XIII ALZHEIMER'S DISEASE (SENIUM PRÆCOX) THE REPORT OF A CASE AND REVIEW OF PUBLISHED CASES* BY SOLOMON C. FULLER, M.D. The first published case presenting the combination of clinical symptoms and microscopical changes discussed in this paper was reported by Alzheimer (1) in 1906. Since then similar observations have been recorded by Bonfiglio (2), Sarteschi (3), Perusini (4), Barrett (5), Alzheimer (6), Bielschowsky (7), Lafora (8), Fuller (9), Betts (10), Schnitzler (11), and Jansens (14). The case described here is included as an example of Alzheimer's disease in the report on a group of 93 brains examined with reference to origin, diagnostic significance and finer structure of so-called senile or Fischer's plaques. Owing to the variety of psychoses included in the earlier communication, the large number of clinical abstracts and the abbreviated manner in which the case was presented, a further report is undertaken. The chief reason, however, for this elaboration and the review of all published cases known to the writer, is furnished by the lively interest shown in the type of mental disorder to which Alzheimer was the first to call attention. The cases from the literature are given below in chronological order, the clinical abstracts in full, and the anatomical findings summarized in the discussion. While more or less definite mental symptoms and structural alterations are referred to in this paper, the recorded cases are too few even these showing important variations-to warrant maintaining anything comparable to the paradigm of general paresis. The earlier reports, along with other details mentioned in their microscopical descriptions, emphasize the combination of miliary plaques with a certain basket-like appearance of ganglion cells occasioned by a peculiar alteration of intracellular neurofibrils. But within the present year† Alzheimer himself has published a case in which numerous large miliary plaques of the brain were a striking feature, but in which no ganglion cell exhibited the peculiar type of alteration. (Vide infra Alzheimer's second case.) The last recorded observations (Schnitzler's case) note the Alzheimer degeneration of ganglion cells, but not a single plaque was found in the many areas of the brain examined. The busy delirium, excitement and confusion which *This paper is reprinted by courtsey of the Journal of Nervous and Mental Diseases, where it was first published in the July and August, 1912, numbers. † 1911. have characterized the clinical course of some of the cases have been wanting in others, their place being taken by an apathetic dementia. The aphasic symptoms and ideational apraxia have also failed in some of the cases. Nevertheless, when this has been said, it must also be said that the clinical and anatomical findings offer a striking similarity. Although the total number of cases is small upon which the conception of this type of mental disorder is based, the assumption of a clinical type or subgroup is not altogether unwarranted. These cases clearly indicate that psychoses occurring in or about the period of senium are a rich field for clinical and anatomical research. The Westborough case is presented as cumulative data toward the isolation of a type which while lacking at present some of the postulates of a disease entity may yet crystallize into such. W. S. H., No. 9,378, a man 56 years of age, for some time previous to his final breakdown (about two years), had shown a memory defect, short periods of apparent unconsciousness or dream-like states, verbal amnesia and occasional paraphasia, but had been able to continue at work as a laborer on a farm where he had been employed for many years. His sister states that the memory defect had been gradual, and while at first the short periods of confusion (of a few minutes' duration), in which he spoke in a paraphasic or senseless manner, were only seldom observed, of late these had become very frequent. Recently, even when there was no apparent mental confusion, he often seemed unable to find the proper word or words to employ in ordinary conversation. He would often search for things which lay directly before him, and would use familiar objects incorrectly (apraxia). Within the last six months when he had visited his sister's home, he would relate to her, over and over again, the same experience within the course of a few minutes, apparently forgetting that he had already done so. On going to bed, he would make separate bundles of his clothing, placing one here, another there, in out-of-the-way places, and in the morning could not remember what he had done with his things. Twenty years ago he had separated from his wife on account of her infidelity. This affair had worried him quite a little, but he formerly never spoke of it to any one. Of late, however, he constantly referred to his wife in conversation, wondered where she was and whether he had done the proper thing in leaving her. As a result he was slightly depressed. It appears that his wife was certainly at fault, while he has always borne a reputa tion for integrity and industry. He was the father of three children by this union, one of which died in infancy from cerebrospinal meningitis, the others now of age and in good physical and mental health. About ten days prior to admission to hospital, he had a "mild attack of influenza with which marked mental symptoms were associated. During this attack he had been very restless, particularly at night, roamed about the house, talked much about his work, and went through movements as though employed at his usual daily tasks. Finally, he began to tear the bed-clothing, was manifestly disoriented and confused, apparently forgot movements employed in dressing and feeding himself and lost control of bladder and rectal function, or at least performed these latter functions without regard to ordinary rules of decency and tidiness. The mother of patient died of apoplexy at th eage of 61, father at about 65 from an affection of the stomach. No other family history of importance elicited. On admission to Westborough State Hospital, Jan. 27, 1911, he was in a fairly well nourished condition, but looked older than his stated age (56) and presented in his person the appearance of neglect. The gait was rather unsteady but not characteristic of anything more than a general weakness combined with what appeared to be a senile trepidancy; no evidence of paralysis detected. A systolic murmur, best heard at the apex, a full and rapid but regular pulse, firm radial and temporal arteries were present. Respiratory movements were of the costal type; broncho-vesicular breathing and a few râles on right side. The pupils were slightly irregular in outline but of equal diameter, reacting sluggishly to light, the right more sluggishly than the left. Accommodation tests unsatisfactory owing to lack of proper cooperation. Acuity of vision could not be determined. The patient also failed to cooperate in tests for hearing and for the same reason integrity, or the extent of impairment, of taste, olfactory and tactile sensibility could not be definitely determined. As noted above, there were no paralyses, no contractures. Muscular development was fair but rather flabby. Coordination tests were poorly executed; no Romberg; tendon reflexes increased. No history of lues or cerebral insult was obtained. He had used alcohol moderately. When first seen by examining physician he was very somnolent and could be aroused only with difficulty. Mentally he was not only dull but apparently indifferent, was disoriented for time, place and persons and was without grasp on his surroundings. Speech reactions were slow, indistinct-often degenerating into a scarcely audible jargon-data frequently incorrect. There was often a logoclonic repetition of the last word of a sentence or last syllable of a word, and with fatigue, easily evoked he became paraphasic. Memory defect was marked for the grossest events of his life, the recent as well as the remote. Q. What is your age? A. Charles E. G.-. Q. Where were you born? then finally, Watertown. A. Unintelligible muttering, Q. Where is your home? A. My home was born in Boston I suppose by my mother and her name was Stagpole. (Maiden name of mother was Stackpole.) Q. Where is your home? A. I have no home but hopple popple home all the time. Q. Where are you now? A. I know I am from another room as where from another room. Q. What kind of a place is this? A. Kind of a wooded play, Etc. He was able to name and indicate the use of objects shown him-pencil, knife, keys, watch. When given pencil and paper and directed to write his name and address, he grasped the pencil in a proper manner, placed the paper on a hard surface and laboriously made a few marks but did not form a single letter. Questioned whether or not the marks were intended for his name he replied "yes." Repeated attempts were equally futile. Jan. 28, 1911, the day following admission, he was a little brighter mentally and for a while during the interview with examiners he answered questions readily and in an orderly manner, but he was still disoriented. He could not tell how long in hospital, the nature of the institution, or remember that he had seen one of the examiners on the evening previous. He showed no concern when informed as to the character of the hospital. "Garfield is president" and he had "never heard of Roosevelt." He did not know whether his wife was dead or alive, at first maintaining that she was alive, later that she had been dead two years. During the interview, he frequently exhibited a verbal amnesia and was occasionally paraphasic. He could name objects shown him-bedroom furniture and small articles. such as are carried on the person-and execute simple commands, but easily became confused with more complex tests, such as: three pieces of paper of different sizes of which he was directed to tear up the largest, give the middle sized one to examiner and put the other in the pocket of his bath robe. Go to the window, knock on the pane, come back and sit down, etc. Feb. 3, 1911. restless at night; clothing. Following the last note he was very noisy and frequently confused and destroyed the bed Feb. 7, 1911. Rapid physical and mental failure; very unsteady on feet; for two days previous he had failed to respond to all questions; remained in bed, constantly disturbing the bedclothing or moving his arms about in a purposeless manner. Frequent unintelligible mutterings; extremely resistive. Feb. 8, 1911. Pronounced clonic spasms of the left shoulder; clouding of consciousness; labored breathing; difficulty in swallowing; extreme resistance. Feb. 9, 1911. Death with symptoms of broncho-pneumonia. Autopsy 16 hours post mortem. Anatomical Diagnosis.—Chronic external pachymeningitis, hernia of Pacchionian granulations through the dura, chronic hypertrophic leptomeningitis, pial congestion and moderate pial edema, advanced cerebral arteriosclerosis, regional atrophies of cerebrum (frontal right and left, and temporal left); chronic endocarditis; bronchopneumonia; chronic perihepatitis; chronic perisplenitis; moderate chronic interstitial nephritis. The brain, with pia attached and before sectioning, weighed 1,445.8 grams. While within the accepted range of normal weights, focal cerebral atrophies were displayed in the frontal regions and in the left temporo-sphenoidal lobe, atrophies not accounted for by previous hæmorrhage, softening gumma or new growth. Section of cerebrum, pons, medulla and cerebellum were negative for coarse focal lesions other than the atrophies mentioned. The larger vessels of the base and many branches of the mesial and convex surfaces of the cerebrum were sclerotic, tortous and did not collapse on section, besides exhibiting atheromatous patches which imparted a beaded effect. The lining of the ventricles was smooth; the ventricular capacity within normal range; cysts of choroid plexus. The spinal pia was slightly clouded and presented several small osteomata, occurring chiefly in the ventral portion of the thoracic distribution of the membrane. The cord shared in the general congestion, other than this offering no gross lesions. The microscopical examination revealed the following: Mesoblastic Apparatus.-The pia in alcohol-fixed sections stained with toluidin (frontal, precentral, temporal and calcarine regions) shows that the thickening noted macroscopically is due chiefly to a proliferation of connective tissue fibers and fibroblasts, presenting a meshed appearance in which are cells of variable size containing lipoid granules (Abraumzellen). The frontal pia presents the greatest number of such cells, though they are by no means scant in the other areas examined. Not infrequently they are found in great numbers in the portion of the membrane immediately adjacent to the cerebrum, but dis |