’s Disease – Prevention (II)
• A 4-year study of 700 priests and other
religious staff looked at the impact of
activities like – listening to the radio, reading
newspapers, playing puzzle games, and
visiting museums. The risk of AD was 47%
lower for those who did those activities more
often.
• An active brain may prevent AD by
establishing “cognitive reserve” (flexibility
to compensate after impairment) or creating
new neuron connections.

21. Alzheimer’s Disease – Prevention (III)
• Vitamins & Supplements (?)
• Theoretically, antioxidants may help prevent
damage from “free radicals” that build up in brain
cells. But clinical trials of Vitamin E, vitamin C, B
vitamins, ginkgo biloba, and Coenzyme Q have all
shown no effect in preventing or slowing AD.
• Resveratrol, a compound found in red grapes and
some supplements, may help protect the brain.
Observational studies have shown that moderate
red wine consumption lowers the risk of AD.
Animal studies have shown that resveratrol can
reduce beta-amyloid deposits in the brain, and
the National Agency on Aging (NIH/NIA) will test its
effects in people with AD.

22. Alzheimer’s Disease - Research (I)
A recent UCLA study of 876 men and women aged
65 or older found that those who were more
physically active had a 50% reduced risk of
developing AD.
Another study of nearly 900 men and women with an
average age of 71 found that those who exercised
moderately or vigorously over 5 years performed on
a par with someone a decade younger on tests of
memory and other brain skills.

23. Alzheimer’s Disease - Research (II)
As we age, the hippocampus (an area of the brain linked to
memory) shrinks – leading to memory problems and possibly
dementia. When previously sedentary men and women aged 50
to 80 years walked around a track 40 minutes each day 3 times
per week for 6 months their hippocampi increased in size. A
control group who did not walk had smaller hippocampi than
when they started.
An experimental drug called aducanumab dramatically reduced
the toxic plaques found in the brains of people living with
Alzheimer's disease, according to results of an early-stage
clinical trial designed to test safety and tolerability rather than
effectiveness.
Alzheimer’s Association International Conference® 2015
(AAIC)

24. Alzheimer’s Disease
RESOURCES
Clinical Studies
Duke University Bryan Alzheimer’s Disease Research Center
General Information, Referrals, Clinical Trials
Alzheimer’s Association (www.alz.org)
(800) 272-3900
Caregiver’s Support
Alzheimer’s Foundation of America (AFA) (http://www.alzfdn.org)
(866) 232-8484
National Institute on Aging (NIH)
https://www.nia.nih.gov/alzheimers/
Preventing Alzheimer’s Disease
Alzheimer’s Disease Education and Referral Center (ADEAR) Center
www.nia.nih.gov/alzheimers

25. CREDITS
 AARP Bulletin (September 2016)
 Alzheimer’s Association (www.alz.org)
 Alzheimer’s Foundation of America (AFA) (http://www.alzfdn.org)
 National Institute on Aging
 https://www.nia.nih.gov/alzheimers/publication/preventing-alzheimers-disease/search-alzheimers-prevention-strategies
 Dorland’s Illustrated Medical Dictionary (29th Edition). W. B. Saunders, Co. (1994)
 Early Diagnosis of Dementia. K. Santacruz, MD, D. Swagerty, MD, MPH. (Am Fam Physician 2001; 63:703-13, 717-8.)
 Neuroanatomy through Clinical Cases. Hal Blumenthal, MD, PhD. Sinauer Associates, Inc. (2002).
 https://en.wikipedia.org/wiki/Alzheimer%27s_disease