Its Alice’s (Julianne Moore) 50th birthday party at a fancy restaurant. She is there with her husband (Alec Baldwin) and children. Her daughter Lydia is unable to come due to an audition.
Alice is waiting to be introduced at UCLA as a guest speaker in a Linguistics class. She is world renowned in her field. She starts her talk on how babies learn to speak and past tense irregular verbs. Suddenly, she forgets what she’s saying and seems to just lose her train of thought.
Later she’s in the car playing words with friends. She goes to visit her daughter Lydia (Kristen Stewart) and they go out to eat. Lydia talks about her career as an actress and Alice tries to talk her out of it and back to going to college.
Alice comes home to an empty house, (she lives in NYC) and decides to go for a jog. She suddenly stops and forgets where she is. She seems upset and tries to compose herself. After a few minutes she remembers where she is and heads home. Her husband is there and she’s upset that he is helping fund their daughter’s theater company.
Alice goes to the doctor and tells him about her memory problems. He does some memory exercises and asks her about her parents. She does well except for one test. She thinks she has a brain tumor and he decides to do a precautionary MRI.
Alice is at home preparing Christmas dinner and doing some practice memory exercises herself. As people arrive she forgets little things like the name of a kitchen utensil. Lydia and her siblings come home also all making small talk. During dinner Alice reintroduces herself to her son’s girlfriend Jenny, confusing her, as they’ve already met.
She goes back to the doctor who says her MRI is fine but he wants to do a PET scan to check for early onset Alzheimer’s Disease due to her memory issues. Going on with their daily lives, Alice is very upset over the possibility of having the disease. She decides to tell her husband what’s going on. He’s in complete denial and she has a meltdown.
They go to the neurologist together and he gives them the bad news. He wants to test her and her children for the gene. They tell the kids and they take the test. Her oldest daughter Anna (Kate Bosworth) is positive (meaning she will eventually develop the disease). She has been going for fertility treatments and is happy that at least they can test the embryos for the gene.
Alice sits with her boss and they read reviews from her students who say bad things about her and the course. She tells her boss she has a medical issue and comes clean. She wants to stay as long as possible in the department.
After a jog she, goes to Pink Berry for frozen yogurt by herself and when she gets home John is upset because she forgot about important dinner plans. He was worried about her.
Alice goes to check out a nursing home for the elderly with Alzheimer’s under the pretense of worrying about her parents. She writes a note to herself in her phone with basic questions such as what is the name of her oldest daughter, and then records herself talking to herself (to be watched later) telling herself to swallow a bottle of pills to commit suicide. In the cell phone note it says to watch that video when she can no longer answer the basic questions.
She now has to wear a bracelet that says memory impaired. She is let go from Columbia and she and John go to their beach house. They laugh and reminisce about their lives together. Later, she practices answering the questions on her phone. She is becoming increasingly forgetful, asking John repeatedly about when he is going on a conference and when Lydia is coming. They are supposed to go running but she cant remember where the bathroom is and wets her pants. She cries as she no longer remembers where she is.
John has to leave for a conference so Lydia comes to stay with her. Alice tells her a list of things she wants to see before she can’t anymore, including Lydia going to college. She decides to read one of her plays that has to deal with AIDS it gives them something to talk about. While going through the plays though, she comes across Lydia’s journal and reads it, resulting in a fight.
Anna is pregnant with twins. She and Lydia get into a fight over Alice. Alice remembers that she fought with Lydia but doesn’t know what it was about. Lydia apologizes to her for snapping, even though Alice doesn’t know what shes talking about. They have a heart to heart about what Alice is going through.
They go to her play the next night and after the show when they go backstage Alice doesn’t recognize Lydia as her daughter. They go back to the doctor with concerns about the pace she is deteriorating. She can no longer remember what a highlighter is for example. She gives a speech about the disease to the Alzheimer’s Association that her family is able to watch hoping for a cure.
John is offered a position at the Mayo Clinic in Minnesota. She wants him to delay the job for a year but he can’t take off a year for financial reasons. He also doesn’t want to take off a year and be at home with her watching her deteriorate. She tries to answer the questions on her phone and can no longer spell the month October. She wakes up in the middle of the night and goes to the kitchen, and is frantically looking for her phone. She takes everything out of the drawers and John goes to her she’s panicking because she doesn’t have her phone which goes off every morning at 8 to ask her the questions.
Anna goes to see her. Alice thinks she’s her sister at first. John finds her phone – it was in the freezer with the ice cube trays. Alice thinks she was only looking for it the night before but it had been a whole month. She can’t remember how to tie her shoes or what to do with toothpaste. John wakes her up in the morning to help her get dressed. They go to see Anna in the hospital as she just had the babies but her husband is afraid to let her hold them. Back at home they are all trying to figure out what to do. She has a carer now – Elena. Alice is skyping with Lydia and Elena isn’t there that day, leaving her all alone. She opens up the video she recorded of herself and hears the instructions about swallowing the pills. By the time she gets to her bedroom however she already forgets what the instructions were so she has to go back downstairs and watch it again until the time comes where she actually needs to bring the computer with her. As soon as she goes to take the pills Elena arrives and she drops them all, forgetting what she was even doing in the first place.
John and Alice go to Pink Berry. She can’t remember what flavor she usually orders and doesn’t recognize Columbia. Lydia has moved back home to NY to help take care of Alice while John leaves to take the job in Minnesota.
In the final scene, Lydia reads Alice a story (or monologue from a play?) and as she reads it Alice flashes back to happy times. Lydia asks Alice if she knew what it was about. Alice cannot speak well anymore, and mumbles that it was about love. They hug and we are to presume that Alice continues to deteriorate.