XIV

FURTHER OBSERVATIONS ON ALZHEIMER'S DISEASE.*

BY SOLOMON C. FULLER, M.D., AND HENRY I. KLOPP, M.D.

One of us has recently described what we believe to be the tenth recorded case of so-called Alzheimer's disease,' that is, certain histopathological alterations of the brain indicative of senile involution associated with clinical symptoms such as are exhibited in the severest form of senile dementia, but appearing in comparatively young persons. Included among the clinical symptoms are phenomena suggestive of coarse focal lesions of the brain aphasic and apractic disturbances-which have not been accounted for by coarse focal lesions at autopsy.

For purposes of comparison there were added to the report of the first Westborough case the clinical histories of all cases then known to us, ten from foreign literature and two from American sources, together with a critical analysis of these histories and their associated anatomical findings. It was shown that despite certain basic chracteristics, more or less present in all of the cases, essential differences existed which precluded for the present any dogmatic statement as to the exact clinical grouping of these cases, as well as any claim for a definite gross or histo-pathological anatomy. Nevertheless, in so far as one may be justified in correlating anatomical changes with clinical symptoms, there is much in the finer anatomy as a whole to indicate a psychosis dependent in a great degree upon involutional changes in the brain and blood vascular apparatus, while the clinical histories offer many features which we are accustomed to associate with senile mental disorders.

The first case of Alzheimer's disease to be recognized as such at Westborough was clinically and anatomically quite comparable to the first case reported by Alzheimer' and the group of cases later collected and published by Perusini.' The case which forms the subject of this communication did not exhibit anatomically the peculiar type of intracellular neurofibril alteration common to the majority of reported cases, and in this respect is like Alzheimer's second case, the only other to our knowledge in which the basketlike appearance of many ganglion cells was wanting. So-called senile plaques, while present, were neither large nor numerous, and differed slightly in structure from plaques as usually described, but

*Presented in abstract at the sixty-eighth annual meeting of the American MedicoPsychological Association, Atlantic City, N. J., May 28-31, 1912, and printed here by courtesy of he Association.

exhibited among themselves a great degree of uniformity. Moreover, the mode of onset and much of the clinical course suggest that certain exogenous toxic factors, which as a rule we do not link with the exciting or even the predisposing causes of senile psychoses are, perhaps, more frequently operative than has been supposed.

Before going on to the history of this case we quote from the paper referred to above' a brief summary of the leading clinical features of all of the cases as revealed by the literature: "About middle life or slightly past, with one exception where the onset was in early adult life, memory defect, disturbance of retention and general mental weakening set in and progress to a marked dementia, in some of the cases slowly, in others rapidly. Early in the course of of the affection aphasic disturbances-verbal amnesia, occasional paraphasia and jargon, impairment of ability to comprehend spoken language, graphic disturbances, verbal and literal preservation-ideational apraxias and agnosia develop, varying from time to time in severity but never as intense or consistent as the speech disturbances and apraxias originating from coarse focal lesions of the brain. Mental confusion with some delirium, lack of bladder and rectal control* without evidence of limb paralyses, good preservation of gross muscular strength, considerable motor activity and general restlessness have been striking features of the majority of the cases. Auditory and visual hallucinations with apprehensive delusions based upon them and spatial as well as temporal disorientation have been, in instances, likewise characteristic. Disturbances of the motor projection paths were slight or absent; if occurring at all usually appeared late, even then were often transitory. In a few instances motor disturbances have been noted as residua of epileptiform convulsions. Convulsions with loss of consciousness, with one excep tion, have not been observed in the terminal stage, epileptiform attacks and muscular twitchings being recorded. With exception of Case II, luetic infection does not appear in the anamneses. Alcoholic indulgence while mentioned as moderate in Cases VI and VIII and pronounced in II and VII seems to have played no role, or, at most, a minor one."

So far as we are aware, these still remain the salient clinical leatues of this type of cases. The original anatomical picture, on the other hand, has undergone considerable modification, although preserving the close kinship with the histo-patic'ogical alterations. of senile cerebral involution. The anatomical changes of this

*Not necessarily the result of paralyses, but rather the untidiness that is commonly associated with confused states and marked dementia.

†The case here reported is also an exception.

atypical senile group together with what may reasonably serve as a criterion for a senile psychosis will be discussed more in detail in the further course of this paper.

The history of the second case of Alzheimer's disease to come to autopsy at Westborough State Hospital is as follows:

No. 9879, a woman of fifty-six years was admitted to Westborough State Hospital December 10, 1911, on a transfer from the Arlington Health Resort, a private institution for nervous and mental diseases, where she had been a patient since August 8, 1911.

It is reported that throughout life the patient had been of the so-called nervous temperament-quick and sensitive-but until the present illness had usually exercised good self-control. In 1883, while descending a flight of stone stairs she fell, striking the coccyx and has had soreness in that region ever since. Some twenty-five years ago she received rather painful injuries in an accident, she was thrown from a moving carriage, sustaining extensive lacerations about the head, one of which nearly severed an ear, and was dragged for a considerable distance over the granite paved blocks of the street. She was unconscious for twenty-seven days after the accident, but no history of paralysis, speech disturbance or amnesias following the occurrence was elicited. During several years thereafter she suffered severe periodical headaches at intervals of about three months, the attacks lasting on an average of three days and each leaving her quite exhausted physically. In about three days after the cessation of the cephallagia she would regain her usual health. These periodical headaches, however, had long since ceased. In 1909 she had an attack of broncho-pneumonia, said to have been of short duration and from which she made a good recovery, her general health, save for habitual constipation, remaining good until the onset of the present illness, in May, 1911. At that time a particularly malignant streptococcic tonsilitis was prevalent in Boston and its vicinity, a form of tonsilitis which often proved fatal to infected persons over fifty. A son-in-law, in whose household the patient lived, and his wife (her daughter) contracted the infection, and our patient undertook their nursing, the care of a young grandchild and the management of the household. After a short while she, too, developed a sore throat which, it appears, was of a milder type. At any rate for the reason of her many responsibilities, her friends state, she did not "give in to it," continuing to care for the sick members of the family and ordering the household affairs.

June 23, 1911, the son-in-law died as the result of the malignant tonsilitis. Almost immediately thereafter the patient developed an articular rheumatism affecting the legs, arms and hands. Even then she did not take to bed, for she was very busy with preparations for changing the residence of the family, most of the work devolving upon her since the daughter, though recuperating, was still not strong. The arthritis persisted for about a month.

August 1, 1911, she was free from pains in the joints, but was in very poor physical condition and was extremely nervous. For several weeks there had been a progressive asthenia, rapid emaciation and marked insomnia. For about a month, although retiring at a late hour, she could not sleep after 3 A.M., when, because of the restlessness engendered by the loss of sleep, she would get up and begin the day's work at that hour. Meanwhile, in addition to rather vague and general apprehensions, she was particularly apprehensive as to the future of her daughter and grandchild, now that their breadwinner and natural protector was gone, an apprehension far in excess of the normal. Always possessing a fear of hospitals of any nature whatever, this feeling became accentuated. From her impaired physical condition she concluded that a serious illness was imminent. There was also a sense of impending death, for she frequently gave directions to her daughter for the disposition of her belongings in case anything happened to her.

August 3, 1911, certain disorders of speech were noted, described by friends as "peculiar." On questioning the relatives it was learned that