From pages 234-235 in Memory's Voice (keep in mind that this was written in 1992):
"As the disease progresses, the lacunae of memory become less sub-
tle. Short-term lapses begin to appear. A patient may forget an
appointment he made a few hours earlier. As is common with simple
aging, some individuals compensate by writing down everything they
want to remember. Insidiously, the disease begins to consume pieces of
more permanent memory-the name of a grandchild is confused with
that of a brother; a doctor's address is substituted for that of a priest. A
watchmaker can still repair watches, but he doesn't know where he
works or that this is the means of his livelihood. At home, he no longer
pays the bills and ultimately forgets daily necessities such as when to
take out the trash. Throughout the early deterioration of life, patients
seem to sense the havoc the disease is wreaking. They seem to reach
for what is missing and are often anxious in their helplessness. But it is
the family members who feel the greatest anxiety and helplessness and
on whom the burden of the patient's daily care usually falls. Finally, the
results of diffuse brain destruction, no longer limited to memory loss,
extend to the loss of sensations and emotion, impaired movement, and
uncontrolled bodily functions.
To the student of memory, Alzheimer's disease presents a tempting
target. But is it, in fact, truly a disease of memory, or is memory impair-
ment a characteristic symptom simply because the disease affects so
many brain regions? Yet, doesn't the course of Alzheimer's track the
permanence of memory? At first patients forget what they learned a
few weeks ago, then a few days ago, and finally only moments ago.
They progressively lose the ability to consolidate and store a memory
for any length of time. This is undoubtedly due to destruction of
the hippocampus by plaques, as well as damage to other brain areas
where plaques are found, but there is no one-to-one correspondence
between plaque deposit and symptom occurence. Furthermore, in
older people plaques can appear without any Alzheimer's symptoms.
Pursuing the relation of Alzheimer's disease to memory loss fur-
ther, we can ask if the disease, at its onset, affects molecular events
unique to memory. Perhaps there is a subtle loss in sensory discrimina-
tion of particular odors, sound, or colors. Maybe there is a slight loss of
coordination or loss of balance. Recent evidence suggests that a pri-
mary site for the disease could be protein kinase C, the enzyme that our
laboratory has implicated in associative memory. Saitoh and his
colleagues reported a deficiency in this enzyme within cells taken from
Alzheimer patients as compared to nonpatients of the same age. Other
workers have begun to observe hints of impairment in the biochemical
steps required to generate the second messengers that activate protein
kinase C. Still other investigators have shown that biochemical steps in
the formation of beta-amyloid, a key molecule in plaque formation,
involve protein kinase C activation. A genetic basis for Alzheimer's dis-
ease has also been linked to the beta-amyloid protein in a small per-
centage of cases. There may be in every human a potential for any one
of many molecular steps in our neurons to break down. With age, the
probability for one or more of these steps to go awry may increase,
accounting for the increasingly high incidence of Alzheimer's disease
with age. An analogous biochemical vulnerability may explain the
increasingly high incidence of cancer with age."
