Final Diagnosis: FTLD-U

Frontotemporal Lobar Degeneration with Ubiquitin-Positive Inclusions (FTLD-U). Lewy Body Disease, Braak & Braak Stage 3/6, consistent with idiopathic Parkinson's Disease. Cerebral Amyloid Angiopathy, Focal, Moderate (Vonsattel Grade 2 of 4). Atheroslerotic Vascular Disease, Moderate.

Comment: The neuropathologic post-mortem examination revealed cortical atrophy and the presence of ubiquitin-positive, TDP-43 positive inclusions which form the histologic features of FLTD-U. They are also present in superficial layers of the parahippocampal gyrus, which shows moderate to severe neuronal loss and gliosis, as well as superficial vacuolation (1, 2). Immunohistochemistry for ubiquitin and TDP-43 reveals numerous cytoplasmic (crescentic) inclusions as well as positive neurites and granular positivity of neuropil. The frequency, character and distribution of ubiquitin and TDP-43 positive inclusions are consistent with changes seen in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U) (3). Within the hippocampal formation, there is pyramidal neuron loss with reactive gliosis, somewhat out of proportion to the tangle pathology. Interestingly, it has been suggested that hippocampal sclerosis is commonly associated with the inclusions that characterize FTLD-U (3). In addition there are Lewy bodies and Lewy neurites involving brainstem, pons and medulla, but not involving cortical regions. This distribution of Lewy body disease is that of stage 3 of 6 according to Braak and colleagues.

It's hard to believe it's been almost three years since my dad, Ed Ambrose, passed away. It doesn't seem that long – and yet it seems like forever. So much has changed in those three years yet their house seems to have been frozen in time. My brothers and I have been spending time clearing out their Vineyard home (which is why I haven't posted in awhile) in anticipation of it's sale. Bob and I remarked the other day that it's been very much like an archeological dig. Much of these never-before-seen artifacts have been buried in corners of the attic, basement, or garage.

My father died after a long and winding road littered with lewy bodies and cortical atrophies. He was correctly diagnosed by the first doctor we met at Brigham & Womens Hospital – before there was an acronym for the disease. We spent many more years trying to disprove the many doctors and test scans, trying different remedies, medications, and procedures – including putting a shunt in the back of my father's skull to drain his excess brain fluid.

Dementia is the long, sad goodbye. It gives you time to get used to the idea that this person you love is leaving you. It doesn't make it easier when they finally do, but it gives you months and years of grieving prior to their death, very different than the grieving one does when someone dies suddenly and you're not prepared (at least for me). It's not easier, or harder, than the more sudden and painful death my mother experienced from cancer. Just different. In the end, the very end, it was actually very similar. Both their bodies betrayed them, leaving them breathless.

Dementia has a strange way of sneaking up on you too. How do you distinguish whether one's behavior is due to the subtleties of growing older or that of a terminal illness? With my father's type of dementia, it wasn't forgetfulness that we noticed first. It was a personality change. My father fell on the ice in his front yard and decided he wanted to move. To Hawaii. And if my mother, Nancy, didn't agree, he would go without her and she would be the one leaving him.

It took a family intervention, and a three-month trip for both of them to Hawaii, before my dad realized "something" was wrong. He came back from Hawaii a different man. He was less optimistic and more reserved. He slept a lot more. And he started talking less too, whether it was a fear of saying the wrong thing or just the fact that he couldn't find the right word, or possibly put all his words together in a way that made sense. He became the more silent partner in the marriage. No more retelling the same old stories, over and over again. Though I used to roll my eyes when he started on one of those stories, I began to wish he could tell them to me one more time.

In the later years of my dad's illness, my mother kept a diary of my dad's daily (mostly evening) activities. I found many of these after she died, and they are incredibly sad to read. She originally did this at my request, not only to prove she wasn't crazy, but to give me a reprieve from hearing these soap operas on a daily basis. These episodes were truly depressing, even just listening to them. I actually think it kept her sane, knowing that if it were on paper, she could prove to others she wasn't over-reacting, and that she was right, after all.

My mother and I believed my father was sick when no one else did, mostly because we saw him more often than anyone else. We wanted to believe that he was fine, and to be optimistic that he could be cured with a pill, but we were not the optimists in the family.

My father's ancestors are known to be long-lived, so he always thought he would live to be 100. Actually, my dad was quite healthy, and if it weren't for complications due to dementia, he might have reached that goal. He still has two aunts living in Norway, nearing 100, Aunt Pauline and Clara. And here's a photo of my dad visiting one of his Norwegian aunts, Gina Cunningham, who lived to be 108 years old in a nursing home outside San Francisco.

The memory tests my father took in the neurologist's office, while my mother and I watched, were also emotionally painful to watch. I remember thinking they were so tough that I would have trouble taking them. The doctor would ask a simple question that my father should know, but often didn't. I can still, to this day, see him look to me, with questions in his eyes, as if I could telepathically send him the answer. I had never felt so needed by him. At least not until he entered the various nursing homes, or his multiple trips to the geriatric psych ward.

Just the other day my brother Bob found an old phone in my parent's basement and plugged it in. It is the kind with the answering machine built-in (which I still like to use, actually). On it was a recording from 1996 of the three of us talking about my dad's Apple computer. Bob was advising my dad and me about adding RAM to my dad's computer. So there was my dad's voice, speaking about computers for three minutes, at a time when he was still normal.

I was determined to have a correct diagnosis of his dementia and had wanted to get a brain autopsy after his death. With my family's permission, we donated my father's brain to Mass General for research, after which they sent us these autopsy results, part of which I've shared here. I know that my father would have approved of this, as he favored knowledge above everything else in life. I hope in some small little way that my father has helped find a cure for this insidious disease.